start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=1 article-no= start-page=100720 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dynamin 2 is involved in osteoblast migration by regulating the organization of F-actin en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Dynamin, a GTPase that regulates membrane dynamics, has recently been implicated in actin cytoskeletal remodeling. This study aimed to elucidate the role of dynamin in osteoblast migration by examining the effects of dynamin inhibition on the localization and organization of F-actin and dynamin 2 in MC3T3-E1 cells.
Methods: MC3T3-E1 cells were treated with dynamin inhibitors (Dyngo 4a and Dynole 34-2), and cell migration was assessed using a wound-healing assay. Fluorescent staining was performed to analyze the intracellular localization of F-actin and dynamin 2.
Results: Dynamin inhibition significantly reduced the migration of MC3T3-E1 cells. Fluorescence analysis revealed a marked decrease in the accumulation and colocalization of F-actin and dynamin 2 at the protrusion edge. Additionally, dynamin inhibition suppressed the formation of lamellipodia and stress fibers while promoting the appearance of abnormal F-actin clusters in the cytoplasm.
Conclusions: These findings suggest that dynamin plays an essential role in osteoblast migration by regulating actin cytoskeletal remodeling, particularly through the formation of lamellipodia and stress fibers. en-copyright= kn-copyright= en-aut-name=MoriyaTakumi en-aut-sei=Moriya en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SurongA. en-aut-sei=Surong en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TatsumiNanami en-aut-sei=Tatsumi en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakemotoFumiko en-aut-sei=Takemoto en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkamuraHirohiko en-aut-sei=Okamura en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IkegameMika en-aut-sei=Ikegame en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthodontics, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Dynamin kn-keyword=Dynamin en-keyword=Cell migration kn-keyword=Cell migration en-keyword=Osteoblasts kn-keyword=Osteoblasts en-keyword=F-actin kn-keyword=F-actin END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=19 article-no= start-page=9630 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Critical Requirement of Senescence-Associated CCN3 Expression in CD44-Positive Stem Cells for Osteoarthritis Progression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and subchondral bone remodeling. Previous studies have shown that cellular communication network factor 3 (CCN3) expression increases with age in cartilage, and its overexpression promotes OA-like changes by inducing senescence-associated secretory phenotypes. This study aimed to investigate the effect of Ccn3 knockout (KO) on OA development using a murine OA model. Destabilization of the medial meniscus (DMM) surgery was performed in wild-type (WT) and Ccn3-KO mice. Histological scoring and staining were used to assess cartilage degeneration and proteoglycan loss. Gene and protein expressions of catabolic enzyme (Mmp9), hypertrophic chondrocyte marker (Col10a1), senescence marker, and cyclin-dependent kinase inhibitor 1A (Cdkn1a) were evaluated. Single-cell RNA sequencing (scRNA-seq) data from WT and Sox9-deficient cartilage were reanalyzed to identify Ccn3+ progenitor populations. Immunofluorescence staining assessed CD44 and Ki67 expression in articular cartilage. The effects of Ccn3 knockdown on IL-1β-induced Mmp13 and Adamts5 expression in chondrocytes were examined in vitro. Ccn3 KO mice exhibited reduced cartilage degradation and catabolic gene expression compared with WT mice post-DMM. scRNA-seq revealed enriched Ccn3-Cd44 double-positive cells in osteoblast progenitor, synovial mesenchymal stem cell, and mesenchymal stem cell clusters. Immunofluorescence showed increased CCN3+/CD44+ cells in femoral and tibial cartilage and meniscus. Ki67+ cells were significantly increased in DMM-treated Ccn3 KO cartilage, mostly CD44+. In vitro Ccn3 knockdown attenuated IL-1β-induced Mmp13 and Adamts5 expressions in chondrocytes. Ccn3 contributes to OA pathogenesis by promoting matrix degradation, inducing hypertrophic changes, and restricting progenitor cell proliferation, highlighting Ccn3 as a potential therapeutic target for OA. en-copyright= kn-copyright= en-aut-name=HabumugishaJanvier en-aut-sei=Habumugisha en-aut-mei=Janvier kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkudaRyuichiro en-aut-sei=Okuda en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiroseKazuki en-aut-sei=Hirose en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuwaharaMiho en-aut-sei=Kuwahara en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HattoriTakako en-aut-sei=Hattori en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=articular kn-keyword=articular en-keyword=cartilage kn-keyword=cartilage en-keyword=mesenchymal stem cells kn-keyword=mesenchymal stem cells en-keyword=nephroblastoma overexpressed protein kn-keyword=nephroblastoma overexpressed protein en-keyword=osteoarthritis kn-keyword=osteoarthritis END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=166 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PEGylation of liposome-encapsulated midazolam does not improve the bioavailability of midazolam when administered orally en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Liposomes are closed vesicles made of the same phospholipid bilayer as biological membranes and are capable of containing drugs, and so they have been investigated as useful drug carriers for drug delivery. We previously developed liposome-encapsulated midazolam (LE-midazolam) for oral administration, but midazolam is metabolized in the liver, and for clinical use the encapsulation of the liposomes needed to be improved to increase the bioavailability of midazolam. The surfaces of pharmaceutical liposomes are generally coated with polyethylene glycol (PEGylation) because it prevents their capture by phagocytes and helps them to avoid the reticuloendothelial system. Therefore, we considered that PEGylation could reduce the metabolism of orally administered encapsulated midazolam in the liver.
Methods Midazolam solution, LE-midazolam solution, and PEGylated liposome-encapsulated midazolam (PEG-LE-midazolam) solution were prepared, and the characteristics of the liposomes in these solutions were evaluated. Furthermore, these solutions were orally administered to rabbits, and the resultant plasma midazolam concentrations were measured. The effects of the PEGylation of LE-midazolam on the plasma concentration and bioavailability of orally administered midazolam were also evaluated.
Results The PEG-LE-midazolam solution contained a higher percentage of larger liposomes than the LE-midazolam solution. The area under the concentration-time curve (AUC) of the LE-midazolam solution was significantly higher than that of the midazolam solution, but there was no difference between the AUC values of the PEG-LE-midazolam and midazolam solutions.
Conclusions These findings suggest that liposome encapsulation may reduce the first-pass effect following oral administration, but PEGylation is not expected to improve the bioavailability of orally administered midazolam. en-copyright= kn-copyright= en-aut-name=NishiokaYukiko en-aut-sei=Nishioka en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LuYanyin en-aut-sei=Lu en-aut-mei=Yanyin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiguchiHitoshi en-aut-sei=Higuchi en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeSaki en-aut-sei=Miyake en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimotoMaki en-aut-sei=Fujimoto en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Hamaoka-InoueMidori en-aut-sei=Hamaoka-Inoue en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanimuraHiroshi en-aut-sei=Tanimura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UjitaHitomi en-aut-sei=Ujita en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaShigeru en-aut-sei=Maeda en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyawakiTakuya en-aut-sei=Miyawaki en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=PEGylation kn-keyword=PEGylation en-keyword=Liposome kn-keyword=Liposome en-keyword=Midazolam kn-keyword=Midazolam en-keyword=Oral administration kn-keyword=Oral administration en-keyword=Bioavailability kn-keyword=Bioavailability END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=1 article-no= start-page=100718 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of Mycobacterium-derived plasmids for application in oral Actinomyces species en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Genetic manipulation tools are essential for elucidating the pathogenic mechanisms of microorganisms. Several species of Actinomyces, including A. israelii, are present in the oral cavity and they are the causative agents of actinomycosis. However, efficient gene-editing tools for these species have not yet been developed. In this study, the aim was to evaluate the introduction of foreign genes into Actinomyces using plasmids derived from Mycobacterium, which belong to the same class as Actinomycetes.
Methods: A truncated derivative of pYT923, pYT923S, which contains the replication origin of the M. scrofulaceum plasmid pMSC262 was constructed and introduced into A. israelii by electrotransformation.
Results: pYT923S was successfully introduced into A. israelii. The transformation efficiency of A. israelii was approximately 7–66 CFU/μg of DNA, and all transformed colonies harbored pYT923S. The plasmid recovered from A. israelii replicated in Escherichia coli.
Conclusions: pYT923S was introduced into and maintained within A. israelii. Therefore, the pYT923S vector represents a useful genetic tool for Actinomyces and it is expected to facilitate future studies on the biology and pathogenicity of Actinomyces. en-copyright= kn-copyright= en-aut-name=OharaSakiko en-aut-sei=Ohara en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShengYijuan en-aut-sei=Sheng en-aut-mei=Yijuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiyaYuki en-aut-sei=Nishiya en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TosaIkue en-aut-sei=Tosa en-aut-mei=Ikue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ArimuraYuki en-aut-sei=Arimura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MeseHiroshi en-aut-sei=Mese en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OharaNaoko en-aut-sei=Ohara en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Dentistry and Oral Surgery, Fukuyama City Hospital kn-affil= affil-num=8 en-affil=Department of Operative Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Actinomyces kn-keyword=Actinomyces en-keyword=Plasmid kn-keyword=Plasmid en-keyword=Shuttle vector kn-keyword=Shuttle vector en-keyword=Transformation kn-keyword=Transformation END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=6 article-no= start-page=1100 end-page=1111 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relation between obesity and health disorders as revealed by the J-ORBIT clinical information collection system directly linked to electronic medical records (J-ORBIT 1) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims/Introduction: Obesity triggers various health disorders, but information on these disorders in real-world settings remains limited. To address this knowledge gap, we developed a database directly linked to electronic medical records (EMRs). We here present the baseline data for this database, designated Japan Obesity Research Based on electronIc healTh Records (J-ORBIT).
Materials and Methods: Individuals with obesity disease diagnosed according to the criteria of the Japan Society for the Study of Obesity were registered in J-ORBIT from seven medical centers in Japan. We analyzed the relationship between body mass index (BMI), clinical characteristics, and the prevalence of obesity-related health disorders in this cohort.
Results: Data were obtained from 1,169 individuals, with a mean (±SD) age of 56.9 ± 15.3 years and a BMI of 31.4 ± 6.1 kg/m2. The prevalence of health disorders varied substantially across BMI categories, with a higher BMI being associated with an increased prevalence of hyperuricemia or gout, obstructive sleep apnea syndrome or obesity hypoventilation syndrome, musculoskeletal disorders, and obesity-related kidney disease, as well as with a higher frequency of both a family history of obesity and of a history of childhood obesity. Among individuals with a BMI of ≥25 kg/m2, the prevalence of hypertension and dyslipidemia did not increase with BMI, whereas that of glucose intolerance decreased with increasing BMI.
Conclusions: The J-ORBIT system, which collects clinical data in real time directly from EMRs, has the potential to provide insight into obesity and its associated health conditions, thereby contributing to improved care of affected individuals. en-copyright= kn-copyright= en-aut-name=NishikageSeiji en-aut-sei=Nishikage en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirotaYushi en-aut-sei=Hirota en-aut-mei=Yushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakagawaYasushi en-aut-sei=Nakagawa en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiiMasamichi en-aut-sei=Ishii en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhsugiMitsuru en-aut-sei=Ohsugi en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaedaEiichi en-aut-sei=Maeda en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshimuraKai en-aut-sei=Yoshimura en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoAkane en-aut-sei=Yamamoto en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakayoshiTomofumi en-aut-sei=Takayoshi en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatoTakehiro en-aut-sei=Kato en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YabeDaisuke en-aut-sei=Yabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsuhisaMunehide en-aut-sei=Matsuhisa en-aut-mei=Munehide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujitaYukihiro en-aut-sei=Fujita en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KumeShinji en-aut-sei=Kume en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaegawaHiroshi en-aut-sei=Maegawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MiyakeKana en-aut-sei=Miyake en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShojimaNobuhiro en-aut-sei=Shojima en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamauchiToshimasa en-aut-sei=Yamauchi en-aut-mei=Toshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YokoteKoutaro en-aut-sei=Yokote en-aut-mei=Koutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=UekiKohjiro en-aut-sei=Ueki en-aut-mei=Kohjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MiyoKengo en-aut-sei=Miyo en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OgawaWataru en-aut-sei=Ogawa en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Center for Medical Informatics Intelligence, National Center for Global Health and Medicine kn-affil= affil-num=5 en-affil=Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine kn-affil= affil-num=6 en-affil=Division of Medical Informatics, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=17 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=18 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Diabetes and Metabolic Disease, The University of Tokyo Graduate School of Medicine kn-affil= affil-num=21 en-affil=Chiba University kn-affil= affil-num=22 en-affil=Diabetes Research Center, Research Institute, National Center for Global Health and Medicine kn-affil= affil-num=23 en-affil=Center for Medical Informatics Intelligence, National Center for Global Health and Medicine kn-affil= affil-num=24 en-affil=Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= en-keyword=Body mass index kn-keyword=Body mass index en-keyword=Electronic medical records kn-keyword=Electronic medical records en-keyword=Obesity kn-keyword=Obesity END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic ductal adenocarcinoma (PDAC)-associated pancreatic stellate cells (PSCs) promote PDAC tumor progression. Notably, PDAC tumors display enhanced macropinocytosis, resulting in enhanced uptake of extracellular particles, including nutrients and viruses. We previously demonstrated the therapeutic potential of telomerase-specific oncolytic adenoviruses OBP-301 and p53-armed OBP-702 against human PDAC cells. However, it remains unclear whether macropinocytosis promotes the virus sensitivity of PDAC-associated PSCs. Here, we show that PSCs activated by human PDAC cells (Panc-1 and BxPC-3) exhibit enhanced sensitivity to wild-type and oncolytic adenoviruses via enhanced macropinocytosis. The virus sensitivity of PSCs was analyzed for the infectivity, replication, and cytopathic activity of wild-type and oncolytic adenoviruses. PDAC-associated PSCs were more sensitive to wild-type and oncolytic adenoviruses than were control PSCs; this sensitivity was mediated by activation of macropinocytosis. In three-dimensional (3D) culture models, p53-armed OBP-702 decreased the viability of PDAC-associated PSCs more strongly than did non-armed OBP-301, reflecting induction of p53-mediated apoptosis. Co-inoculation of PSCs enhanced the growth of PDAC tumors, an effect that was attenuated by OBP-702-mediated p53 activation in the tumor stroma. Our results suggest that p53-armed oncolytic adenovirus OBP-702 eliminates PDAC-associated PSCs via enhancement of macropinocytosis-mediated virus entry and induction of p53-mediated apoptosis. en-copyright= kn-copyright= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KajiwaraYoshinori en-aut-sei=Kajiwara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HashimotoNaoyuki en-aut-sei=Hashimoto en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiYosuke en-aut-sei=Takahashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KanoMitsunobu R. en-aut-sei=Kano en-aut-mei=Mitsunobu R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MasamuneAtsushi en-aut-sei=Masamune en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=15 en-affil=Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=16 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=127 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250315 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical predictors of extubation failure in postoperative critically ill patients: a post-hoc analysis of a multicenter prospective observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Postoperative patients constitute majority of critically ill patients, although factors predicting extubation failure in this group of patients remain unidentified. Aiming to propose clinical predictors of reintubation in postoperative patients, we conducted a post-hoc analysis of a multicenter prospective observational study.
Methods This study included postoperative critically ill patients who underwent mechanical ventilation for > 24 h and were extubated after a successful 30-min spontaneous breathing trial. The primary outcome was reintubation within 48 h after extubation, and clinical predictors for reintubation were investigated using logistic regression analyses.
Results Among the 355 included patients, 10.7% required reintubation. Multivariable logistic regression identified that the number of endotracheal suctioning episodes during the 24 h before extubation and underlying respiratory disease or pneumonia occurrence were significantly associated with reintubation (adjusted odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05–1.18, p < 0.001; adjusted OR 2.58, 95%CI 1.30–5.13, p = 0.007). The probability of reintubation was increased significantly with the higher frequency of endotracheal suctioning, as indicated by restricted cubic splines. Subgroup analysis showed that these predictors were consistently associated with reintubation regardless of the use of noninvasive respiratory support after extubation.
Conclusions Endotracheal suctioning frequency and respiratory complications were identified as independent predictors of reintubation. These readily obtainable predictors may aid in decision-making regarding the extubation of postoperative patients. en-copyright= kn-copyright= en-aut-name=HattoriJun en-aut-sei=Hattori en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaAiko en-aut-sei=Tanaka en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KosakaJunko en-aut-sei=Kosaka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiraoOsamu en-aut-sei=Hirao en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FurushimaNana en-aut-sei=Furushima en-aut-mei=Nana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MakiYuichi en-aut-sei=Maki en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KabataDaijiro en-aut-sei=Kabata en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchiyamaAkinori en-aut-sei=Uchiyama en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EgiMoritoki en-aut-sei=Egi en-aut-mei=Moritoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MizobuchiSatoshi en-aut-sei=Mizobuchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KotakeYoshifumi en-aut-sei=Kotake en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShintaniAyumi en-aut-sei=Shintani en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KoyamaYukiko en-aut-sei=Koyama en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YoshidaTakeshi en-aut-sei=Yoshida en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujinoYuji en-aut-sei=Fujino en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Faculty of Medicine, Osaka University kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Anesthesiology, Osaka General Medical Center kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Intensive Care Medicine, Kobe University Hospital kn-affil= affil-num=6 en-affil=Department of Anesthesiology, Toho University Ohashi Medical Center kn-affil= affil-num=7 en-affil=Center for Mathematical and Data Science, Kobe University kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Anesthesia, Kyoto University Hospital kn-affil= affil-num=10 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Anesthesiology and Intensive Care Medicine, Kobe University Hospital kn-affil= affil-num=12 en-affil=Department of Anesthesiology, Toho University Ohashi Medical Center kn-affil= affil-num=13 en-affil=Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=14 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine kn-affil= en-keyword=Reintubation kn-keyword=Reintubation en-keyword=Extubation failure kn-keyword=Extubation failure en-keyword=Endotracheal suctioning kn-keyword=Endotracheal suctioning en-keyword=Postoperative patient kn-keyword=Postoperative patient en-keyword=Clinical predictor kn-keyword=Clinical predictor en-keyword=Critical care kn-keyword=Critical care END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=DSOK-0011 Potentially Regulates Circadian Misalignment and Affects Gut Microbiota Composition in Activity-Based Anorexia Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Anorexia nervosa (AN) is a metabolic-psychiatric disorder characterized by severe weight loss, hypercortisolemia, and hypothalamic–pituitary–adrenal (HPA) axis activation. In this study, we investigated the effect of inhibiting cortisol regeneration via the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on the pathophysiology of AN.
Method: Female C57BL/6J mice underwent a 7-day activity-based anorexia (ABA) paradigm, involving 3 h daily feeding and free access to wheels, until 25% body weight loss or experiment completion. Mice were orally treated once daily with a potent 11β-HSD1 inhibitor, DSOK-0011, or vehicle. Body weight, food intake, and activity transitions were recorded; plasma corticosterone and cholesterol levels were measured using a fluorometric assay; gut microbiota were analyzed using 16S rRNA sequencing; and hippocampal glial cells were analyzed using immunohistochemistry.
Results: DSOK-0011-treated mice exhibited a modest but significant increase in postprandial wheel-running activity compared to baseline (4–5 p.m., p = 0.018; 5–6 p.m., p = 0.043), whereas vehicle-treated mice showed higher preprandial activity (9–10 a.m., p = 0.0229). Gut microbiota analysis revealed increased alpha diversity in ABA mice, with a specific enrichment of the Lachnospiraceae family in the DSOK-0011 group. However, DSOK-0011 did not significantly affect body weight, food intake, corticosterone, and lipid levels, or hippocampal glial cell populations.
Conclusion: Inhibition of 11β-HSD1 by DSOK-0011 was associated with microbiota alterations and subtle shifts in activity timing under energy-deficient conditions. These findings suggest that peripheral glucocorticoid metabolism may influence microbial and behavioral responses in the ABA model, although its metabolic impact appears limited in the acute phase. en-copyright= kn-copyright= en-aut-name=KawaiHiroki en-aut-sei=Kawai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaNanami en-aut-sei=Wada en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyazakiKenji en-aut-sei=Miyazaki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTaro en-aut-sei=Kato en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriuchiYoshihiro en-aut-sei=Horiuchi en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KiriiHiroshi en-aut-sei=Kirii en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NguyenHoang Duy en-aut-sei=Nguyen en-aut-mei=Hoang Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HinotsuKenji en-aut-sei=Hinotsu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhyaYoshio en-aut-sei=Ohya en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsadaTakahiro en-aut-sei=Asada en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YokodeAkiyoshi en-aut-sei=Yokode en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkahisaYuko en-aut-sei=Okahisa en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyazakiHaruko en-aut-sei=Miyazaki en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=5 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=6 en-affil=Sumitomo Pharma Co. Ltd kn-affil= affil-num=7 en-affil=Department of Animal Applied Microbiology, Okayama University Graduate School of Environmental, Life, Natural Science and Technology kn-affil= affil-num=8 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=11β-HSD1 kn-keyword=11β-HSD1 en-keyword=activity-based anorexia kn-keyword=activity-based anorexia en-keyword=anorexia nervosa kn-keyword=anorexia nervosa en-keyword=corticosterone kn-keyword=corticosterone en-keyword=eating disorders kn-keyword=eating disorders en-keyword=microbiota kn-keyword=microbiota END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=1 article-no= start-page=22 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protective impact of landiolol against acute lung injury following hemorrhagic shock and resuscitation in rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation, leading to acute lung injury (ALI). Notably, blocking β1 receptors can lead to organ protection through anti‑inflammatory and anti‑apoptotic effects. Additionally, although the β1 receptor pathway is blocked by the β1 blocker, the β2 receptor pathway may be preserved and activate the 5' adenosine monophosphate‑activated protein kinase (AMPK) pathway. The present study aimed to examine whether administration of the β1 blocker landiolol could achieve lung protection in a model of HSR‑ALI, alongside improvements in inflammation and apoptosis. Male Sprague‑Dawley rats underwent hemorrhage keeping their mean arterial pressure at 30 mmHg for 1 h. Resuscitation by reinfusion was initiated to restore blood pressure to pre‑hemorrhage levels for >15 min, followed by a 45‑min stabilization period to create the HSR‑ALI model. Landiolol (100 mg/kg/min) or saline was continuously administered after resuscitation. The lung tissues, which were collected for assessing inflammation and apoptosis‑related damage, underwent analyses, including histological examination, neutrophil count, assessment of lung wet/dry weight ratio, detection of the mRNA levels of tumor necrosis factor‑α (TNF‑α) and inducible nitric oxide synthase (iNOS), identification of terminal deoxynucleotidyl transferase dUTP nick‑end labeling (TUNEL)‑positive cells, and evaluation of caspase‑3 expression. In addition, phosphorylated AMPKα (pAMPKα) expression was tested via western blotting. Compared with the HSR/saline group, the HSR/landiolol group demonstrated a reduction in lung tissue damage score, and significant reductions in neutrophil count, lung wet/dry weight ratio, lung TNF‑α and iNOS mRNA levels, TUNEL‑positive cells and cleaved caspase‑3 expression. Furthermore, landiolol administration following HSR treatment increased pAMPKα expression. No significant hypotension occurred between the HSR/landiolol and HSR/saline groups; and blood loss did not differ significantly between the groups. In conclusion, landiolol administration after HSR reduced lung inflammation and apoptosis, suggesting a potential improvement in tissue damage. Furthermore, pAMPKα activation in the HSR/landiolol group may be the mechanism underlying the pulmonary protective effects of landiolol. en-copyright= kn-copyright= en-aut-name=SakamotoRisa en-aut-sei=Sakamoto en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimizuHiroko en-aut-sei=Shimizu en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraRyu en-aut-sei=Nakamura en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LuYifu en-aut-sei=Lu en-aut-mei=Yifu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiYaqiang en-aut-sei=Li en-aut-mei=Yaqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriEmiko en-aut-sei=Omori en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiToru en-aut-sei=Takahashi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=4 en-affil=Department of Human Anatomy, Shantou University Medical College kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Anesthesiology, Okayama Saidaiji Hospital kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=HSR kn-keyword=HSR en-keyword=lung injury kn-keyword=lung injury en-keyword=landiolol kn-keyword=landiolol en-keyword=β1 blocker kn-keyword=β1 blocker en-keyword=inflammation kn-keyword=inflammation en-keyword=apoptosis kn-keyword=apoptosis END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=59 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Venous air embolism induced by burr hole drilling before dural incision in craniotomy: two case reports en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Venous air embolism (VAE) is a rare but potentially fatal complication in neurosurgery typically caused by injury to dura mater, especially venous sinuses, during craniotomy. We report two cases of VAE that occurred before dural incision.
Case presentation: Both patients underwent craniotomy under general anesthesia in a head-up position. Hemodynamic and respiratory deterioration occurred during or immediately after burr hole drilling with abnormal vital signs and transesophageal echocardiography findings, raising suspicion for VAE. Immediate management, including surgical field protection and cardiopulmonary support, stabilized the patients’ conditions. The procedure was subsequently discontinued in case 1 and modified to limited resection in case 2. Postoperative computed tomography revealed intracranial venous air within the internal jugular vein, cavernous sinus, and diploic veins.
Conclusion: These cases highlight that VAE can occur even before dural incision. Vigilant intraoperative monitoring and prompt intervention are essential for preventing potentially fatal outcomes. en-copyright= kn-copyright= en-aut-name=MotoiYohei en-aut-sei=Motoi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkaharaShuji en-aut-sei=Okahara en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniMakiko en-aut-sei=Tani en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboiNobushige en-aut-sei=Tsuboi en-aut-mei=Nobushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neurosurgery, Okayama Red Cross Hospital kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= en-keyword=Venous air embolism kn-keyword=Venous air embolism en-keyword=Transesophageal echocardiography kn-keyword=Transesophageal echocardiography en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Diploic veins kn-keyword=Diploic veins en-keyword=Emissary veins kn-keyword=Emissary veins en-keyword=Burr hole drilling kn-keyword=Burr hole drilling en-keyword=Case report kn-keyword=Case report END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250909 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Status of Continuous Renal Replacement Therapy in Japanese Intensive Care Units: A Multicenter Retrospective Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Continuous renal replacement therapy (CRRT) is often performed for critically ill patients in intensive care units (ICUs), but its optimal indication and settings have yet to be determined. Thus, we aimed to describe the current status of CRRT in Japan through a multicenter retrospective observational study. Methods: Adult ICU patients receiving CRRT at 18 tertiary hospitals in Japan (up to 100 patients from each hospital over the past year) were retrospectively enrolled. Patients receiving CRRT for <24 h or intermittent renal replacement therapy together with CRRT were excluded. The primary outcomes were the temporal changes in the electrolyte levels, acid-base balance, and uremia-related small solute concentrations. The secondary outcomes included potassium (K) and phosphate (P) supplementations during CRRT. Results: Altogether, 1,045 patients were enrolled. The median CRRT duration and dose were 4.4 days and 17.3 mL/kg/h, respectively. The electrolyte levels, acid-base balance, and uremia-related small solute concentrations returned to normal by day 4 of treatment. A total of 732 (70.0%) patients received K supplementation, and only a few patients had hypokalemia until day 5. Moreover, 414 (39.6%) patients received P supplementation, and approximately 30%–50% of the patients had hypophosphatemia until day 5. Conclusion: The CRRT dose in Japan was lower than that was recommended by the Kidney Disease: Improving Global Outcomes guideline. The electrolyte level abnormalities and acid-base imbalances of the studied patients were improved within 72–96 h of CRRT. Contrarily, K and P supplementations were common, indicating that the current CRRT solutions need to be modified. en-copyright= kn-copyright= en-aut-name=NakanoHidehiko en-aut-sei=Nakano en-aut-mei=Hidehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InokuchiRyota en-aut-sei=Inokuchi en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueYutaro en-aut-sei=Inoue en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekinoMotohiro en-aut-sei=Sekino en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakihanaYasuyuki en-aut-sei=Kakihana en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HattoriNoriyuki en-aut-sei=Hattori en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyazakiMariko en-aut-sei=Miyazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TokuhiraNatsuko en-aut-sei=Tokuhira en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujitaniShigeki en-aut-sei=Fujitani en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TodaYuichiro en-aut-sei=Toda en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhchiYoshifumi en-aut-sei=Ohchi en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IchibaShingo en-aut-sei=Ichiba en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MasudaYoshiki en-aut-sei=Masuda en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishidaOsamu en-aut-sei=Nishida en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=AbeTakaya en-aut-sei=Abe en-aut-mei=Takaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MoriguchiTakeshi en-aut-sei=Moriguchi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SatohKasumi en-aut-sei=Satoh en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IdeiMasafumi en-aut-sei=Idei en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NagataHiromasa en-aut-sei=Nagata en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=DoiKent en-aut-sei=Doi en-aut-mei=Kent kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital kn-affil= affil-num=2 en-affil=Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital kn-affil= affil-num=3 en-affil=Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Nephrology, Tohoku University Hospital kn-affil= affil-num=8 en-affil=Department of Intensive Care, Osaka University Hospital kn-affil= affil-num=9 en-affil=Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine kn-affil= affil-num=10 en-affil=Department of Anesthesiology and Intensive Care Medicine, Kawasaki Medical School kn-affil= affil-num=11 en-affil=Department of Anesthesiology and Intensive Care, Oita University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Intensive Care Medicine, Tokyo Women’s Medical University kn-affil= affil-num=14 en-affil=Department of Intensive Care Medicine, Sapporo Medical University School of Medicine kn-affil= affil-num=15 en-affil=Department of Anesthesiology and Critical Care Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=16 en-affil=Department of Urology, Iwate Medical University kn-affil= affil-num=17 en-affil=Department of Emergency and Critical Care Medicine, University of Yamanashi Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Emergency and Critical Care Medicine, Akita University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Intensive Care Medicine, Yokohama City University kn-affil= affil-num=20 en-affil=Department of Anesthesiology, Keio University School of Medicine kn-affil= affil-num=21 en-affil=Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital kn-affil= en-keyword=Acute kidney injury kn-keyword=Acute kidney injury en-keyword=Renal failure kn-keyword=Renal failure en-keyword=Continuous renal replacement therapy kn-keyword=Continuous renal replacement therapy en-keyword=Electrolytes kn-keyword=Electrolytes END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=2 article-no= start-page=273 end-page=281 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=T2 high-signal-intensity zone of the spinal cord dorsal horn in patients treated with spinal cord stimulation for herpes zoster-associated pain: a retrospective case–control study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose In patients with herpes zoster-associated pain (ZAP), magnetic resonance imaging (MRI) has revealed T2 high-signal intensity zones (MRI T2 HIZ) in the dorsal horn of the spinal cord, associated with postherpetic neuralgia (PHN). We retrospectively analyzed the relationship between PHN and MRI T2 HIZ in patients with refractory ZAP in the subacute phase who underwent temporary spinal cord stimulation therapy (tSCS).
Methods This single-center, case–control study included patients who underwent tSCS for refractory ZAP between 2010 and 2018. MRIs were re-assessed for the presence of T2 HIZ in the dorsal horn of the spinal cord. Patients were divided into T2 HIZ( +) and T2 HIZ(−) groups. Patients with a numerical rating score (NRS) ≥ 3 at the last visit were defined as PHN. The NRS values and the incidence rate of PHN were compared between the two groups.
Results Of the 67 cases extracted, 38 were included in the analysis: 22 in T2 HIZ( +) group and 16 in T2 HIZ(−) group. No significant differences were observed in background factors between the two groups. However, the T2 HIZ( +) group had a significantly higher NRS at the final visit (T2 HIZ( +):3.8 ± 2.1, T2 HIZ(−):1.4 ± 1.5; P < 0.05) and had significantly more patients with PHN than the T2 HIZ(−) group (T2 HIZ( +) vs. T2 HIZ(−), 15/22 (68%) vs. 3/16 (19%); odds ratio = 8.67; 95% confidence interval, 1.7–63.3).
Conclusion T2HIZ is detected in more than half of refractory ZAP, and pain is more likely to remain after tSCS treatment in the T2HIZ( +) group. en-copyright= kn-copyright= en-aut-name=ArakawaKyosuke en-aut-sei=Arakawa en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaMasayuki en-aut-sei=Nakagawa en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AbeYoichiro en-aut-sei=Abe en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pain Management Clinic, NTT Medical Center Tokyo kn-affil= affil-num=3 en-affil=Department of Pain Management Clinic, NTT Medical Center Tokyo kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Herpes zoster kn-keyword=Herpes zoster en-keyword=Magnetic resonance imaging kn-keyword=Magnetic resonance imaging en-keyword=Postherpetic neuralgia kn-keyword=Postherpetic neuralgia en-keyword=Refractory zoster-associated pain kn-keyword=Refractory zoster-associated pain en-keyword=Temporary spinal cord stimulation kn-keyword=Temporary spinal cord stimulation END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=436 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of Pericapsular Nerve Group (PENG) block in preoperative rehabilitation (Prehabilitation) for patients with femoral neck fractures: study protocol for a randomized, placebo-controlled, double-blinded trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Despite surgery intervention for femoral neck fractures is recommended within 48 h of admission, achieving timely surgery presents challenges for patients with severe comorbidities, or in resource-limited settings. Preoperative rehabilitation (prehabilitation) reduces bedridden time, enhances mobility, and improves postoperative outcomes for patients scheduled for hip arthroplasty due to femoral neck fractures. However, prehabilitation is hindered by insufficient pain control. The pericapsular nerve group (PENG) block provides effective analgesia while preserving motor function. We designed a study to assess the efficacy of PENG block in facilitating prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty.
Methods This prospective randomized placebo-controlled double-blinded trial aims to enroll 100 patients with Garden 3 or 4 femoral neck fractures who are scheduled for hip arthroplasty. Participants will be randomly assigned to receive a PENG block with 0.375% ropivacaine (PENG group) or with normal saline (placebo group) before the initial prehabilitation session. The prehabilitation program comprises five items: Bed-sitting, Edge-sitting, Stand-up, Maintaining-standing, and Wheelchair-transfer, performed with the assistance of a single physical therapist. The primary outcome is the percentage of patients completing the entire prehabilitation program. Secondary outcomes during the initial prehabilitation session are the achievement of each program item and the Numerical Rating Scale (NRS) pain score. Other secondary outcomes include intraoperative bleeding amounts, thromboembolic events during postoperative day 0 to 7, postoperative 3-day cumulative Cumulated Ambulation Score (CAS), and discharge destination. The postoperative outcomes will be compared between subgroups of patients undergoing surgery within 48 h of admission and those undergoing surgery more than 48 h of admission.
Discussion This is the first study aiming to assess the efficacy of PENG block in prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty. PENG block could be beneficial, especially for patients facing delayed surgery, providing a potential treatment option during the waiting period.
Trial registration Japan Registry of Clinical Trials, jRCT1031220294, registered on August 26, 2022. en-copyright= kn-copyright= en-aut-name=JinZhuan en-aut-sei=Jin en-aut-mei=Zhuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiyamaDaisuke en-aut-sei=Sugiyama en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HigoFumiya en-aut-sei=Higo en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirataTakahiro en-aut-sei=Hirata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiOsamu en-aut-sei=Kobayashi en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UedaKenichi en-aut-sei=Ueda en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=3 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=5 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= en-keyword=Femoral neck fracture kn-keyword=Femoral neck fracture en-keyword=Hip fracture kn-keyword=Hip fracture en-keyword=PENG block kn-keyword=PENG block en-keyword=Pericapsular nerve group block kn-keyword=Pericapsular nerve group block en-keyword=Prehabilitation kn-keyword=Prehabilitation en-keyword=Preoperative mobilization kn-keyword=Preoperative mobilization en-keyword=Preoperative rehabilitation kn-keyword=Preoperative rehabilitation en-keyword=Randomized controlled trial kn-keyword=Randomized controlled trial en-keyword=Study protocol kn-keyword=Study protocol END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=565 end-page=569 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utilization of the pericapsular nerve group block in preoperative rehabilitation of patients with femoral neck fractures -a case series- en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Elderly patients with femoral neck fractures, particularly those with severe comorbidities or living in regions with limited medical resources, may experience delays in surgical treatment. Although the benefits of preoperative rehabilitation (prehabilitation) in hip arthroplasty have been reported, pain management remains a challenge. The pericapsular nerve group (PENG) block, known for its exceptional analgesic effect and motor function preservation, may be a promising intervention during prehabilitation in these patients.
Case: We enrolled ten patients with Garden classification 3–4 femoral neck fractures scheduled for hip arthroplasty. After receiving a PENG block with 20 ml of 0.375% ropivacaine, all patients underwent initial prehabilitation sessions comprising 9 mobility levels, ranging from bed-sitting to walking. One patient was excluded due to experiencing high blood pressure during prehabilitation. Six of the nine remaining patients (66.7%) were successfully transferred from bed to wheelchair.
Conclusions: The PENG block enhanced prehabilitation for patients with femoral neck fractures undergoing hip arthroplasty. en-copyright= kn-copyright= en-aut-name=JinZhuan en-aut-sei=Jin en-aut-mei=Zhuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiyamaDaisuke en-aut-sei=Sugiyama en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HigoFumiya en-aut-sei=Higo en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirataTakahiro en-aut-sei=Hirata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiOsamu en-aut-sei=Kobayashi en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UedaKenichi en-aut-sei=Ueda en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=3 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation, Kameda Medical Center kn-affil= affil-num=5 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Anesthesiology, Kameda Medical Center kn-affil= en-keyword=Conduction anesthesia kn-keyword=Conduction anesthesia en-keyword=Femoral neck fractures kn-keyword=Femoral neck fractures en-keyword=Hip fractures kn-keyword=Hip fractures en-keyword=Nerve block kn-keyword=Nerve block en-keyword=Prehabilitation kn-keyword=Prehabilitation en-keyword=Preoperative exercise kn-keyword=Preoperative exercise en-keyword=Preoperative rehabilitation kn-keyword=Preoperative rehabilitation en-keyword=Regional anesthesia kn-keyword=Regional anesthesia END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=38590 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oncolytic adenoviruses replicate selectively in tumor cells and induce immunogenic cell death, but predictive biomarkers for early therapeutic response are lacking. This study evaluated extracellular vesicle-encapsulated adenoviral E1A-DNA (EV-E1A-DNA) as a minimally invasive biomarker for monitoring responses to telomerase-specific oncolytic adenoviruses OBP-301 and OBP-502. EVs were isolated from human and murine cancer cell lines and from the serum of treated mice using ultracentrifugation. EV-associated E1A-DNA levels were measured by quantitative polymerase chain reaction and found to correlate with cytotoxicity in vitro and tumor regression in vivo. In xenograft models, serum EV-E1A-DNA levels at 2 days post-treatment showed strong correlations with final tumor volume and survival, supporting their utility as an early predictive biomarker. In immunocompetent mice pre-immunized with wild-type adenovirus, free viral DNA was undetectable in serum due to neutralizing antibodies, whereas EV-E1A-DNA remained detectable. This “stealth effect” indicates that EVs protect viral components from immune clearance. These results demonstrate that EV-E1A-DNA is a sensitive and virus-specific biomarker that enables early assessment of therapeutic efficacy, even in the presence of antiviral immunity. This strategy offers a promising liquid biopsy approach for personalized monitoring of oncolytic virotherapy and may be applicable to other virus-based therapies. en-copyright= kn-copyright= en-aut-name=YagiChiaki en-aut-sei=Yagi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HanzawaShunya en-aut-sei=Hanzawa en-aut-mei=Shunya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KadowakiDaisuke en-aut-sei=Kadowaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakamotoMasaki en-aut-sei=Sakamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamadaYuki en-aut-sei=Hamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoRyoma en-aut-sei=Sugimoto en-aut-mei=Ryoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhtaniTomoko en-aut-sei=Ohtani en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KumonKento en-aut-sei=Kumon en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Oncolytic adenovirus kn-keyword=Oncolytic adenovirus en-keyword=Extracellular vesicle kn-keyword=Extracellular vesicle en-keyword=Liquid biopsy kn-keyword=Liquid biopsy en-keyword=Predictive biomarker kn-keyword=Predictive biomarker en-keyword=Stealth effect kn-keyword=Stealth effect END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gemcitabine-induced neutrophil extracellular traps via interleukin-8-CXCR1/2 pathway promote chemoresistance in pancreatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, and chemoresistance poses a significant challenge in its treatment. Neutrophil extracellular traps (NETs) have emerged as key players in the tumour microenvironment, but their role in chemoresistance remains unclear.
Methods: We investigated the involvement of NETs in PDAC chemoresistance using patient tumour samples, in vitro assays with gemcitabine (GEM)-treated PDAC cells, and in vivo mouse models. We evaluated cytokine production, NET formation and tumour response to GEM, with or without the CXCR1/2 inhibitor navarixin.
Results: NETs are significantly accumulated in the tumours of PDAC patients exhibiting poor response to chemotherapy. GEM-treated PDAC cells secrete pro-inflammatory cytokines such as interleukin-8 (IL-8). IL-8 promote the formation of chemotherapy-induced NETs (chemoNETosis) through activation of CXCR 1/2 on neutrophils. Importantly, treatment with navarixin significantly suppressed chemoNETosis, restored sensitivity to GEM, and significantly reduced tumour growth in vivo.
Conclusions: Our findings reveal that NETs contribute to chemoresistance in PDAC and that IL-8–mediated chemoNETosis plays a pivotal role in this process. Inhibition of CXCR1/2-mediated NET formation enhances the efficacy of GEM. This approach may represent a promising therapeutic strategy for overcoming chemoresistance in PDAC. These results support further clinical investigation of anti-NETs therapies. en-copyright= kn-copyright= en-aut-name=NogiShohei en-aut-sei=Nogi en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniguchiAtsuki en-aut-sei=Taniguchi en-aut-mei=Atsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YagiTomohiko en-aut-sei=Yagi en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=27684 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250729 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The significance of adding posterior decompression to spine stabilization in metastatic spinal surgery: a multicenter prospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The usefulness of spine stabilization for treating metastatic spinal tumors with tumor-induced instability has been reported. However, no reports have prospectively evaluated the effectiveness of adding posterior decompression to stabilization surgery for improving symptoms. This multicenter prospective study aimed to determine whether adding posterior decompression to spine stabilization surgery for metastatic spinal tumors affects postoperative outcomes and complications. A total of 263 patients who underwent spine stabilization with (n = 189) or without (n = 74) decompression were analyzed. Patient demographics, the Spinal Instability Neoplastic Score (SINS), and the Epidural Spinal Cord Compression (ESCC) score were recorded. The outcomes were assessed preoperatively and at 1 and 6 months postoperatively in terms of neurological status, the Barthel Index, the EQ-5D-5 L, and the visual analog scale (VAS). Decompression was primarily performed in patients with severe neurological deficits and high-grade ESCC. Both groups showed postoperative improvement. Propensity score matching was applied to adjust for baseline differences. After matching, there were no significant differences in functional improvement between the decompression and nondecompression groups, and the complication rates were comparable. In matched patients presenting primarily with spinal instability and pain, the addition of decompression did not appear to confer a significant functional benefit within 6 months postoperatively. en-copyright= kn-copyright= en-aut-name=TominagaHiroyuki en-aut-sei=Tominaga en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawamuraIchiro en-aut-sei=Kawamura en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimadaHirofumi en-aut-sei=Shimada en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiHiromi en-aut-sei=Sasaki en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniguchiNoboru en-aut-sei=Taniguchi en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShirataniYuki en-aut-sei=Shiratani en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzukiAkinobu en-aut-sei=Suzuki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TeraiHidetomi en-aut-sei=Terai en-aut-mei=Hidetomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimizuTakaki en-aut-sei=Shimizu en-aut-mei=Takaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KakutaniKenichiro en-aut-sei=Kakutani en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KandaYutaro en-aut-sei=Kanda en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IshiharaMasayuki en-aut-sei=Ishihara en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=PakuMasaaki en-aut-sei=Paku en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakahashiYohei en-aut-sei=Takahashi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FunayamaToru en-aut-sei=Funayama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiuraKousei en-aut-sei=Miura en-aut-mei=Kousei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShirasawaEiki en-aut-sei=Shirasawa en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=InoueHirokazu en-aut-sei=Inoue en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KimuraAtsushi en-aut-sei=Kimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IimuraTakuya en-aut-sei=Iimura en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MoridairaHiroshi en-aut-sei=Moridaira en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=NakajimaHideaki en-aut-sei=Nakajima en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=WatanabeShuji en-aut-sei=Watanabe en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=AkedaKoji en-aut-sei=Akeda en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=TakegamiNorihiko en-aut-sei=Takegami en-aut-mei=Norihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=NakanishiKazuo en-aut-sei=Nakanishi en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=SawadaHirokatsu en-aut-sei=Sawada en-aut-mei=Hirokatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MatsumotoKoji en-aut-sei=Matsumoto en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=FunabaMasahiro en-aut-sei=Funaba en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SuzukiHidenori en-aut-sei=Suzuki en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=FunaoHaruki en-aut-sei=Funao en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=OshigiriTsutomu en-aut-sei=Oshigiri en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=HiraiTakashi en-aut-sei=Hirai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=OtsukiBungo en-aut-sei=Otsuki en-aut-mei=Bungo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=KobayakawaKazu en-aut-sei=Kobayakawa en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=ManabeHiroaki en-aut-sei=Manabe en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=TanishimaShinji en-aut-sei=Tanishima en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=HashimotoKo en-aut-sei=Hashimoto en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=IwaiChizuo en-aut-sei=Iwai en-aut-mei=Chizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=YamabeDaisuke en-aut-sei=Yamabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=HiyamaAkihiko en-aut-sei=Hiyama en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SekiShoji en-aut-sei=Seki en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=GotoYuta en-aut-sei=Goto en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=MiyazakiMasashi en-aut-sei=Miyazaki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=WatanabeKazuyuki en-aut-sei=Watanabe en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=NakamaeToshio en-aut-sei=Nakamae en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=KaitoTakashi en-aut-sei=Kaito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=NakashimaHiroaki en-aut-sei=Nakashima en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=NagoshiNarihito en-aut-sei=Nagoshi en-aut-mei=Narihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=KatoSatoshi en-aut-sei=Kato en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=ImagamaShiro en-aut-sei=Imagama en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=WatanabeKota en-aut-sei=Watanabe en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=InoueGen en-aut-sei=Inoue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=FuruyaTakeo en-aut-sei=Furuya en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Osaka Metropolitan University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Osaka Metropolitan University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Kansai Medical University Hospital kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Kansai Medical University Hospital kn-affil= affil-num=14 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=15 en-affil=Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba kn-affil= affil-num=16 en-affil=Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=18 en-affil=Rehabilitation Center, Jichi Medical University Hospital kn-affil= affil-num=19 en-affil=Department of Orthopaedics, Jichi Medical University kn-affil= affil-num=20 en-affil=Department of Orthopaedic Surgery, Dokkyo Medical University kn-affil= affil-num=21 en-affil=Department of Orthopaedic Surgery, Dokkyo Medical University kn-affil= affil-num=22 en-affil=Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=23 en-affil=Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=24 en-affil=Department of Orthopaedic Surgery, Mie University Graduate School of Medicine kn-affil= affil-num=25 en-affil=Department of Orthopaedic Surgery, Mie University Graduate School of Medicine kn-affil= affil-num=26 en-affil=Department of Orthopaedic Surgery, Kawasaki Medical School kn-affil= affil-num=27 en-affil=Department of Orthopaedic Surgery, Nihon University School of Medicine kn-affil= affil-num=28 en-affil=Department of Orthopaedic Surgery, Nihon University School of Medicine kn-affil= affil-num=29 en-affil=Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine kn-affil= affil-num=30 en-affil=Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine kn-affil= affil-num=31 en-affil=Department of Orthopaedic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=32 en-affil=Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine kn-affil= affil-num=33 en-affil=Department of Orthopedic Surgery, Institute of Science Tokyo kn-affil= affil-num=34 en-affil=Department of Orthopaedic Surgery, Kyoto University Hospital kn-affil= affil-num=35 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=36 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=37 en-affil=Department of Orthopedics, Tokushima University kn-affil= affil-num=38 en-affil=Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=39 en-affil=Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=40 en-affil=Department of Orthopaedic Surgery, Gifu University Hospital kn-affil= affil-num=41 en-affil=Department of Orthopaedic Surgery, Iwate Medical University kn-affil= affil-num=42 en-affil=Department of Orthopaedic Surgery, Tokai University School of Medicine kn-affil= affil-num=43 en-affil=Department of Orthopaedic Surgery, University of Toyama kn-affil= affil-num=44 en-affil=Department of Orthopaedic Surgery, Nagoya City University kn-affil= affil-num=45 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=46 en-affil=Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine kn-affil= affil-num=47 en-affil=Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=48 en-affil=Department of Orthopedic Surgery, Osaka University Graduate School of Medicine kn-affil= affil-num=49 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=50 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=51 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=52 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=53 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=54 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=55 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University kn-affil= en-keyword=Metastatic spinal tumors kn-keyword=Metastatic spinal tumors en-keyword=Spine stabilization kn-keyword=Spine stabilization en-keyword=Decompression kn-keyword=Decompression en-keyword=Propensity score matching kn-keyword=Propensity score matching en-keyword=Multicenter prospective study kn-keyword=Multicenter prospective study en-keyword=The epidural spinal cord compression (ESCC) score kn-keyword=The epidural spinal cord compression (ESCC) score END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=20 article-no= start-page=3351 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251017 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tertiary Lymphoid Structures Are Associated with Favorable Clinical Outcomes and Negatively Correlated with Cancer-Associated Fibroblasts in Esophageal Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Esophageal cancer remains a highly aggressive malignant tumor with poor prognosis, despite advances in combination therapies and novel immunotherapies. Tertiary lymphoid structures (TLSs), characterized by densely packed CD20+ B cells in a germinal-center-like structure, have recently been recognized as immune-stimulating components within the tumor microenvironment. In contrast, cancer-associated fibroblasts (CAFs) are stromal cells expressing fibroblast-activating protein (FAP) involved in immunosuppression. Methods: In this retrospective study, 124 clinical samples from patients who underwent radical surgery for esophageal cancer at our institute were analyzed. We investigated whether TLSs could serve as a prognostic factor and examined their association with tumor microenvironment factors. Results: The presence of TLSs was an independent prognostic factor for overall and progression-free survival in multivariate analyses. A high level of TLS formation correlated with better nutritional status, fewer M2 macrophages, and greater plasma cell infiltration. Additionally, little TLS formation was observed in areas with abundant CAFs, and quantitative analyses revealed a significant negative correlation between TLSs and CAFs. Conclusions: TLSs enhance antitumor immunity via macrophages and plasma cells and can be a valuable prognostic indicator in patients undergoing surgery for esophageal cancer. Targeting CAFs may prove to be a promising therapeutic strategy to enhance tumor-immunity-related TLSs. en-copyright= kn-copyright= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraSeitaro en-aut-sei=Nishimura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoHijiri en-aut-sei=Matsumoto en-aut-mei=Hijiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiTatsuya en-aut-sei=Takahashi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkaiMasaaki en-aut-sei=Akai en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=tertiary lymphoid structures (TLSs) kn-keyword=tertiary lymphoid structures (TLSs) en-keyword=cancer-associated fibroblasts (CAFs) kn-keyword=cancer-associated fibroblasts (CAFs) en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=prognosis kn-keyword=prognosis END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=INF2-Related Charcot–Marie–Tooth Disease in a Japanese Cohort: Genetic and Clinical Insights en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: INF2 mutations cause focal segmental glomerulosclerosis (FSGS) and Charcot–Marie–Tooth disease (CMT). Accurate genetic diagnosis is critical, as INF2-related FSGS is typically resistant to immunotherapy yet rarely recurs after transplantation, and its associated neuropathy can mimic treatable immune-mediated disorders such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
Methods: We performed a multicenter study investigating 3329 Japanese patients with inherited peripheral neuropathies/CMT who underwent gene panel sequencing or whole-exome analysis between 2007 and 2024. Clinical data, including electrophysiological assessments, were obtained from the patients' medical records.
Results: We identified six pathogenic INF2 variants in eight patients, all of which were located within the diaphanous inhibitory domain. Structural modeling revealed clustering of variants near the diaphanous autoregulatory domain-binding pocket, which is critical for INF2 autoinhibition. Clinically, all cases were sporadic, with a median age at neurological onset of 9 years. All patients exhibited lower limb weakness, and 6/8 (75%) had sensory disturbances. All patients also developed kidney dysfunction, with 7/8 (88%) progressing to end-stage renal disease at a median age of 15 years. Furthermore, all patients showed demyelinating neuropathy, and 2/8 (25%) received immunotherapy due to suspected immune-mediated neuropathy.
Conclusion: Although INF2 variants are a rare cause of CMT in Japan, they should be considered in pediatric patients with demyelinating neuropathy and early-onset proteinuria, even in the absence of a family history. Blood and urine tests assessing renal dysfunction can provide guidance for appropriate genetic testing. en-copyright= kn-copyright= en-aut-name=YanoChikashi en-aut-sei=Yano en-aut-mei=Chikashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AndoMasahiro en-aut-sei=Ando en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiguchiYujiro en-aut-sei=Higuchi en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YuanJun‐Hui en-aut-sei=Yuan en-aut-mei=Jun‐Hui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimuraAkiko en-aut-sei=Yoshimura en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HobaraTakahiro en-aut-sei=Hobara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagatomoRisa en-aut-sei=Nagatomo en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KojimaFumikazu en-aut-sei=Kojima en-aut-mei=Fumikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiramatsuYu en-aut-sei=Hiramatsu en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NozumaSatoshi en-aut-sei=Nozuma en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraTomonori en-aut-sei=Nakamura en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SakiyamaYusuke en-aut-sei=Sakiyama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KimuraTakashi en-aut-sei=Kimura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiyazakiAyako en-aut-sei=Miyazaki en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KinjoChinatsu en-aut-sei=Kinjo en-aut-mei=Chinatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YokochiKenji en-aut-sei=Yokochi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamanakaNanami en-aut-sei=Yamanaka en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MatsudaNozomu en-aut-sei=Matsuda en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SuichiTomoki en-aut-sei=Suichi en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HanaokaYoshiyuki en-aut-sei=Hanaoka en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KojimaHaruka en-aut-sei=Kojima en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TodoKenichi en-aut-sei=Todo en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TakashimaHiroshi en-aut-sei=Takashima en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=2 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=3 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=4 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=5 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=7 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=8 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=9 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=10 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=11 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=12 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=13 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Neurology, Hyogo Medical University kn-affil= affil-num=16 en-affil=Department of Clinical Genetics, Hyogo Medical University kn-affil= affil-num=17 en-affil=Department of Clinical Genetics, Hyogo Medical University kn-affil= affil-num=18 en-affil=Department of Pediatrics, Toyohashi Municipal Hospital kn-affil= affil-num=19 en-affil=Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Neurology, Fukushima Medical University School of Medicine kn-affil= affil-num=21 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=22 en-affil=Department of Pediatrics, Kurashiki Central Hospital kn-affil= affil-num=23 en-affil=Department of Neurology, Tokyo Women's Medical University kn-affil= affil-num=24 en-affil=Department of Neurology, Tokyo Women's Medical University kn-affil= affil-num=25 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=27 en-affil=Department of Neurology, The University of Tokyo Hospital kn-affil= affil-num=28 en-affil=Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=Charcot-Marie- Tooth disease kn-keyword=Charcot-Marie- Tooth disease en-keyword=focal segmental glomerulosclerosis kn-keyword=focal segmental glomerulosclerosis en-keyword=INF2 kn-keyword=INF2 en-keyword=inherited peripheral neuropathies kn-keyword=inherited peripheral neuropathies en-keyword=neuropathy kn-keyword=neuropathy END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=399 end-page=404 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Epstein-Barr Virus-Associated Early Gastric Carcinoma with Lymphoid Stroma Mimicking a Submucosal Tumor: A Typical Case Diagnosed by Endoscopic Resection and Treated by Local Resection with Sentinel Node Navigation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastric cancer with lymphoid stroma (GCLS) accounts for 1%-7% of gastric cancers; ~80% are Epstein-Barr virus (EBV)-positive. The rate of lymph node metastasis is relatively low, even when an early GCLS has invaded the submucosa. We report an early GCLS with massive submucosal invasion mimicking a submucosal tumor (SMT), diagnosed by endoscopic submucosal resection (ESD) and treated with local resection and sentinel node navigation surgery (SNNS). The patient was a 40-year-old Japanese man. A protruding lesion on the greater curvature of the middle part of his stomach was detected by X-ray, and an endoscopic examination revealed a 2.5-cm protruding tumor covered with a normal mucosa and small ulcers at the apex. ESD was performed for a diagnosis. The pathological diagnosis was lymphoepithelioma-like gastric cancer (GCLS), pT1b(SM2), Ly0, V0, pHM1, pVM1. EBV infection in the cancer cells was confirmed pathologically by EBV-encoded RNA. The local resection was performed using SNNS. The patient has had no recurrence or post-gastrectomy syndrome 4 years postsurgery. EBV-associated early GCLS resembling an SMT is relatively rare, and clinicians need to be aware of this disease. Local resection using SNNS may be a surgical option for GCLS cases with a low rate of lymphatic metastasis. en-copyright= kn-copyright= en-aut-name=IsozakiHiroshi en-aut-sei=Isozaki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoSasau en-aut-sei=Matsumoto en-aut-mei=Sasau kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakamaTakehiro en-aut-sei=Takama en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IsozakiYuka en-aut-sei=Isozaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShigeki en-aut-sei=Murakami en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Oomoto Hospital kn-affil= en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=gastric cancer with lymphoid stroma kn-keyword=gastric cancer with lymphoid stroma en-keyword=lymphoepithelioma-like carcinoma kn-keyword=lymphoepithelioma-like carcinoma en-keyword=Epstein Barr virus kn-keyword=Epstein Barr virus en-keyword=sentinel node navigation surgery kn-keyword=sentinel node navigation surgery END start-ver=1.4 cd-journal=joma no-vol=88 cd-vols= no-issue=9 article-no= start-page=1117 end-page=1125 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240622 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Solid-state cultivation of multiple industrial strains of koji mold on different Thai unpolished rice cultivars: biotransformation of phenolic compounds and their effects on antioxidant activity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colored rice is abundant in polyphenols, and koji molds have potential for biotransformation. This study aimed to produce Thai-colored rice koji to study its polyphenolic biotransformation. Four industrial koji mold strains: Aspergillus oryzae 6001, A. oryzae 6020, A. sojae 7009, and A. luchuensis 8035, were cultivated on unpolished Thai-colored rice (Riceberry and Sangyod), unpolished Thai white rice (RD43), and polished Japanese white rice (Koshihikari). We discovered that koji molds grew on all the rice varieties. Methanol extracts of all rice kojis exhibited an approximately 2-fold or greater increase in total phenolic content and DPPH antioxidant activity compared to those of steamed rice. Moreover, quercetin, quercetin-3-O-glucoside, isorhamnetin-3-O-glucoside, ferulic acid, caffeic acid, protocatechuic acid, vanillic acid, (+)-catechin, and (–)-epicatechin content increased in Riceberry and Sangyod koji samples. Consequently, Aspergillus solid-state cultivation on unpolished Thai-colored rice exhibited higher functionalization than the cultivation of unpolished Thai white rice and polished Japanese white rice. en-copyright= kn-copyright= en-aut-name=JitpakdeeJirayu en-aut-sei=Jitpakdee en-aut-mei=Jirayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamashitaHideyuki en-aut-sei=Yamashita en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakagawaTakuro en-aut-sei=Nakagawa en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NitodaTeruhiko en-aut-sei=Nitoda en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanzakiHiroshi en-aut-sei=Kanzaki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Higuchi Matsunosuke Shoten Co., Ltd. kn-affil= affil-num=3 en-affil=Higuchi Matsunosuke Shoten Co., Ltd. kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=antioxidant activity kn-keyword=antioxidant activity en-keyword=koji mold kn-keyword=koji mold en-keyword=polyphenols kn-keyword=polyphenols en-keyword=solid-state fermentation kn-keyword=solid-state fermentation en-keyword=Thai colored rice kn-keyword=Thai colored rice END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=5 article-no= start-page=650 end-page=661 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development and validation of an algorithm for identifying patients undergoing dialysis from patients with advanced chronic kidney disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Identifying patients on dialysis among those with an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2 remains challenging. To facilitate clinical research in advanced chronic kidney disease (CKD) using electronic health records, we aimed to develop algorithms to identify dialysis patients using laboratory data obtained in routine practice.
Methods We collected clinical data of patients with an eGFR < 15 mL/min/1.73 m2 from six clinical research core hospitals across Japan: four hospitals for the derivation cohort and two for the validation cohort. The candidate factors for the classification models were identified using logistic regression with stepwise backward selection. To ensure transplant patients were not included in the non-dialysis population, we excluded individuals with the disease code Z94.0.
Results We collected data from 1142 patients, with 640 (56%) currently undergoing hemodialysis or peritoneal dialysis (PD), including 426 of 763 patients in the derivation cohort and 214 of 379 patients in the validation cohort. The prescription of PD solutions perfectly identified patients undergoing dialysis. After excluding patients prescribed PD solutions, seven laboratory parameters were included in the algorithm. The areas under the receiver operation characteristic curve were 0.95 and 0.98 and the positive and negative predictive values were 90.9% and 91.4% in the derivation cohort and 96.2% and 94.6% in the validation cohort, respectively. The calibrations were almost linear.
Conclusions We identified patients on dialysis among those with an eGFR < 15 ml/min/1.73 m2. This study paves the way for database research in nephrology, especially for patients with non-dialysis-dependent advanced CKD. en-copyright= kn-copyright= en-aut-name=ImaizumiTakahiro en-aut-sei=Imaizumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokotaTakashi en-aut-sei=Yokota en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FunakoshiKouta en-aut-sei=Funakoshi en-aut-mei=Kouta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasudaKazushi en-aut-sei=Yasuda en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HattoriAkiko en-aut-sei=Hattori en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorohashiAkemi en-aut-sei=Morohashi en-aut-mei=Akemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KusakabeTatsumi en-aut-sei=Kusakabe en-aut-mei=Tatsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShojimaMasumi en-aut-sei=Shojima en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagamineSayoko en-aut-sei=Nagamine en-aut-mei=Sayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanoToshiaki en-aut-sei=Nakano en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HuangYong en-aut-sei=Huang en-aut-mei=Yong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhtaMiki en-aut-sei=Ohta en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagashimaSatomi en-aut-sei=Nagashima en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=InoueRyusuke en-aut-sei=Inoue en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakamuraNaoki en-aut-sei=Nakamura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OtaHideki en-aut-sei=Ota en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MaruyamaTatsuya en-aut-sei=Maruyama en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=GobaraHideo en-aut-sei=Gobara en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=EndohAkira en-aut-sei=Endoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AndoMasahiko en-aut-sei=Ando en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShiratoriYoshimune en-aut-sei=Shiratori en-aut-mei=Yoshimune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MaruyamaShoichi en-aut-sei=Maruyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital kn-affil= affil-num=3 en-affil=Kyusyu University Hospital kn-affil= affil-num=4 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Advanced Medicine, Nagoya University Hospital kn-affil= affil-num=7 en-affil=Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital kn-affil= affil-num=8 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=11 en-affil=Division of Medical Informatics, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Comprehensive Therapy for Chronic Kidney Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Clinical Research Promotion Center, The University of Tokyo Hospital kn-affil= affil-num=14 en-affil=Department of Healthcare Information Management, The University of Tokyo Hospital kn-affil= affil-num=15 en-affil=Medical Information Technology Center, Tohoku University Hospital kn-affil= affil-num=16 en-affil=Medical Information Technology Center, Tohoku University Hospital kn-affil= affil-num=17 en-affil=Medical Information Technology Center, Tohoku University Hospital kn-affil= affil-num=18 en-affil=Clinical Research Promotion Center, The University of Tokyo Hospital kn-affil= affil-num=19 en-affil=Division of Medical Informatics, Okayama University Hospital kn-affil= affil-num=20 en-affil=Department of Medical Informatics, Hokkaido University Hospital kn-affil= affil-num=21 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Medical IT Center, Nagoya University Hospital kn-affil= affil-num=23 en-affil=Department of Nephrology, Nagoya University Graduate School of Medicine kn-affil= en-keyword=Chronic kidney disease kn-keyword=Chronic kidney disease en-keyword=Algorithm kn-keyword=Algorithm en-keyword=Classification kn-keyword=Classification en-keyword=Dialysis kn-keyword=Dialysis END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=1 article-no= start-page=e12658 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Can online interactions reduce loneliness in young adults during university closures in Japan? The directed acyclic graphs approach en-subtitle= kn-subtitle= en-abstract= kn-abstract=As a countermeasure to the increased loneliness induced by the COVID-19 pandemic-related university closures, universities provided students with online interaction opportunities. However, whether these opportunities contributed to reducing loneliness during the university closures remains unclear, as previous studies have produced contradictory findings. We conducted a nationwide cross-sectional survey. Data were collected on demographics, social environment, social support, interactions, health and loneliness from 4949 students from 60 universities across Japan. We used psychological network and Directed Acyclic Graphs (DAGs) to examine the effect of online interactions on loneliness during university closures during COVID-19. The results showed that the frequency of online interactions with friends did not exert a significant influence on loneliness during university closures. A comparative examination of the DAGs further illuminated that the social environment exhibited fewer pathways for interpersonal interactions and social support during these closure periods. The psychosocial pathways influencing young adults' loneliness show variations contingent on the university's closure status. Notably, the impact of heightened online interactions with friends on loneliness appears to be less pronounced among young adults in the context of university closure. en-copyright= kn-copyright= en-aut-name=KambaraKohei en-aut-sei=Kambara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToyaAkihiro en-aut-sei=Toya en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LeeSumin en-aut-sei=Lee en-aut-mei=Sumin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimizuHaruka en-aut-sei=Shimizu en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbeKazuaki en-aut-sei=Abe en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShigematsuJun en-aut-sei=Shigematsu en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangQingyuan en-aut-sei=Zhang en-aut-mei=Qingyuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AbeNatsuki en-aut-sei=Abe en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HayaseRyo en-aut-sei=Hayase en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AbeNobuhito en-aut-sei=Abe en-aut-mei=Nobuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakaiRyusuke en-aut-sei=Nakai en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AokiShuntaro en-aut-sei=Aoki en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AsanoKohei en-aut-sei=Asano en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AsanoRyosuke en-aut-sei=Asano en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujimuraMakoto en-aut-sei=Fujimura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FukuiKen’ichiro en-aut-sei=Fukui en-aut-mei=Ken’ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukumotoYoshihiro en-aut-sei=Fukumoto en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FurutaniKaichiro en-aut-sei=Furutani en-aut-mei=Kaichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HasegawaKoji en-aut-sei=Hasegawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HashimotoHirofumi en-aut-sei=Hashimoto en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HashimotoMikoto en-aut-sei=Hashimoto en-aut-mei=Mikoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HosogoshiHiroki en-aut-sei=Hosogoshi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=IkedaHiroshi en-aut-sei=Ikeda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=IshiokaToshiyuki en-aut-sei=Ishioka en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ItoChiharu en-aut-sei=Ito en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IwanoSuguru en-aut-sei=Iwano en-aut-mei=Suguru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KamadaMasafumi en-aut-sei=Kamada en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KanaiYoshihiro en-aut-sei=Kanai en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KaritaTomonori en-aut-sei=Karita en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=KasagiYu en-aut-sei=Kasagi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=KashimaEmiko S. en-aut-sei=Kashima en-aut-mei=Emiko S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=KatoJuri en-aut-sei=Kato en-aut-mei=Juri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawachiYousuke en-aut-sei=Kawachi en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KawaharaJun‐ichiro en-aut-sei=Kawahara en-aut-mei=Jun‐ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=KimuraMasanori en-aut-sei=Kimura en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=KiraYugo en-aut-sei=Kira en-aut-mei=Yugo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=Kiyonaga (Sakoda)Yuko en-aut-sei=Kiyonaga (Sakoda) en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KohguchiHiroshi en-aut-sei=Kohguchi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=KomiyaAsuka en-aut-sei=Komiya en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=MasuiKeita en-aut-sei=Masui en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=MidorikawaAkira en-aut-sei=Midorikawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=MifuneNobuhiro en-aut-sei=Mifune en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=MizukoshiAkimine en-aut-sei=Mizukoshi en-aut-mei=Akimine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=NawataKengo en-aut-sei=Nawata en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=NishimuraTakashi en-aut-sei=Nishimura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=NogiwaDaisuke en-aut-sei=Nogiwa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=OgawaKenji en-aut-sei=Ogawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=OkadaJunko en-aut-sei=Okada en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=OkamotoAki en-aut-sei=Okamoto en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=OkamotoReiko en-aut-sei=Okamoto en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=SasakiKyoko en-aut-sei=Sasaki en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=SatoKosuke en-aut-sei=Sato en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=ShimizuHiroshi en-aut-sei=Shimizu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=SugimuraAtsushi en-aut-sei=Sugimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=SugitaniYoko en-aut-sei=Sugitani en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=SugiuraHitomi en-aut-sei=Sugiura en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=SumiokaKyoko en-aut-sei=Sumioka en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=SunaguchiBumpei en-aut-sei=Sunaguchi en-aut-mei=Bumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=TakebeMasataka en-aut-sei=Takebe en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=TanabeHiroki C. en-aut-sei=Tanabe en-aut-mei=Hiroki C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=TanakaAyumi en-aut-sei=Tanaka en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= en-aut-name=TanakaMasanori en-aut-sei=Tanaka en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=62 ORCID= en-aut-name=TaniguchiJunichi en-aut-sei=Taniguchi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=63 ORCID= en-aut-name=TokunagaNamiji en-aut-sei=Tokunaga en-aut-mei=Namiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=64 ORCID= en-aut-name=TomitaRyozo en-aut-sei=Tomita en-aut-mei=Ryozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=65 ORCID= en-aut-name=UedaYumiko en-aut-sei=Ueda en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=66 ORCID= en-aut-name=YamashitaTomomi en-aut-sei=Yamashita en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=67 ORCID= en-aut-name=YamauraKazuho en-aut-sei=Yamaura en-aut-mei=Kazuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=68 ORCID= en-aut-name=YogoMasao en-aut-sei=Yogo en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=69 ORCID= en-aut-name=YokotaniKenji en-aut-sei=Yokotani en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=70 ORCID= en-aut-name=YoshidaAyano en-aut-sei=Yoshida en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=71 ORCID= en-aut-name=YoshidaHiroaki en-aut-sei=Yoshida en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=72 ORCID= en-aut-name=YoshiharaKatsue en-aut-sei=Yoshihara en-aut-mei=Katsue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=73 ORCID= en-aut-name=YoshikawaAyumi en-aut-sei=Yoshikawa en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=74 ORCID= en-aut-name=YanagisawaKuniaki en-aut-sei=Yanagisawa en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=75 ORCID= en-aut-name=NakashimaKen'ichiro en-aut-sei=Nakashima en-aut-mei=Ken'ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=76 ORCID= affil-num=1 en-affil=Doshisha University kn-affil= affil-num=2 en-affil=Hiroshima University kn-affil= affil-num=3 en-affil=Hiroshima University kn-affil= affil-num=4 en-affil=Nishikyushu Univ. Junior College kn-affil= affil-num=5 en-affil=Hiroshima University kn-affil= affil-num=6 en-affil=Toyama University kn-affil= affil-num=7 en-affil=Hiroshima University kn-affil= affil-num=8 en-affil=Hiroshima Bunkyo University kn-affil= affil-num=9 en-affil=Chubu University kn-affil= affil-num=10 en-affil=Kyoto University kn-affil= affil-num=11 en-affil=Kyoto University kn-affil= affil-num=12 en-affil=Fukushima Medical University kn-affil= affil-num=13 en-affil=Kyoto University kn-affil= affil-num=14 en-affil=Kurume University kn-affil= affil-num=15 en-affil=Fukuoka Jo Gakuin University kn-affil= affil-num=16 en-affil=Kwassui Women's University kn-affil= affil-num=17 en-affil=Kansai Medical University kn-affil= affil-num=18 en-affil=Kansai University kn-affil= affil-num=19 en-affil=Komazawa University kn-affil= affil-num=20 en-affil=Osaka Metropolitan University kn-affil= affil-num=21 en-affil=Chukyo Gakuin University kn-affil= affil-num=22 en-affil=Kansai University kn-affil= affil-num=23 en-affil=Kyushu University kn-affil= affil-num=24 en-affil=Kobe University kn-affil= affil-num=25 en-affil=University of Human Environments kn-affil= affil-num=26 en-affil=Fukushima Medical University kn-affil= affil-num=27 en-affil=Shujitsu Junior College kn-affil= affil-num=28 en-affil=Tohoku Gakuin University kn-affil= affil-num=29 en-affil=Ehime University kn-affil= affil-num=30 en-affil=Rissho University kn-affil= affil-num=31 en-affil=La Trobe University kn-affil= affil-num=32 en-affil=Kanazawa Institute of Technology kn-affil= affil-num=33 en-affil=Tohoku University kn-affil= affil-num=34 en-affil=Hokkaido University kn-affil= affil-num=35 en-affil=Graduate School of Business Administration, Kobe University kn-affil= affil-num=36 en-affil=Kurume University kn-affil= affil-num=37 en-affil=Kyushu Kyoritsu University kn-affil= affil-num=38 en-affil=Ryutsu Keizai University kn-affil= affil-num=39 en-affil=Hiroshima University kn-affil= affil-num=40 en-affil=Otemon Gakuin University kn-affil= affil-num=41 en-affil=Chuo University kn-affil= affil-num=42 en-affil=Kochi University of Technology kn-affil= affil-num=43 en-affil=Asahi University kn-affil= affil-num=44 en-affil=Fukuoka University kn-affil= affil-num=45 en-affil=Hiroshima International University kn-affil= affil-num=46 en-affil=Seikei University kn-affil= affil-num=47 en-affil=Hokkaido University kn-affil= affil-num=48 en-affil=Prefectural University of Hiroshima kn-affil= affil-num=49 en-affil=Okayama University kn-affil= affil-num=50 en-affil=Osaka University kn-affil= affil-num=51 en-affil=Kanagawa University of Human Services kn-affil= affil-num=52 en-affil=Kurume University kn-affil= affil-num=53 en-affil=Kwansei Gakuin University kn-affil= affil-num=54 en-affil=Tokai University kn-affil= affil-num=55 en-affil=Sophia University kn-affil= affil-num=56 en-affil=Kindai University kn-affil= affil-num=57 en-affil=Okayama University kn-affil= affil-num=58 en-affil=Graduate School of Business Administration, Kobe University kn-affil= affil-num=59 en-affil=Otsuma Women's University kn-affil= affil-num=60 en-affil=Nagoya University kn-affil= affil-num=61 en-affil=Doshisha University kn-affil= affil-num=62 en-affil=Hokkai‐Gakuen University kn-affil= affil-num=63 en-affil=Tezukayama University kn-affil= affil-num=64 en-affil=Ehime Prefectural University of Health Sciences kn-affil= affil-num=65 en-affil=Musashino University kn-affil= affil-num=66 en-affil=Asahi University kn-affil= affil-num=67 en-affil=Jumonji University kn-affil= affil-num=68 en-affil=Ritsumeikan University kn-affil= affil-num=69 en-affil=Doshisha University kn-affil= affil-num=70 en-affil=Tokushima University kn-affil= affil-num=71 en-affil=Tohoku Fukushi University kn-affil= affil-num=72 en-affil=Shinshu University kn-affil= affil-num=73 en-affil=Fukuoka Institute of Technology Junior College kn-affil= affil-num=74 en-affil=Osaka Dental University Faculty of Nursing kn-affil= affil-num=75 en-affil=Kobe University kn-affil= affil-num=76 en-affil=Hiroshima University kn-affil= en-keyword=directed acyclic graphs kn-keyword=directed acyclic graphs en-keyword=loneliness kn-keyword=loneliness en-keyword=online interactions kn-keyword=online interactions en-keyword=psychological network kn-keyword=psychological network en-keyword=university closures kn-keyword=university closures en-keyword=university students kn-keyword=university students END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=519 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250926 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Specific induction of right ventricular-like cardiomyocytes from human pluripotent stem cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Applications employing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) require well-characterized, chamber-specific hPSC-CMs. Distinct first heart field (FHF) and second heart field (SHF) cardiac progenitor populations give rise to the left ventricular (LV) and right ventricular (RV) cardiomyocytes, respectively. This developmental difference in cardiomyocyte origin suggests that chamber-specific cardiomyocytes have unique characteristics. Therefore, efficient strategies to differentiate human pluripotent stem cells (hPSCs) specifically to LV-like or RV-like cardiomyocytes are needed and it is still unknown whether there is a phenotypic difference between LV-like cardiomyocytes and RV-like cardiomyocytes derived from hPSCs.
Methods An established hPSC cardiac differentiation protocol employing sequential GSK3β inhibition followed by Wnt inhibition (GiWi) was modified by addition of insulin or BMP antagonists during mesoderm formation. Cardiac progenitor populations were evaluated for FHF and SHF markers, and differentiated hPSC-CMs were characterized for chamber-specific markers.
Results The GiWi protocol produced mainly FHF-like progenitor cells that gave rise to LV-like cardiomyocytes. Inhibition of endogenous BMP signaling during mesoderm induction using insulin or BMP antagonists reduced expression of FHF markers and increased expression of SHF markers in cardiac progenitor cells. hPSC-CMs arising from the SHF-like progenitor cells showed an RV-like gene expression pattern and exhibited phenotypic differences in spontaneous contraction rate, Ca2+ transients, and cell size compared to control LV-like cardiomyocytes.
Conclusion This study establishes methodology to generate RV-like hPSC-CMs to support the development of disease modeling research using chamber-specific hPSC-CMs. en-copyright= kn-copyright= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatanosakaYuki en-aut-sei=Katanosaka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IidaToshihiro en-aut-sei=Iida en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KusumotoDai en-aut-sei=Kusumoto en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoRyushi en-aut-sei=Sato en-aut-mei=Ryushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AdachiRiki en-aut-sei=Adachi en-aut-mei=Riki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuSatoshi en-aut-sei=Shimizu en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurokawaJunko en-aut-sei=Kurokawa en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishidaMikako en-aut-sei=Nishida en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ZhangJianhua en-aut-sei=Zhang en-aut-mei=Jianhua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KampTimothy J. en-aut-sei=Kamp en-aut-mei=Timothy J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Biomedical Informatics and Molecular Biology, The Sakaguchi Laboratory, Keio University School of Medicine kn-affil= affil-num=6 en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka kn-affil= affil-num=7 en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka kn-affil= affil-num=8 en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka kn-affil= affil-num=9 en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Medicine, University of Wisconsin School of Medicine and Public Health kn-affil= affil-num=18 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Medicine, University of Wisconsin School of Medicine and Public Health kn-affil= affil-num=20 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Human pluripotent stem cell-derived cardiomyocytes kn-keyword=Human pluripotent stem cell-derived cardiomyocytes en-keyword=Anterior second heart field kn-keyword=Anterior second heart field en-keyword=Right ventricle kn-keyword=Right ventricle en-keyword=Bone morphogenetic protein kn-keyword=Bone morphogenetic protein END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=21 article-no= start-page=11479 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dennd2c Negatively Controls Multinucleation and Differentiation in Osteoclasts by Regulating Actin Polymerization and Protrusion Formation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteoclasts are bone-resorbing multinucleated giant cells formed by the fusion of monocyte/macrophage lineages. Various small GTPases are involved in the multinucleation and differentiation of osteoclasts. However, the roles of small GTPases regulatory molecules in osteoclast differentiation remain unclear. In the present study, we examined the role of Dennd2c, a putative guanine nucleotide exchange factor for Rab GTPases, in osteoclast differentiation. Knockdown of Dennd2c promoted osteoclast differentiation, resorption, and expression of osteoclast markers. Morphologically, Dennd2c knockdown induced the formation of larger osteoclasts with several protrusions. In contrast, overexpression of Dennd2c inhibited the multinucleation and differentiation of osteoclasts, bone resorption, and the expression of osteoclast markers. Dennd2c-overexpressing macrophages exhibited spindle-shaped mononuclear cells and long thin protrusions. Treatment of Dennd2c-overexpressing cells with the Cdc42 inhibitor ML-141 or the Rac1 inhibitor 6-thio-GTP prevented protrusion formation. Moreover, treatment of Dennd2c-overexpressing cells with the actin polymerization inhibitor latrunculin B restored multinucleated and TRAP-positive osteoclast formation. These results indicate that Dennd2c negatively regulates osteoclast differentiation and multinucleation by modulating protrusion formation in macrophages. en-copyright= kn-copyright= en-aut-name=KoyanagiYu en-aut-sei=Koyanagi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakaiEiko en-aut-sei=Sakai en-aut-mei=Eiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamaguchiYu en-aut-sei=Yamaguchi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FarhanaFatima en-aut-sei=Farhana en-aut-mei=Fatima kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TairaYohsuke en-aut-sei=Taira en-aut-mei=Yohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurataHiroshi en-aut-sei=Murata en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsukubaTakayuki en-aut-sei=Tsukuba en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=4 en-affil=Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=5 en-affil=Division of Cariology and Restorative Dentistry, Department of Prosthetic Dentistry, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=6 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Division of Cariology and Restorative Dentistry, Department of Prosthetic Dentistry, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=8 en-affil=Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= en-keyword=osteoclast kn-keyword=osteoclast en-keyword=actin polymerization kn-keyword=actin polymerization en-keyword=protrusion formation kn-keyword=protrusion formation en-keyword=Dennd2c kn-keyword=Dennd2c END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=e70004 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oregon Wolfe barley genetic stocks – Research and teaching tools for next generation scientists en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Oregon Wolfe Barley (OWB) mapping population (Reg. no. MP-4, NSL 554937 MAP) is a resource for genetics research and instruction. The OWBs are a set of doubled haploid barley (Hordeum vulgare L.) lines developed at Oregon State University from the F1 of a cross between Dr. Robert Wolfe's dominant and recessive marker stocks. Exhibiting a high level of genetic and phenotypic diversity, the OWBs are used throughout the world as a research tool for barley genetics. To date, these endeavors have led to 56 peer-reviewed publications, as well as three reports in the Barley Genetics Newsletter. At the same time, the OWBs are widely used as an instructor resource at the K–12, undergraduate, graduate, and professional levels. They are currently used at universities and/or institutes in German, Italy, Norway, Spain, and the United States and are currently being developed further for educational use in other countries. Genotype and phenotype data, lesson plans, and seed availability information are available herein and online. en-copyright= kn-copyright= en-aut-name=KrauseMargaret R. en-aut-sei=Krause en-aut-mei=Margaret R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ArbelaezJuan David en-aut-sei=Arbelaez en-aut-mei=Juan David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsdalÅsmund en-aut-sei=Asdal en-aut-mei=Åsmund kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BelkodjaRamzi en-aut-sei=Belkodja en-aut-mei=Ramzi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BouryNancy en-aut-sei=Boury en-aut-mei=Nancy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BlakeVictoria C. en-aut-sei=Blake en-aut-mei=Victoria C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BrownPatrick J. en-aut-sei=Brown en-aut-mei=Patrick J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CasasAna en-aut-sei=Casas en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CistuéLuis en-aut-sei=Cistué en-aut-mei=Luis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Farré‐MartínezAlba en-aut-sei=Farré‐Martínez en-aut-mei=Alba kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FiskScott en-aut-sei=Fisk en-aut-mei=Scott kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FuerstGregory S. en-aut-sei=Fuerst en-aut-mei=Gregory S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GiménezEstela en-aut-sei=Giménez en-aut-mei=Estela kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Guijarro‐RealCarla en-aut-sei=Guijarro‐Real en-aut-mei=Carla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=GuthrieKaty en-aut-sei=Guthrie en-aut-mei=Katy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HalsteadMargaret en-aut-sei=Halstead en-aut-mei=Margaret kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HelgersonLaura en-aut-sei=Helgerson en-aut-mei=Laura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IgartuaErnesto en-aut-sei=Igartua en-aut-mei=Ernesto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=LillemoMorten en-aut-sei=Lillemo en-aut-mei=Morten kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=Martínez‐GarcíaMarina en-aut-sei=Martínez‐García en-aut-mei=Marina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=Martínez‐SubiràMariona en-aut-sei=Martínez‐Subirà en-aut-mei=Mariona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=McCouchSusan en-aut-sei=McCouch en-aut-mei=Susan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=McGheeLaurie en-aut-sei=McGhee en-aut-mei=Laurie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NickolsTravis en-aut-sei=Nickols en-aut-mei=Travis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=PetersNick en-aut-sei=Peters en-aut-mei=Nick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=PorterRaymond en-aut-sei=Porter en-aut-mei=Raymond kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=RomagosaIgnacio en-aut-sei=Romagosa en-aut-mei=Ignacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=RuudAnja Karine en-aut-sei=Ruud en-aut-mei=Anja Karine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=SalviSilvio en-aut-sei=Salvi en-aut-mei=Silvio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=SangiorgiGiuseppe en-aut-sei=Sangiorgi en-aut-mei=Giuseppe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=SchüllerRebekka en-aut-sei=Schüller en-aut-mei=Rebekka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=SenTaner Z. en-aut-sei=Sen en-aut-mei=Taner Z. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=SorianoJosé Miguel en-aut-sei=Soriano en-aut-mei=José Miguel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=StuparRobert M. en-aut-sei=Stupar en-aut-mei=Robert M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=TingTo‐Chia en-aut-sei=Ting en-aut-mei=To‐Chia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=ViningKelly en-aut-sei=Vining en-aut-mei=Kelly kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=von KorffMaria en-aut-sei=von Korff en-aut-mei=Maria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=WallaAgatha en-aut-sei=Walla en-aut-mei=Agatha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=WangDiane R. en-aut-sei=Wang en-aut-mei=Diane R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=WaughRobbie en-aut-sei=Waugh en-aut-mei=Robbie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=WiseRoger P. en-aut-sei=Wise en-aut-mei=Roger P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=WolfeRobert en-aut-sei=Wolfe en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=YaoEric en-aut-sei=Yao en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=HayesPatrick M. en-aut-sei=Hayes en-aut-mei=Patrick M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= affil-num=1 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=2 en-affil=Department of Crop Sciences, University of Illinois at Urbana-Champaign kn-affil= affil-num=3 en-affil=Nordic Genetic Resource Centre kn-affil= affil-num=4 en-affil=CIHEAM-Zaragoza kn-affil= affil-num=5 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=6 en-affil=Department of Plant Sciences and Plant Pathology, Montana State University kn-affil= affil-num=7 en-affil=Department of Plant Sciences, University of California-Davis kn-affil= affil-num=8 en-affil=Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC kn-affil= affil-num=9 en-affil=Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC kn-affil= affil-num=10 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=11 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=12 en-affil=U.S. Department of Agriculture-Agricultural Research Service, Corn Insects and Crop Genetics Research Unit, Iowa State University kn-affil= affil-num=13 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid kn-affil= affil-num=14 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid kn-affil= affil-num=15 en-affil=Department of Agronomy and Plant Genetics, University of Minnesota kn-affil= affil-num=16 en-affil=Aardevo North America kn-affil= affil-num=17 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=18 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=19 en-affil=Departamento de Genética y Producción Vegetal, Estación Experimental Aula Dei–CSIC kn-affil= affil-num=20 en-affil=Department of Plant Sciences, Norwegian University of Life Sciences kn-affil= affil-num=21 en-affil=Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid kn-affil= affil-num=22 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=23 en-affil=Plant Breeding and Genetics Section, School of Integrative Plant Science, Cornell University kn-affil= affil-num=24 en-affil=Colfax-Mingo Community High School kn-affil= affil-num=25 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=26 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=27 en-affil=Haupert Institute for Agricultural Studies, Huntington University kn-affil= affil-num=28 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=29 en-affil=Department of Plant Sciences, Norwegian University of Life Sciences kn-affil= affil-num=30 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=31 en-affil=Department of Agricultural and Food Sciences, University of Bologna kn-affil= affil-num=32 en-affil=Department of Agricultural and Food Sciences, University of Bologna kn-affil= affil-num=33 en-affil=Department of Crop Sciences, University of Illinois at Urbana-Champaign kn-affil= affil-num=34 en-affil=Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service kn-affil= affil-num=35 en-affil=AGROTECNIO-CERCA Center, Universidad de Lleida kn-affil= affil-num=36 en-affil=Department of Agronomy and Plant Genetics, University of Minnesota kn-affil= affil-num=37 en-affil=Agronomy Department, Purdue University kn-affil= affil-num=38 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= affil-num=39 en-affil=Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf kn-affil= affil-num=40 en-affil=Institute of Plant Genetics, Heinrich-Heine-Universität Düsseldorf kn-affil= affil-num=41 en-affil=Agronomy Department, Purdue University kn-affil= affil-num=42 en-affil=Division of Plant Sciences, School of Life Sciences, University of Dundee kn-affil= affil-num=43 en-affil=Department of Plant Pathology, Entomology, and Microbiology, Iowa State University kn-affil= affil-num=44 en-affil=Agriculture and Agri-Food Canada kn-affil= affil-num=45 en-affil=Crop Improvement and Genetics Research Unit, U.S. Department of Agriculture-Agricultural Research Service kn-affil= affil-num=46 en-affil=Department of Crop and Soil Science, Oregon State University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=1869 cd-vols= no-issue=12 article-no= start-page=130860 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol–disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in Txn-F54L mutant rats; however, the details of why the Txn mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the Txn-F54L rats. en-copyright= kn-copyright= en-aut-name=BabaTakumi en-aut-sei=Baba en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UenoGo en-aut-sei=Ueno en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OheChika en-aut-sei=Ohe en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SajiShuku en-aut-sei=Saji en-aut-mei=Shuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoSachiko en-aut-sei=Yamamoto en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoMasaki en-aut-sei=Yamamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagawaHiroshi en-aut-sei=Nakagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkazakiNobuo en-aut-sei=Okazaki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Kawasaki-OhmoriIori en-aut-sei=Kawasaki-Ohmori en-aut-mei=Iori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakeshitaKohei en-aut-sei=Takeshita en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=2 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=3 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=4 en-affil=Structural Biology Division, Japan Synchrotron Radiation Research Institute kn-affil= affil-num=5 en-affil=Structural Biology Division, Japan Synchrotron Radiation Research Institute kn-affil= affil-num=6 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=7 en-affil=Materials Sciences Research Center, Japan Atomic Energy Agency kn-affil= affil-num=8 en-affil=Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society (CROSS) kn-affil= affil-num=9 en-affil=Department of Molecular Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University kn-affil= affil-num=11 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= en-keyword=Txn kn-keyword=Txn en-keyword=Thioredoxin kn-keyword=Thioredoxin en-keyword=Protein instability kn-keyword=Protein instability en-keyword=Thermosensitivity kn-keyword=Thermosensitivity en-keyword=Crystal structure kn-keyword=Crystal structure en-keyword=Molecular dynamics simulation kn-keyword=Molecular dynamics simulation END start-ver=1.4 cd-journal=joma no-vol=400 cd-vols= no-issue= article-no= start-page=51 end-page=71 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lithium- and oxygen-isotope compositions of a Si-rich nebular reservoir determined from chondrule constituents in the Sahara 97103 EH3 chondrite en-subtitle= kn-subtitle= en-abstract= kn-abstract=Here we report the in situ ion-microprobe analyses of the Li- and O-isotope compositions of enstatite, FeO-rich pyroxene, olivine, glass, and cristobalite grains from six chondrule-related objects from the Sahara 97103 EH3 chondrite. The O-isotope composition of the enstatite grains scattered around the intersection between the terrestrial fractionation and primitive chondrule minerals lines. Whereas, that of olivine varied along the primitive chondrule minerals line. Based on the mineralogy, we found cristobalite formed as a result of Si saturation, instead of the reduction of FeO-rich silicates, consistent with Si-enrichment of whole rock enstatite chondrites. Based on the mineralogy and O-isotope compositions, we infer that olivines in some chondrules are relict grains. In chondrules that contained olivine, no abundant niningerite [(Mg,Fe,Mn)S] was observed. Thus, enstatite formation can be explained by the interaction of an olivine precursor with additional SiO2 (Mg2SiO4 + SiO2 → Mg2Si2O6), instead of sulfidation (Mg2SiO4 + S → 1/2 Mg2Si2O6 + MgS + 1/2 O2). Using the equation Mg2SiO4 + SiO2 → Mg2Si2O6 and the O-isotope compositions of enstatite and olivine, the O-isotope composition of the additional SiO2 was estimated. Based on the O-isotope composition, we infer that there could be a Si-rich gas with an elevated Δ17O value similar to, or greater than the second trend line (Δ17O = 0.9 ‰) suggested by Weisberg et al. (2021), during chondrule formation. The variation in the Li-isotope compositions of enstatite and olivine grains from EH3 chondrules is smaller than that for the same phases from CV3 chondrules. The variation in the Li-isotope compositions of the enstatite and olivine grains from EH3 chondrules is also smaller than that of their O-isotope compositions. During the recycling of enstatite-chondrite chondrules, both Li- and O-isotope compositions were homogenized. Although enstatite is the major carrier of Li in EH3 chondrules, the Li-isotope composition (δ7Li) of enstatite is lower than that of whole rock EH3 chondrites, suggesting the existence of a phase with higher δ7Li. Meanwhile, the Li-isotope composition and concentration (δ7Li, [Li]) of enstatite is higher than that of olivine. The Li-isotope composition of the Si-rich gas was estimated to be δ7Li = 1 ‰, using a similar mass-balance calculation as applied for the O-isotope composition. The Li-isotope composition of the Si-rich gas from the enstatite-chondrite-chondrule forming-region, is consistent with that of whole rock EH3 chondrites, and differs significantly from that of the Si-rich gas from the carbonaceous-chondrite-chondrule forming-region (δ7Li = −11 ‰) determined by a previous study. We speculate that the Si-rich gas in the carbonaceous-chondrite-chondrule forming-region maintained the Li-isotope heterogeneity inherited from light lithium synthesized by galactic cosmic-ray spallation in the interstellar medium. en-copyright= kn-copyright= en-aut-name=Douglas-SongTorii en-aut-sei=Douglas-Song en-aut-mei=Torii kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaTsutomu en-aut-sei=Ota en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamanakaMasahiro en-aut-sei=Yamanaka en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaRyoji en-aut-sei=Tanaka en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PotiszilChristian en-aut-sei=Potiszil en-aut-mei=Christian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KunihiroTak en-aut-sei=Kunihiro en-aut-mei=Tak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University kn-affil= affil-num=5 en-affil=The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University kn-affil= affil-num=6 en-affil=The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University kn-affil= affil-num=7 en-affil=The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University kn-affil= en-keyword=Lithium kn-keyword=Lithium en-keyword=Oxygen kn-keyword=Oxygen en-keyword=Trace elements kn-keyword=Trace elements en-keyword=Chondrule kn-keyword=Chondrule en-keyword=Enstatite chondrite kn-keyword=Enstatite chondrite en-keyword=SIMS kn-keyword=SIMS en-keyword=Sulfidation kn-keyword=Sulfidation en-keyword=Silicification kn-keyword=Silicification END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=305 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250818 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Precise stratification of prognosis in pancreatic ductal adenocarcinoma patients based on pre- and postoperative genomic information en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate among all cancers; hence, multidisciplinary treatment is essential for patients with PDAC. Although the resectability status, tumour marker, KRAS circulating tumour DNA (mutKRAS-ctDNA) mutations, and GATA binding 6 (GATA6) expression status are promising prognostic biomarkers, their effective integration before and after surgery remains unclear.
Methods In this retrospective cohort study, patients with PDAC who had undergone radical resection were enrolled, and pre- and postoperative independent factors associated with poor prognosis were identified using Cox hazard modelling. Risk stratification systems were developed using the identified prognostic factors and investigated for the ability to predict prognosis.
Results A total of 91 patients with PDAC were included (median follow-up duration, 28 months). Borderline resectable or locally advanced cancer at diagnosis, elevated carbohydrate antigen 19–9 (CA19-9) level, and mutKRAS-ctDNA-positive status were identified as independent preoperative factors associated with poor prognosis. The postoperative factors significantly associated with shorter overall survival were low GATA6 expression, elevated CA19-9 level, and mutKRAS-ctDNA-positive status. Finally, the preoperative and postoperative risk scoring systems developed using Cox modelling hazard ratio values could significantly stratify prognosis after curative resection for PDAC.
Conclusion A risk stratification system based on liquid biopsy, specialised for each phase (pre- and post-surgery), has been proven to be a useful, simple, and practical prognostic prediction clinical tool to determine the optimal multidisciplinary treatment protocol for PDAC. en-copyright= kn-copyright= en-aut-name=MiyamotoKokichi en-aut-sei=Miyamoto en-aut-mei=Kokichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriwakeKazuya en-aut-sei=Moriwake en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KayanoMasashi en-aut-sei=Kayano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NishiyamaTakeyoshi en-aut-sei=Nishiyama en-aut-mei=Takeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MoritaMizuki en-aut-sei=Morita en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=21 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Pancreatic ductal adenocarcinoma kn-keyword=Pancreatic ductal adenocarcinoma en-keyword=Risk stratification kn-keyword=Risk stratification en-keyword=Prognosis kn-keyword=Prognosis en-keyword=Tumour marker kn-keyword=Tumour marker en-keyword=KRAS kn-keyword=KRAS END start-ver=1.4 cd-journal=joma no-vol=156 cd-vols= no-issue=2 article-no= start-page=473 end-page=479.e1 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dried blood spot proteome identifies subclinical interferon signature in neonates with type I interferonopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Type I interferonopathy is characterized by aberrant upregulation of type I interferon signaling. The mRNA interferon signature is a useful marker for activation of the interferon pathway and for diagnosis of type I interferonopathy; however, early diagnosis is challenging.
Objective: This study sought to identify the proteomic interferon signature in dried blood spot (DBS) samples. The aim was to evaluate the usefulness of the interferon signature for neonatal screening and to gain insight into presymptomatic state of neonates with inborn errors of immunity (IEIs).
Methods: DBS samples from healthy newborns/adults, patients with type I interferonopathy or other IEIs as well as from neonates with viral infections, including some samples obtained during the presymptomatic neonatal period, were examined by nontargeted proteome analyses. Expression of interferon-stimulated genes (ISGs) was evaluated and a DBS-interferon signature was defined. Differential expression/pathway analysis was also performed.
Results: The ISG products IFIT5, ISG15, and OAS2 were detected. Expression of IFIT5 and ISG15 was upregulated significantly in individuals with type I interferonopathy. We defined the sum of the z scores for these as the DBS-interferon signature, and found that patients with IEIs other than type I interferonopathy, such as chronic granulomatous disease (CGD), also showed significant elevation. Additionally, neonatal samples of type I interferonopathy and CGD patients showed high interferon signatures. Pathway analysis of neonatal CGD samples revealed upregulation of systemic lupus erythematosus–like pathways.
Conclusion: Upregulation of the interferon pathway exists already at birth—not only in neonates with type I interferonopathy but also in other IEIs, including CGD. en-copyright= kn-copyright= en-aut-name=NihiraHiroshi en-aut-sei=Nihira en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaDaisuke en-aut-sei=Nakajima en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IzawaKazushi en-aut-sei=Izawa en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawashimaYusuke en-aut-sei=Kawashima en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShibataHirofumi en-aut-sei=Shibata en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KonnoRyo en-aut-sei=Konno en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashiguchiMotoko en-aut-sei=Higashiguchi en-aut-mei=Motoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoTakayuki en-aut-sei=Miyamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nishitani-IsaMasahiko en-aut-sei=Nishitani-Isa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiejimaEitaro en-aut-sei=Hiejima en-aut-mei=Eitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HondaYoshitaka en-aut-sei=Honda en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsubayashiTadashi en-aut-sei=Matsubayashi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiharaTakashi en-aut-sei=Ishihara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwataNaomi en-aut-sei=Iwata en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OhwadaYoko en-aut-sei=Ohwada en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TomotakiSeiichi en-aut-sei=Tomotaki en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawaiMasahiko en-aut-sei=Kawai en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MurakamiKosaku en-aut-sei=Murakami en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhnishiHidenori en-aut-sei=Ohnishi en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IshimuraMasataka en-aut-sei=Ishimura en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OkadaSatoshi en-aut-sei=Okada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YamashitaMotoi en-aut-sei=Yamashita en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MorioTomohiro en-aut-sei=Morio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HoshinoAkihiro en-aut-sei=Hoshino en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KaneganeHirokazu en-aut-sei=Kanegane en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ImaiKohsuke en-aut-sei=Imai en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakamuraYasuko en-aut-sei=Nakamura en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NonoyamaShigeaki en-aut-sei=Nonoyama en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UchiyamaToru en-aut-sei=Uchiyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=OnoderaMasafumi en-aut-sei=Onodera en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=IshikawaTakashi en-aut-sei=Ishikawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawaiToshinao en-aut-sei=Kawai en-aut-mei=Toshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=TakitaJunko en-aut-sei=Takita en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NishikomoriRyuta en-aut-sei=Nishikomori en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OharaOsamu en-aut-sei=Ohara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=YasumiTakahiro en-aut-sei=Yasumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= affil-num=1 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=7 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Seirei Hamamatsu General Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Nara Medical University kn-affil= affil-num=14 en-affil=Department of Pediatrics, Okayama University kn-affil= affil-num=15 en-affil=Department of Infection and Immunology, Aichi Children’s Health and Medical Center kn-affil= affil-num=16 en-affil=Department of Pediatrics, Dokkyo Medical University School of Medicine kn-affil= affil-num=17 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neonatology, Kyoto University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Pediatrics, Gifu University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=22 en-affil=Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences kn-affil= affil-num=23 en-affil=Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=24 en-affil=Laboratory of Immunology and Molecular Medicine, Advanced Research Initiative, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=25 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=26 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=27 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=28 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=29 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=30 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=31 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=32 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=33 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=34 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=35 en-affil=Department of Pediatrics and Child Health, Kurume University School of Medicine kn-affil= affil-num=36 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=37 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= en-keyword=Inborn errors of immunity kn-keyword=Inborn errors of immunity en-keyword=interferonopathy kn-keyword=interferonopathy en-keyword=signature kn-keyword=signature en-keyword=proteome kn-keyword=proteome en-keyword=dried blood spot kn-keyword=dried blood spot en-keyword=CGD kn-keyword=CGD en-keyword=WAS kn-keyword=WAS en-keyword=newborn kn-keyword=newborn en-keyword=neonate kn-keyword=neonate END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=roaf042 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recommendations for the treatment of juvenile idiopathic arthritis with oligoarthritis or polyarthritis from the 2024 update of the Japan College of Rheumatology Clinical Practice Guidelines for the management of rheumatoid arthritis including juvenile idiopathic arthritis with oligoarthritis or polyarthritis – secondary publication en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To conduct systematic reviews (SRs) and develop clinical practice guidelines (CPGs) for managing juvenile idiopathic arthritis (JIA) with oligoarthritis or polyarthritis.
Methods: The Grading of Recommendations, Assessment, Development, and Evaluation methodology was employed to carry out SRs and formulate the CPGs. An expert panel, including patients, paediatric and nonpaediatric rheumatologists, guideline specialists, and patient representatives, used the Delphi method to discuss and agree on the recommendations.
Results: Six clinical questions (CQs) on the efficacy and safety of medical treatments were evaluated. These included CQ1 on methotrexate (MTX), CQ2 on non-MTX conventional synthetic disease-modifying antirheumatic drugs, CQ3 on glucocorticoids, CQ4 on tumour necrosis factor inhibitors, CQ5 on interleukin-6 inhibitors, and CQ6 on Janus kinase inhibitors. Two randomized controlled trials were identified for CQ1, three for CQ2, two for CQ3, eight for CQ4, two for CQ5, and two for CQ6. Based on these evaluations, three strong and three conditional recommendations were established. The CPGs have been endorsed by the Japan College of Rheumatology and the Pediatric Rheumatology Association of Japan.
Conclusions: The SRs provided the necessary evidence to develop the CPGs, which are intended to guide not only paediatric but also nonpaediatric rheumatologists, caregivers, patients, and their families in treatment decision-making. en-copyright= kn-copyright= en-aut-name=MiyamaeTakako en-aut-sei=Miyamae en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkamotoNami en-aut-sei=Okamoto en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueYuzaburo en-aut-sei=Inoue en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaTomohiro en-aut-sei=Kubota en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EbatoTakasuke en-aut-sei=Ebato en-aut-mei=Takasuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IrabuHitoshi en-aut-sei=Irabu en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamedaHideto en-aut-sei=Kameda en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanekoYuko en-aut-sei=Kaneko en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuboHiroshi en-aut-sei=Kubo en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MitsunagaKanako en-aut-sei=Mitsunaga en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MoriMasaaki en-aut-sei=Mori en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakajimaAyako en-aut-sei=Nakajima en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimuraKenichi en-aut-sei=Nishimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OhkuboNaoaki en-aut-sei=Ohkubo en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SatoTomomi en-aut-sei=Sato en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SugitaYuko en-aut-sei=Sugita en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakanashiSatoshi en-aut-sei=Takanashi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaTakayuki en-aut-sei=Tanaka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UmebayashiHiroaki en-aut-sei=Umebayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamanishiShingo en-aut-sei=Yamanishi en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FusamaMie en-aut-sei=Fusama en-aut-mei=Mie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HirataShintaro en-aut-sei=Hirata en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KishimotoMitsumasa en-aut-sei=Kishimoto en-aut-mei=Mitsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KohnoMasataka en-aut-sei=Kohno en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KojimaMasayo en-aut-sei=Kojima en-aut-mei=Masayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KojimaToshihisa en-aut-sei=Kojima en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MorinobuAkio en-aut-sei=Morinobu en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=SugiharaTakahiko en-aut-sei=Sugihara en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=TanakaEiichi en-aut-sei=Tanaka en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=YajimaNobuyuki en-aut-sei=Yajima en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=YanaiRyo en-aut-sei=Yanai en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawahitoYutaka en-aut-sei=Kawahito en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HarigaiMasayoshi en-aut-sei=Harigai en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Department of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety kn-affil= affil-num=3 en-affil=Department of General Medical Science, Graduate School of Medicine, Chiba University kn-affil= affil-num=4 en-affil=Department of Pediatrics, Kagoshima Prefectural Satsunan Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kitasato University kn-affil= affil-num=6 en-affil=Department of Pediatrics and Development Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=7 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University kn-affil= affil-num=8 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=10 en-affil=Department of Allergy and Rheumatology, Chiba Children's Hospital kn-affil= affil-num=11 en-affil=Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University kn-affil= affil-num=12 en-affil=Center for Rheumatic Diseases, Mie University Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Yokohama City University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Iizuka Hospital kn-affil= affil-num=15 en-affil=Clinical Education Center For Physicians, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Pediatrics, School of Medicine, Osaka Medical and Pharmaceutical University kn-affil= affil-num=17 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Department of Pediatrics, Japanese Red Cross Otsu Hospital kn-affil= affil-num=19 en-affil=Department of Rheumatology and Infectious Diseases, Miyagi Children’s Hospital kn-affil= affil-num=20 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Pediatrics, Nippon Medical School kn-affil= affil-num=22 en-affil=Health Sciences Department of Nursing, Kansai University of International Studies kn-affil= affil-num=23 en-affil=Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital kn-affil= affil-num=24 en-affil=Department of Nephrology and Rheumatology, Kyorin University School of Medicine kn-affil= affil-num=25 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=26 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=27 en-affil=Department of Orthopedic Surgery, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=28 en-affil=Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=29 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine kn-affil= affil-num=30 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= affil-num=31 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=32 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=33 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=34 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= en-keyword=Clinical practice guidelines kn-keyword=Clinical practice guidelines en-keyword=baricitinib kn-keyword=baricitinib en-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) kn-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) en-keyword=juvenile idiopathic arthritis kn-keyword=juvenile idiopathic arthritis en-keyword=systematic review kn-keyword=systematic review END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue= article-no= start-page=244 end-page=256 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Postnatal expression of Cat-315-positive perineuronal nets in the SAMP10 mouse primary somatosensory cortex en-subtitle= kn-subtitle= en-abstract= kn-abstract=Perineuronal nets (PNNs) form at the end of the critical period of plasticity in the mouse primary somatosensory cortex. PNNs are said to have functions that control neuroplasticity and provide neuroprotection. However, it is not clear which molecules in PNNs have these functions. We have previously reported that Cat-315-positive molecules were not expressed in the PNNs of the senescence-accelerated model (SAM)P10 strain model mice at 12 months of age. To confirm whether the loss of Cat-315-positive molecules occurred early in life in SAMP10 mice, we examined Cat-315-positive PNNs in the primary somatosensory cortex during postnatal development. This research helps to elucidate the function of PNNs and the mechanism of cognitive decline associated with ageing. To confirm whether Cat-315-positive PNNs changed in an age-dependent manner in SAMP10 mice, we examined the primary somatosensory cortex at 21, 28, and 56 days after birth. We compared these results with those of senescence-accelerated mouse-resistant (SAMR) mice. In SAMP10 mice, Cat-315-positive PNNs were expressed in the primary somatosensory cortex early after birth, but their expression was significantly lower than that in SAMR1 mice. Many other molecules that calibrated the PNN were unchanged between SAMP10 and SAMR1 mice. This study revealed that the expression of the Cat-315 epitope was decreased in the primary somatosensory cortex of SAMP10 mice during postnatal development. SAMP10 mice have had histological abnormalities in their brains since early life. Furthermore, using SAMP10 will be useful in elucidating the mechanism of age-related abnormalities in brain function as well as in elucidating the function and structure of PNNs. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=Ageing kn-keyword=Ageing en-keyword=Brain function kn-keyword=Brain function en-keyword=Neuroplasticity kn-keyword=Neuroplasticity en-keyword=Neuroprotection kn-keyword=Neuroprotection en-keyword=Cognitive decline kn-keyword=Cognitive decline END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Age-related behavioural abnormalities in C57BL/6.KOR–Apoe shl mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spontaneously hyperlipidaemic (Apoeshl) mice were discovered in 1999 as mice lacking apolipoprotein E (ApoE) owing to a mutation in the Apoe gene. However, age-related behavioural changes in commercially available Apoeshl mice have not yet been clarified. The behavioural abnormalities of ApoE-deficient mice, which are genetically modified mice artificially deficient in ApoE, have been investigated in detail, and it has been reported that they can serve as a model of Alzheimer’s disease (AD). To understand whether Apoeshl mice can also serve as a murine model of AD, it is necessary to investigate age-related behavioural abnormalities in Apoeshl mice. In this study, we conducted a series of behavioural experiments on 7- and 11-month-old Apoeshl mice to investigate the behavioural abnormalities associated with ageing in Apoeshl mice. In this study, 7-month-old Apoeshl mice showed decreased body weight and grip strength compared to age-matched wild-type mice. In the open field test, 7-month-old Apoeshl mice showed increased anxiety-like behaviour compared to wild-type mice, whereas 11-month-old Apoeshl mice showed decreased anxiety-like behaviour. Moreover, Apoeshl mice aged 7 and 11 months had increased serum cholesterol levels. These results indicate that the behaviour of Apoeshl mice changes with age. However, 11-month-old Apoeshl mice did not show a decline in cognitive function or memory ability similar to murine models of AD. Our findings indicate that Apoeshl mice can be used to investigate the function of ApoE in the central nervous system. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyazakiTetsuji en-aut-sei=Miyazaki en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=age kn-keyword=age en-keyword=apolipoprotein kn-keyword=apolipoprotein en-keyword=behavioural test kn-keyword=behavioural test en-keyword=central nervous system kn-keyword=central nervous system en-keyword=mouse kn-keyword=mouse END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250222 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rearing in an envy-like environment increases anxiety-like behaviour in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Interest in the societal and psychological harm caused by widespread envy and social comparison is increasing. Envy is associated with anxiety and depression, though the mechanism by which envy affects neuropsychiatric disorders, such as depression, remains unclear. Clarifying the neurobiological basis of envy’s effects on behaviour and emotion regulation in experimental mice is essential for developing disease-prevention and treatment strategies. As mice recognize other mice in neighbouring cages, this study investigated whether they recognize neighbouring cages housed in environmentally enriched cages and suffer psychological stress due to envy. After being raised in an envy-like environment for 3 weeks, we revealed changes in the behaviour of the mice through a series of behavioural experiments. Mice raised in an envious environment showed increased body weight and anxiety-like behaviour but decreased social behaviour and serum corticosterone levels compared to control mice. Thus, mice recognize their neighbouring cages and experience psychological stress due to envy. This study revealed a part of the scientific basis for why envy increased anxiety. Using this novel experimental breeding environment, it may be possible to create an experimental animal model of anxiety disorders. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=behaviour kn-keyword=behaviour en-keyword=anxiety kn-keyword=anxiety en-keyword=mouse kn-keyword=mouse en-keyword=envy kn-keyword=envy en-keyword=rodent kn-keyword=rodent END start-ver=1.4 cd-journal=joma no-vol=2024 cd-vols= no-issue= article-no= start-page=9215607 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mice Recognise Mice in Neighbouring Rearing Cages and Change Their Social Behaviour en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mice are social animals that change their behaviour primarily in response to visual, olfactory, and auditory information from conspecifics. Rearing conditions such as cage size and colour are important factors influencing mouse behaviour. In recent years, transparent plastic cages have become standard breeding cages. The advantage of using a transparent cage is that the experimenter can observe the mouse from outside the cage without touching the cage. However, mice may recognise the environment outside the cage and change their behaviour. We speculated that mice housed in transparent cages might recognise mice in neighbouring cages. We used only male mice in this experiment. C57BL/6 mice were kept in transparent rearing cages with open lids, and the cage positions were maintained for 3 weeks. Subsequently, we examined how mice behaved toward cagemate mice, mice from neighbouring cages, and mice from distant cages. We compared the level of interest in mice using a social preference test. Similar to previous reports, subject mice showed a high degree of interest in unfamiliar mice from distant cages. By contrast, subject mice reacted to mice from neighbouring cages as familiar mice, similar to cagemate mice. This suggests that mice housed in transparent cages with open lids perceive the external environment and identify mice in neighbouring cages. Researchers should pay attention to the environment outside the mouse cage, especially for the social preference test. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=26737 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250723 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Coronary cross-sectional area stenosis severity determined using coronary CT highly correlated with coronary functional flow reserve: a pilot study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fractional flow reserve (FFR) is the gold standard for assessing the physiological significance of coronary stenosis. We examined the potential correlation between digitally measured coronary cross-sectional area stenosis using coronary computed tomography (CT) angiography and FFR. We analyzed data of 32 consecutive patients with stenoses who underwent invasive FFR determination. The cross-sectional area was assessed using 128-slice coronary detector-based spectral CT angiography. Power analysis revealed that the sample size enabled the detection of an area under the receiver operating characteristic (ROC) curve (AUC) of 0.90. FFR ≤ 0.8 and > 0.8 were defined as FFR-positive and FFR-negative, respectively. Intra- and interobserver differences were negligible. Percentage cross-sectional area stenosis was calculated as 100 × (A−B)/A, where A is the cross-sectional area at non-stenotic pre-stenotic segment and B is the cross-sectional area of the most severe stenotic lesion. AUC indicated that percentage cross-sectional area stenosis effectively discriminated between FFR-positive and FFR-negative cases, yielding a sensitivity of 0.882 and specificity of 0.933 at a cutoff of 50% area reduction, with an AUC of 0.976. Lesions with less than 45% cross-sectional area stenosis on coronary CT angiography were not FFR-positive. When ROC analysis was conducted for lesion characteristics, AUC did not significantly improve. In conclusion, the percent coronary cross-sectional area stenosis measured using coronary CT angiography distinguished between FFR-positive and FFR-negative lesions with high accuracy. The severity of coronary cross-sectional area stenosis determined using CT angiography is clinically useful for predicting FFR. en-copyright= kn-copyright= en-aut-name=KoumotoTakuto en-aut-sei=Koumoto en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KusachiShozo en-aut-sei=Kusachi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomiyaTakumi en-aut-sei=Tomiya en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiTakuya en-aut-sei=Akagi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawamuraHiroshi en-aut-sei=Kawamura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamajiHirosuke en-aut-sei=Yamaji en-aut-mei=Hirosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MurakamiTakashi en-aut-sei=Murakami en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KamikawaShigeshi en-aut-sei=Kamikawa en-aut-mei=Shigeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MurakamiMasaaki en-aut-sei=Murakami en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Radiation, Okayama Heart Clinic kn-affil= affil-num=2 en-affil=Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Division of Cardiovascular Intervention, Okayama Heart Clinic kn-affil= affil-num=4 en-affil=Division of Cardiovascular Intervention, Okayama Heart Clinic kn-affil= affil-num=5 en-affil=Division of Cardiovascular Medicine, Okayama Heart Clinic kn-affil= affil-num=6 en-affil=Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Division of Cardiovascular Medicine, Okayama Heart Clinic kn-affil= affil-num=8 en-affil=Division of Cardiovascular Medicine, Okayama Heart Clinic kn-affil= affil-num=9 en-affil=Division of Cardiovascular Intervention, Okayama Heart Clinic kn-affil= affil-num=10 en-affil=Division of Cardiovascular Intervention, Okayama Heart Clinic kn-affil= en-keyword=Ischemic heart disease kn-keyword=Ischemic heart disease en-keyword=Reversible ischemia kn-keyword=Reversible ischemia en-keyword=Coronary pressure kn-keyword=Coronary pressure en-keyword=Multi-slice CT kn-keyword=Multi-slice CT en-keyword=Coronary hemodynamics kn-keyword=Coronary hemodynamics END start-ver=1.4 cd-journal=joma no-vol=89 cd-vols= no-issue=8 article-no= start-page=1217 end-page=1226 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microbial biotransformation of proteins into amino acids in unpolished Thai and polished Japanese rice varieties cultivated with distinct industrial strains of koji mold en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported the cultivation of industrial koji mold strains to produce unpolished Thai-colored rice kojis. These kojis, along with those made from unpolished Thai white rice and polished Japanese white rice, showed increased polyphenol content after cultivation, with the highest levels observed in unpolished Thai-colored rice kojis. In this study, an increase in both proteinogenic and non-proteinogenic amino acid contents, particularly γ-aminobutyric acid (GABA) content, was observed in both unpolished Thai and polished Japanese rice kojis, suggesting the ability of koji mold in the biotransformation of proteins. This increase was almost comparable even when using different rice varieties; in contrast, it varied depending on the koji mold strain used. The observed increase in both polyphenol and functional amino acid contents, especially GABA content, highlights the potential of unpolished Thai and polished Japanese rice kojis, particularly unpolished Thai-colored rice koji, as multifunctional materials, benefiting from polyphenol and amino acid functionalities. en-copyright= kn-copyright= en-aut-name=JitpakdeeJirayu en-aut-sei=Jitpakdee en-aut-mei=Jirayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoKazunari en-aut-sei=Ito en-aut-mei=Kazunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaninoYuka en-aut-sei=Tanino en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeuchiHayato en-aut-sei=Takeuchi en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamashitaHideyuki en-aut-sei=Yamashita en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakagawaTakuro en-aut-sei=Nakagawa en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NitodaTeruhiko en-aut-sei=Nitoda en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanzakiHiroshi en-aut-sei=Kanzaki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Industrial Technology Center of Okayama Prefecture kn-affil= affil-num=3 en-affil=Industrial Technology Center of Okayama Prefecture kn-affil= affil-num=4 en-affil=Industrial Technology Center of Okayama Prefecture kn-affil= affil-num=5 en-affil=Higuchi Matsunosuke Shoten Co., Ltd. kn-affil= affil-num=6 en-affil=Higuchi Matsunosuke Shoten Co., Ltd. kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Amino acid kn-keyword=Amino acid en-keyword=GABA kn-keyword=GABA en-keyword=koji mold kn-keyword=koji mold en-keyword=rice koji kn-keyword=rice koji en-keyword=Thai-colored rice kn-keyword=Thai-colored rice END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=23 article-no= start-page=3243 end-page=3248 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful Treatment for Life Threatening Recurrent Non-traumatic Rectus Sheath Hematoma in a Case with Microscopic Polyangiitis with Rapidly Progressive Glomerulonephritis en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 68-year-old woman was admitted to our hospital because of a rapid progression of renal dysfunction with positive myeloperoxidase antineutrophil cytoplasmic antibody and was diagnosed with rapidly progressive glomerulonephritis associated with microscopic polyangiitis (MPA). Severe right rectus sheath hematoma (RSH) bleeding from the inferior epigastric artery developed after starting hemodialysis, which required 4 transarterial embolizations due to recurrent bleeding. After additional treatment with methylprednisolone pulse therapy and rituximab, no rebleeding occurred. Although the giant hematoma reached the pelvis, it shrank spontaneously without any intervention. Nontraumatic RSH should therefore be considered when treating patients with multiple risk factors. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimotoShiho en-aut-sei=Morimoto en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TerajimaYuya en-aut-sei=Terajima en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkamotoShugo en-aut-sei=Okamoto en-aut-mei=Shugo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=rectus sheath hematoma kn-keyword=rectus sheath hematoma en-keyword=microscopic polyangiitis kn-keyword=microscopic polyangiitis en-keyword=hemodialysis kn-keyword=hemodialysis END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=30648 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the maturation of the cardiomyocytes. This study aimed to improve the differentiation and subsequent maturation of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunocytochemistry, transmission electron microscopy, calcium imaging and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and MYL2) in both groups, with higher protein expression in the stretch group. Additionally, structural maturation of iPS-CMs in the stretch group was notably better than in the control group. A significant increase in the contractility and calcium cycle of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturation of iPS-CMs co-cultured with HGF. en-copyright= kn-copyright= en-aut-name=WangMengxue en-aut-sei=Wang en-aut-mei=Mengxue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IdeiHarumi en-aut-sei=Idei en-aut-mei=Harumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangChen en-aut-sei=Wang en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiangYin en-aut-sei=Liang en-aut-mei=Yin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiuYun en-aut-sei=Liu en-aut-mei=Yun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsudaYusuke en-aut-sei=Matsuda en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nursing, School of Life and Health Sciences, HuZhou College kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Human induced pluripotent stem cell kn-keyword=Human induced pluripotent stem cell en-keyword=Cardiomyocyte kn-keyword=Cardiomyocyte en-keyword=Human gingival fibroblast kn-keyword=Human gingival fibroblast en-keyword=Mechanical stretching kn-keyword=Mechanical stretching END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary tumour resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): a randomised clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Several prospective studies have evaluated the benefit of primary tumour resection (PTR) in de novo Stage IV breast cancer (BC) patients, but it remains controversial. We aimed to investigate whether PTR improves the survival of de novo stage IV BC patients.
Methods: De novo stage IV BC patients were enrolled in the first registration and received systemic therapies according to clinical subtypes. Patients without progression after primary systemic therapy for 3 months were randomly assigned 1:1 to systemic therapy alone (arm A) or PTR plus systemic therapy (arm B). The primary endpoint was overall survival (OS), and the secondary endpoints included local relapse-free survival (LRFS).
Results: Five hundred seventy patients were enrolled between May 5, 2011, and May 31, 2018. Of these, 407 were randomised to arm A (N = 205) or arm B (N = 202). The median follow-up time of all randomised patients was 60 months. The difference in OS was not statistically significant (HR 0.86 90% CI 0.69–1.07, one-sided p = 0.13). Median OS was 69 months (arm A) and 75 months (arm B). In the subgroup analysis, PTR was associated with improved OS in pre-menopausal patients, or those with single-organ metastasis. LRFS in arm B was significantly longer than that in arm A (median LRFS 20 vs. 63 months: HR 0.42, 95% CI 0.33–0.53, p < 0.0001). There were no treatment-related deaths.
Conclusions: PTR did not prolong OS. However, it improved local control and might benefit a subset of patients, such as those with premenopausal status or with single-organ metastasis. It also improved local relapse-free survival (LRFS), which is a clinically meaningful outcome in trials of systemic therapy.
Clinical trial registration: UMIN Clinical Trials Registry (UMIN000005586); Japan Registry of Clinical Trials (jRCTs031180151). en-copyright= kn-copyright= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AogiKenjiro en-aut-sei=Aogi en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanagidaYasuhiro en-aut-sei=Yanagida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuneizumiMichiko en-aut-sei=Tsuneizumi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoNaohito en-aut-sei=Yamamoto en-aut-mei=Naohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoHiroshi en-aut-sei=Matsumoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SutoAkihiko en-aut-sei=Suto en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeKenichi en-aut-sei=Watanabe en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraoMichiko en-aut-sei=Harao en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KanbayashiChizuko en-aut-sei=Kanbayashi en-aut-mei=Chizuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ItohMitsuya en-aut-sei=Itoh en-aut-mei=Mitsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KadoyaTakayuki en-aut-sei=Kadoya en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AnanKeisei en-aut-sei=Anan en-aut-mei=Keisei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaShigeto en-aut-sei=Maeda en-aut-mei=Shigeto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SasakiKeita en-aut-sei=Sasaki en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OgawaGakuto en-aut-sei=Ogawa en-aut-mei=Gakuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SajiShigehira en-aut-sei=Saji en-aut-mei=Shigehira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FukudaHaruhiko en-aut-sei=Fukuda en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Okayama University Hospital kn-affil= affil-num=2 en-affil=Cancer Institute Hospital kn-affil= affil-num=3 en-affil=National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Shizuoka General Hospital kn-affil= affil-num=5 en-affil=Gunma Prefectural Cancer Center kn-affil= affil-num=6 en-affil=Chiba Prefectural Cancer Center kn-affil= affil-num=7 en-affil=Saitama Prefectural Cancer Center kn-affil= affil-num=8 en-affil=National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Hokkaido Cancer Center kn-affil= affil-num=10 en-affil=Jichi Medical University Hospital kn-affil= affil-num=11 en-affil=Niigata Prefectural Cancer Center kn-affil= affil-num=12 en-affil=Hiroshima City Hiroshima Citizen’s Hospital kn-affil= affil-num=13 en-affil=Hiroshima University Hospital kn-affil= affil-num=14 en-affil=Kitakyushu Municipal Medical Center kn-affil= affil-num=15 en-affil=Nagasaki Municipal Medical Center kn-affil= affil-num=16 en-affil=National Cancer Center Hospital kn-affil= affil-num=17 en-affil=National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Fukushima Medical University kn-affil= affil-num=19 en-affil=National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Aichi Cancer Center Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=77 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of amyloid and tau positivity on longitudinal brain atrophy in cognitively normal individuals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Individuals on the preclinical Alzheimer's continuum, particularly those with both amyloid and tau positivity (A + T +), display a rapid cognitive decline and elevated disease progression risk. However, limited studies exist on brain atrophy trajectories within this continuum over extended periods.
Methods This study involved 367 ADNI participants grouped based on combinations of amyloid and tau statuses determined through cerebrospinal fluid tests. Using longitudinal MRI scans, brain atrophy was determined according to the whole brain, lateral ventricle, and hippocampal volumes and cortical thickness in AD-signature regions. Cognitive performance was evaluated with the Preclinical Alzheimer's Cognitive Composite (PACC). A generalized linear mixed-effects model was used to examine group × time interactions for these measures. In addition, progression risks to mild cognitive impairment (MCI) or dementia were compared among the groups using Cox proportional hazards models.
Results A total of 367 participants (48 A + T + , 86 A + T − , 63 A − T + , and 170 A − T − ; mean age 73.8 years, mean follow-up 5.1 years, and 47.4% men) were included. For the lateral ventricle and PACC score, the A + T − and A + T + groups demonstrated statistically significantly greater volume expansion and cognitive decline over time than the A − T − group (lateral ventricle: β = 0.757 cm3/year [95% confidence interval 0.463 to 1.050], P < .001 for A + T − , and β = 0.889 cm3/year [0.523 to 1.255], P < .001 for A + T + ; PACC: β = − 0.19 /year [− 0.36 to − 0.02], P = .029 for A + T − , and β = − 0.59 /year [− 0.80 to − 0.37], P < .001 for A + T +). Notably, the A + T + group exhibited additional brain atrophy including the whole brain (β = − 2.782 cm3/year [− 4.060 to − 1.504], P < .001), hippocampus (β = − 0.057 cm3/year [− 0.085 to − 0.029], P < .001), and AD-signature regions (β = − 0.02 mm/year [− 0.03 to − 0.01], P < .001). Cox proportional hazards models suggested an increased risk of progressing to MCI or dementia in the A + T + group versus the A − T − group (adjusted hazard ratio = 3.35 [1.76 to 6.39]).
Conclusions In cognitively normal individuals, A + T + compounds brain atrophy and cognitive deterioration, amplifying the likelihood of disease progression. Therapeutic interventions targeting A + T + individuals could be pivotal in curbing brain atrophy, cognitive decline, and disease progression. en-copyright= kn-copyright= en-aut-name=FujishimaMotonobu en-aut-sei=Fujishima en-aut-mei=Motonobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawasakiYohei en-aut-sei=Kawasaki en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsudaHiroshi en-aut-sei=Matsuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Radiology, Kumagaya General Hospital kn-affil= affil-num=2 en-affil=Department of Biostatistics, Graduate School of Medicine, Saitama Medical University kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Biofunctional Imaging, Fukushima Medical University kn-affil= en-keyword=Preclinical kn-keyword=Preclinical en-keyword=Alzheimer’s disease kn-keyword=Alzheimer’s disease en-keyword=Longitudinal MRI kn-keyword=Longitudinal MRI en-keyword=Tau kn-keyword=Tau en-keyword=Amyloid-β kn-keyword=Amyloid-β END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250714 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Week 2 remission with vedolizumab as a predictor of long-term remission in patients with ulcerative colitis: a multicenter, retrospective, observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims Vedolizumab (VDZ), a gut-selective monoclonal antibody for ulcerative colitis (UC) treatment, has no established biomarkers or clinical features that predict long-term remission. Week 2 remission, a potential predictor of long-term remission, could inform maintenance treatment strategy.
Methods This retrospective, observational chart review included patients with UC in Japan who initiated VDZ between December 2018 and February 2020. Outcome measures included 14- and 54-week remission rates in patients with week 2 and non-week 2 remission (remission by week 14), 54-week remission rates in patients with week 14 remission and primary nonresponse, and predictive factors of week 2 and week 54 remission (logistic regression).
Results Overall, 332 patients with UC (176 biologic-naïve and 156 biologic-non-naïve) were included. Significantly more biologic-naïve than biologic-non-naïve patients achieved week 2 remission (36.9% vs. 28.2%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.05–1.94; P=0.0224). Week 54 remission rates were significantly different between week 14 remission and primary nonresponse (both groups: P<0.0001), and between week 2 and non-week 2 remission (all patients: OR, 2.41; 95% CI, 1.30–4.48; P=0.0052; biologic-naïve patients: OR, 2.40; 95% CI, 1.10–5.24; P=0.0280). Week 2 remission predictors were male sex, no anti-tumor necrosis factor alpha exposure, and normal/mild endoscopic findings. Week 54 remission was significantly associated with week 2 remission and no tacrolimus use.
Conclusions Week 2 remission with VDZ is a predictor of week 54 remission in patients with UC. Week 2 may be used as an evaluation point for UC treatment decisions. (Japanese Registry of Clinical Trials: jRCT-1080225363) en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FernandezJovelle L en-aut-sei=Fernandez en-aut-mei=Jovelle L kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Colitis, ulcerative kn-keyword=Colitis, ulcerative en-keyword=Inflammatory bowel diseases kn-keyword=Inflammatory bowel diseases en-keyword=Japan kn-keyword=Japan en-keyword=Vedolizumab kn-keyword=Vedolizumab END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The duration of prior anti-tumor necrosis factor agents is associated with the effectiveness of vedolizumab in patients with ulcerative colitis: a real-world multicenter retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims Previous literature suggests that the response of patients with ulcerative colitis to vedolizumab may be affected by previous biologic therapy exposure. This real-world study evaluated vedolizumab treatment effectiveness in biologicnon-naïve patients.
Methods This was a multicenter, retrospective, observational chart review of records from 16 hospitals in Japan (December 1, 2018, to February 29, 2020). Included patients who had ulcerative colitis, were aged ≥ 20 years, and received at least 1 dose of vedolizumab. Outcomes included clinical remission rates from weeks 2 to 54 according to prior biologic exposure status and factors associated with clinical remission up to week 54.
Results A total of 370 eligible patients were included. Clinical remission rates were significantly higher in biologic-naïve (n=197) than in biologic-non-naïve (n=173) patients for weeks 2 to 54 of vedolizumab treatment. Higher clinical remission rates up to week 54 were significantly associated with lower disease severity (partial Mayo score ≤ 4, P= 0.001; albumin ≥ 3.0, P= 0.019) and the duration of prior anti-tumor necrosis factor α (anti-TNFα) therapy (P= 0.026). Patients with anti-TNFα therapy durations of < 3 months, 3 to < 12 months, and ≥ 12 months had clinical remission rates of 28.1%, 32.7%, and 60.0%, respectively (P= 0.001 across groups).
Conclusions The effectiveness of vedolizumab in biologic-non-naïve patients was significantly influenced by duration of prior anti-TNFα therapy. (Japanese Registry of Clinical Trials: jRCT-1080225363) en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FernandezJovelle L en-aut-sei=Fernandez en-aut-mei=Jovelle L kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=6 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Tumor necrosis factor-alpha kn-keyword=Tumor necrosis factor-alpha en-keyword=Real-world evidence kn-keyword=Real-world evidence en-keyword=Colitis kn-keyword=Colitis en-keyword=ulcerative kn-keyword=ulcerative en-keyword=Vedolizumab kn-keyword=Vedolizumab en-keyword=Sequencing kn-keyword=Sequencing END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=6 article-no= start-page=1435 end-page=1445 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250515 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-World Effectiveness and Safety of Vedolizumab in Patients ≥ 70 Versus < 70 Years With Ulcerative Colitis: Multicenter Retrospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Vedolizumab (VDZ) is often used in older patients with ulcerative colitis (UC) in clinical practice; however, real-world evidence is still limited, including in those with late-onset UC.
Methods: This post hoc analysis of a multicenter, retrospective, observational chart review, enrolling 370 patients with UC receiving VDZ between December 2018 and February 2020, compared effectiveness and safety of VDZ among patients ≥ 70 (n = 40) versus < 70 years (n = 330), and among patients ≥ 70 years with and without late-onset UC (age at disease onset: ≥ 70 [n = 13] versus < 70 years [n = 26]).
Results: There were no differences between patients ≥ 70 and < 70 years in clinical remission rates (week 6: 57.5% vs. 47.6%, p = 0.9174; week 14: 62.5% vs. 54.8%, p = 0.1317; week 54: 47.5% vs. 46.4%, p = 0.8149), primary nonresponse (10.0% vs. 15.5%, p = 0.6248), loss of response (12.5% vs. 9.4%, p = 0.5675), or overall safety. Among patients ≥ 70 years, the incidence of adverse drug reactions was numerically greater in those with concomitant corticosteroids than in those without. For older patients with and without late-onset UC, week 54 remission rates were 23.1% versus 57.7% (p = 0.0544); surgery was reported in 3/13 versus 2/26 patients and hospitalization in 5/13 versus 6/26 patients. One death was reported in patients with late-onset UC.
Conclusions: VDZ effectiveness and safety were similar in patients ≥ 70 and < 70 years; VDZ may be a suitable treatment option for patients ≥ 70 years with UC. Patients with late-onset UC tended to have more frequent surgery/hospitalization and lower effectiveness than those without, possibly necessitating greater caution when using VDZ.
Trial Registration: Japanese Registry of Clinical Trials registration number: jRCT-1080225363 en-copyright= kn-copyright= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FernandezJovelle L. en-aut-sei=Fernandez en-aut-mei=Jovelle L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HiroseLisa en-aut-sei=Hirose en-aut-mei=Lisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=2 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=22 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=elderly kn-keyword=elderly en-keyword=inflammatory bowel diseases kn-keyword=inflammatory bowel diseases en-keyword=onset age kn-keyword=onset age en-keyword=vedolizumab kn-keyword=vedolizumab END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Factors affecting 1-year persistence with vedolizumab for ulcerative colitis: a multicenter, retrospective real-world study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response.
Methods In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled.
Results Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00–7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13–0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response.
Conclusions Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence. en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FernandezJovelle L. en-aut-sei=Fernandez en-aut-mei=Jovelle L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=DeguchiHisato en-aut-sei=Deguchi en-aut-mei=Hisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=22 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Colitis, ulcerative kn-keyword=Colitis, ulcerative en-keyword=Inflammatory bowel diseases kn-keyword=Inflammatory bowel diseases en-keyword=Japan kn-keyword=Japan en-keyword=Vedolizumab kn-keyword=Vedolizumab en-keyword=Medication persistence kn-keyword=Medication persistence END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=30648 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the maturation of the cardiomyocytes. This study aimed to improve the differentiation and subsequent maturation of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunocytochemistry, transmission electron microscopy, calcium imaging and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and MYL2) in both groups, with higher protein expression in the stretch group. Additionally, structural maturation of iPS-CMs in the stretch group was notably better than in the control group. A significant increase in the contractility and calcium cycle of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturation of iPS-CMs co-cultured with HGF. en-copyright= kn-copyright= en-aut-name=WangMengxue en-aut-sei=Wang en-aut-mei=Mengxue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IdeiHarumi en-aut-sei=Idei en-aut-mei=Harumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangChen en-aut-sei=Wang en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiangYin en-aut-sei=Liang en-aut-mei=Yin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiuYun en-aut-sei=Liu en-aut-mei=Yun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsudaYusuke en-aut-sei=Matsuda en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nursing, School of Life and Health Sciences, HuZhou College kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Human induced pluripotent stem cell kn-keyword=Human induced pluripotent stem cell en-keyword=Cardiomyocyte kn-keyword=Cardiomyocyte en-keyword=Human gingival fibroblast kn-keyword=Human gingival fibroblast en-keyword=Mechanical stretching kn-keyword=Mechanical stretching END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue= article-no= start-page=1477 end-page=1486 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predictive Value of Tumor ERCC1 Expression for Treatment Outcomes After Adjuvant Chemotherapy in Patients with Completely Resected Non-Small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To evaluate the predictive value of tumor expression of the excision repair cross-complementation group 1 gene (ERCC1) for the treatment outcomes after platinum-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC).
Methods: In this study, we conducted immunohistochemical analysis using a mouse monoclonal anti-ERCC1 antibody (clone 8F1) of operative specimens obtained from 238 patients enrolled in the SLCG0401 study which compared paclitaxel plus carboplatin (CBDCA+PTX) with uracil-tegafur (UFT) as adjuvant chemotherapy for stage IB-IIIA NSCLC. The overall survival (OS) of the patients was compared according to the ERCC1 expression status and adjuvant chemotherapy employed.
Results: Of the 238 specimens, 102 (42.9%) showed a positive result for ERCC1 expression. There were no significant differences in the patient characteristics or OS between the tumor ERCC1-positive and -negative patient groups. Among the patients with ERCC1-negative tumors, there was no significant difference in the survival between patient groups treated with CBDCA+PTX and UFT (HR=0.932, 95% CI: 0.52– 1.67, p=0.814). However, among the patients with ERCC1-positive tumors, CBDCA+PTX treatment tended to yield an inferior outcome, in terms of the OS, as compared with UFT treatment (HR=1.852, 95% CI: 0.92– 3.73, p=0.080). Multivariate analysis showed that ERCC1 expression was not an independent predictor of the OS following CBDCA+PTX treatment in completely resected NSCLC patients.
Conclusion: In completely resected NSCLC patients with positive tumor ERCC1 expression, adjuvant CBDCA+PTX treatment tended to yield an inferior outcome as compared with UFT treatment in terms of the OS. However, immunohistochemical analysis with the 8F1 antibody cannot be used for clinical decision making at this point. en-copyright= kn-copyright= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaishoShinsuke en-aut-sei=Saisho en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkumuraNorihito en-aut-sei=Okumura en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraHiroshige en-aut-sei=Nakamura en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=5 en-affil=Division of General Thoracic Surgery and Breast and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Tottori University kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Kyoto University Graduate School of Medicine kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=postoperative adjuvant chemotherapy kn-keyword=postoperative adjuvant chemotherapy en-keyword=platinum-based chemotherapy kn-keyword=platinum-based chemotherapy en-keyword=excision repair crosscomplementation group 1 gene kn-keyword=excision repair crosscomplementation group 1 gene en-keyword=survival kn-keyword=survival END start-ver=1.4 cd-journal=joma no-vol=409 cd-vols= no-issue=1 article-no= start-page=356 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Subjective global assessment for nutritional screening and its impact on surgical outcomes: A prospective study in older patients with colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Our perioperative management center provides preoperative intervention and functional and nutritional assessments for colorectal cancer patients aged over 75 years. This study evaluated the associations of preoperative nutritional status with postoperative outcomes and prognosis in colorectal cancer patients aged 75 years or older.
Methods This was a prospective, observational study of 71 colorectal cancer patients aged 75 years or older who underwent surgery between July 2020 and September 2022. The Subjective Global Assessment (SGA) was evaluated as a nutritional index. The patients were classified into three groups: SGA-A (well nourished), B (moderately malnourished), and C (severely malnourished), and the correlations with postoperative outcomes and prognosis were examined.
Results The median age of the 71 patients (34 males, 37 females) was 78 (75–92) years, and their median body mass index (BMI) was 22.3 (13.4–31.9) kg/m2. Forty-eight patients had colon cancer, and 23 had rectal cancer. On the SGA, 28 patients were SGA-A, 25 SGA-B, and 18 SGA-C. The SGA-B/C group had significantly higher BMI (p < 0.01) and more ICU admissions (p = 0.02). The G8 score was significantly lower (p = 0.03) in the SGA-B/C group, suggesting coexisting functional decline. In terms of postoperative outcomes, the SGA-B/C group had a significantly longer postoperative hospital stay (p = 0.04). The 3-year OS rates for all stages were 100% in the SGA-A group and 49.7% in the SGA-B/C group (p = 0.03), while the 3-year OS rates for patients excluding Stage IV were 100% in the SGA-A group and 68.5% in the SGA-B/C group, not significantly different (p = 0.14). The 3-year RFS rate was 95.5% in the SGA-A group and 65.3% in the SGA-B/C group (p = 0.15).
Conclusion The SGA is a promising nutritional index associated with short-term outcomes in older patients undergoing colorectal cancer surgery. The SGA can be assessed in a few minutes during an outpatient visit, making it useful for routine clinical use. en-copyright= kn-copyright= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamuraRie en-aut-sei=Tamura en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuokaYoshikazu en-aut-sei=Matsuoka en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=10 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=11 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Subjective global assessment kn-keyword=Subjective global assessment en-keyword=Colorectal cancer kn-keyword=Colorectal cancer en-keyword=Older patients kn-keyword=Older patients en-keyword=Surgical outcome kn-keyword=Surgical outcome END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=5 article-no= start-page=271 end-page=277 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240329 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Japan MSA registry: A multicenter cohort study of multiple system atrophy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and various motor symptoms. While MSA-C (cerebellar type) predominates in East Asia, MSA-P (parkinsonian type) predominates in Europe and North America. This nationwide patient registry aimed to (1) conduct a prospective natural history study of MSA in Japan, (2) facilitate patient recruitment for clinical trials, and (3) deposit bioresources and clinical information in a biobank.
Methods: Thirteen institutions participated in this study. Clinical information was obtained by neurologists from the patients visiting the hospital every 12 months to assess the UMSARS Part 2 scores and by telephone interviews by nurses every 6 months to assess UMSARS Part 1 scores and to determine whether clinical events had occurred.
Results: Demographic data from 329 MSA patients (216 MSA-C and 113 MSA-P) were analyzed. The mean age at symptom onset was 58.2 years (standard deviation, 8.9); the mean duration of symptoms at enrollment was 3.5 years (standard deviation, 2.2). The mean 12-month changes in the UMSARS Part 1 and Part 2 scores were 7.9 (standard deviation, 5.6) and 6.4 (standard deviation, 5.9), respectively. The patient registry proved useful in recruiting participants for clinical trials, including those with gene variants. Clinical information and biospecimens were deposited in a biobank.
Discussion: The study highlighted the importance of telephone interviews in minimizing drop-out rates in natural history studies and demonstrated similar MSA progression rates across populations. The deposited bioresources are available to researchers upon request, aiming to contribute to future MSA researches. en-copyright= kn-copyright= en-aut-name=ChikadaAyaka en-aut-sei=Chikada en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MizusawaHidehiro en-aut-sei=Mizusawa en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakahashiYuji en-aut-sei=Takahashi en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatsunoMasahisa en-aut-sei=Katsuno en-aut-mei=Masahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraKazuhiro en-aut-sei=Hara en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OnoderaOsamu en-aut-sei=Onodera en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IshiharaTomohiko en-aut-sei=Ishihara en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TadaMasayoshi en-aut-sei=Tada en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KuwabaraSatoshi en-aut-sei=Kuwabara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SugiyamaAtsuhiko en-aut-sei=Sugiyama en-aut-mei=Atsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamanakaYoshitaka en-aut-sei=Yamanaka en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakahashiRyosuke en-aut-sei=Takahashi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SawamotoNobukatsu en-aut-sei=Sawamoto en-aut-mei=Nobukatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SakatoYusuke en-aut-sei=Sakato en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IshimotoTomoyuki en-aut-sei=Ishimoto en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HanajimaRitsuko en-aut-sei=Hanajima en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=WatanabeYasuhiro en-aut-sei=Watanabe en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TakigawaHiroshi en-aut-sei=Takigawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=AdachiTadashi en-aut-sei=Adachi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TakashimaHiroshi en-aut-sei=Takashima en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=HigashiKeiko en-aut-sei=Higashi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KiraJunichi en-aut-sei=Kira en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=YabeIchiro en-aut-sei=Yabe en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=MatsushimaMasaaki en-aut-sei=Matsushima en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=OgataKatsuhisa en-aut-sei=Ogata en-aut-mei=Katsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=IshikawaKinya en-aut-sei=Ishikawa en-aut-mei=Kinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=NishidaYoichiro en-aut-sei=Nishida en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=IshiguroTaro en-aut-sei=Ishiguro en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OzakiKokoro en-aut-sei=Ozaki en-aut-mei=Kokoro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NagataTetsuya en-aut-sei=Nagata en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=12 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=13 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=15 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=16 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=17 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Human Health Sciences, Kyoto University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=22 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=23 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=24 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=25 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=26 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=27 en-affil=Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=28 en-affil=Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=29 en-affil=Department of Neurology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=30 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=31 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=32 en-affil=Department of Neurology, Higashi-Saitama National Hospital kn-affil= affil-num=33 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=34 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=35 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=36 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=37 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=38 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=multicenter cohort study kn-keyword=multicenter cohort study en-keyword=multiple system atrophy kn-keyword=multiple system atrophy en-keyword=natural history kn-keyword=natural history en-keyword=patient registry kn-keyword=patient registry END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=4 article-no= start-page=e70172 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevalence, Characteristics, and Arrhythmogenic Substrate of Mitral Annular Disjunction Assessed by Cardiac Magnetic Resonance Imaging in Patients With Apparently Idiopathic Ventricular Arrhythmia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Mitral annular disjunction (MAD) is linked to an increased risk of sudden cardiac death, but its association with ventricular arrhythmias (VAs) in Japanese patients is unclear.
Methods: We retrospectively analyzed 129 Japanese patients with VAs and no overt structural heart disease who underwent echocardiography and cardiac MRI.
Results: MAD was diagnosed in 7.0%, and in 14% of patients with VAs originating from the mitral valve apparatus. MAD was significantly associated with multifocal VAs, late gadolinium enhancement in the papillary muscles, and greater mitral regurgitation.
Conclusion: MAD may be an important arrhythmogenic substrate in apparently idiopathic VAs among Japanese patients. en-copyright= kn-copyright= en-aut-name=AsadaSaori en-aut-sei=Asada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasudaTakuro en-aut-sei=Masuda en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UeokaAkira en-aut-sei=Ueoka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=2 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=6 en-affil=Department of Cardiology, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= en-keyword=arrhythmic mitral valve prolapses kn-keyword=arrhythmic mitral valve prolapses en-keyword=idiopathic ventricular arrhythmia kn-keyword=idiopathic ventricular arrhythmia en-keyword=late gadolinium enhancement kn-keyword=late gadolinium enhancement en-keyword=mitral annular disjunction kn-keyword=mitral annular disjunction en-keyword=multifocal ventricular arrhythmia kn-keyword=multifocal ventricular arrhythmia END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=3 article-no= start-page=79 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of the expression of 5‑FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S‑1 adjuvant chemotherapy: Follow‑up results of the Setouchi Lung Cancer Group Study 1201 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Managing elderly patients presents several challenges because of age‑related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non‑small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5‑fluorouracil (5‑FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5‑FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S‑1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5‑FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross‑complementation group 1 (ERCC1), were assessed via quantitative reverse‑transcription PCR assays in 89 elderly patients (≥75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S‑1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that TS expression decreased significantly with aging, especially in the age group ≥75. In the SCLG1201 trial, univariate analysis revealed that EGFR upregulation and TS downregulation were correlated with favorable recurrence‑free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. EGFR mutations were associated with upregulation of DPD and EGFR, and downregulation of TS and ERCC1. In conclusion, although pathological stage is an independent prognostic factor for survival, EGFR upregulation and TS downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S‑1 adjuvant chemotherapy. The age‑related decrease in TS expression supports the potential benefit of 5‑FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results. en-copyright= kn-copyright= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkumuraNorihito en-aut-sei=Okumura en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHiroyuki en-aut-sei=Suzuki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GembaKenicehi en-aut-sei=Gemba en-aut-mei=Kenicehi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SanoIsao en-aut-sei=Sano en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujinagaTakuji en-aut-sei=Fujinaga en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaMasafumi en-aut-sei=Kataoka en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerasakiYasuhiro en-aut-sei=Terasaki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KataokaKazuhiko en-aut-sei=Kataoka en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KosakaShinji en-aut-sei=Kosaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakamuraHiroshige en-aut-sei=Nakamura en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamashitaYoshinori en-aut-sei=Yamashita en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakahashiYuta en-aut-sei=Takahashi en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=SatoHiroki en-aut-sei=Sato en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MoritaSatoshi en-aut-sei=Morita en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MatsuoKeitaro en-aut-sei=Matsuo en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=SakamotoJunichi en-aut-sei=Sakamoto en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Chest Surgery, Fukushima Medical University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima 720‑0001, Japan; 8Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center kn-affil= affil-num=10 en-affil=Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Surgery, Saga Medical Center Koseikan kn-affil= affil-num=12 en-affil=Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=13 en-affil=Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=14 en-affil=Department of Thoracic Surgery, Shimane Prefectural Central Hospital kn-affil= affil-num=15 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=16 en-affil=Department of Thoracic Surgery, National Hospital Organization Yamaguchi‑Ube Medical Center kn-affil= affil-num=17 en-affil=Department of Thoracic Surgery, Shimonoseki City Hospital kn-affil= affil-num=18 en-affil=Division of General Thoracic Surgery, Tottori University Hospital kn-affil= affil-num=19 en-affil=Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=20 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=23 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=24 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=26 en-affil=Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine kn-affil= affil-num=27 en-affil=Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute kn-affil= affil-num=28 en-affil=Tokai Central Hospital kn-affil= affil-num=29 en-affil=Department of Thoracic Surgery, Kyoto University Hospital kn-affil= affil-num=30 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=non‑small cell lung cancer kn-keyword=non‑small cell lung cancer en-keyword=elderly patients kn-keyword=elderly patients en-keyword=adjuvant chemotherapy kn-keyword=adjuvant chemotherapy en-keyword=S‑1 kn-keyword=S‑1 en-keyword=EGFR kn-keyword=EGFR en-keyword=TP kn-keyword=TP en-keyword=TS kn-keyword=TS en-keyword=OPRT kn-keyword=OPRT en-keyword=ERCC1 kn-keyword=ERCC1 en-keyword=DPD kn-keyword=DPD END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=30 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250529 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Non-convulsive status epilepticus as a cause of delayed emergence after a thoracic surgery: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Non-convulsive status epilepticus (NCSE) is an electrical discharge which occurs without prominent motor symptoms. NCSE is one of the causes of delayed emergence from anesthesia; however, as far as we know, previous reports of postoperative NCSE were related to patients after neurological surgery. Herein, we report a case of an elderly male who developed initial NCSE after thoracic surgery. The patient remained unresponsive and developed hemiplegia after lung resection, and then the symptoms fluctuated between better and worse. Metabolic disorders and stroke were ruled out, and NCSE was diagnosed by magnetic resonance imaging (MRI) and electroencephalography (EEG). NCSE occurred in a patient who had no predisposing factors or underwent non-neurological surgery. When anesthesiologists encounter delayed emergence, NCSE should be listed as a differential diagnosis and examined by MRI and EEG. en-copyright= kn-copyright= en-aut-name=IritaniYusuke en-aut-sei=Iritani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaniMakiko en-aut-sei=Tani en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IgaShinji en-aut-sei=Iga en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Anesthesiology, Okayama Red Cross Hospital kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Non-convulsive status epilepticus kn-keyword=Non-convulsive status epilepticus en-keyword=Delayed emergence kn-keyword=Delayed emergence en-keyword=Anesthesia kn-keyword=Anesthesia en-keyword=Electroencephalography kn-keyword=Electroencephalography en-keyword=Postoperative complication kn-keyword=Postoperative complication END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=e70146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Gastric Atypical Lipomatous Tumor/Well‐Differentiated Liposarcoma With Endoscopic Morphological Changes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Atypical lipomatous tumor/well-differentiated liposarcoma is a locally aggressive mesenchymal neoplasm composed of adipocytes and stromal cells. Gastric cases are exceedingly rare, and their malignant potential remains unclear. We report a case of a woman in her 60s who was found to have multiple submucosal tumor-like lesions of the stomach. Over time, the tumors increased in size, requiring a laparoscopic partial gastrectomy. Histological examination revealed a tumor composed of both fatty tissue and fibrous stroma with nuclear atypia. Immunohistochemistry showed positivity for CDK4 and MDM2, and fluorescence in situ hybridization confirmed MDM2 amplification, leading to a diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma. This case presented an unusual gastric manifestation, with multiple submucosal tumor-like lesions on endoscopy and exhibiting progressive morphological changes over several years. en-copyright= kn-copyright= en-aut-name=OmoteRika en-aut-sei=Omote en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmoteShizuma en-aut-sei=Omote en-aut-mei=Shizuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SonobeHiroshi en-aut-sei=Sonobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamanoRyosuke en-aut-sei=Hamano en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaShinya en-aut-sei=Otsuka en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InagakiMasaru en-aut-sei=Inagaki en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Fukuyama Minami Hospital kn-affil= affil-num=3 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Gastroenterology, NHO Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=atypical lipomatous tumor kn-keyword=atypical lipomatous tumor en-keyword=CDK4 kn-keyword=CDK4 en-keyword=MDM2 kn-keyword=MDM2 en-keyword=stomach kn-keyword=stomach en-keyword=well-differentiated liposarcoma kn-keyword=well-differentiated liposarcoma END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=26752 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250723 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ADAR1 as a prognostic marker for patients with colorectal cancer and synchronous liver metastasis and a predictor of chemotherapy efficacy en-subtitle= kn-subtitle= en-abstract= kn-abstract=RNA editing by adenosine deaminase acting on RNA (ADAR) enzymes plays a role in cancer progression. However, its clinical significance in metastatic colorectal cancer (CRC) remains unclear. This study aimed to evaluate whether ADAR1 expression predicts prognosis and treatment response in colorectal cancer (CRC) with synchronous liver metastasis. This study included 40 patients with stage IV CRC and synchronous liver metastases. ADAR1 expression in tumor tissues was evaluated using immunohistochemistry. Expression levels were quantified using the immunoreactive score, and associations with clinicopathological features, overall survival (OS), and chemotherapy response were examined. High ADAR1 expression was significantly associated with multiple liver metastases (P = 0.0206), lymph node metastasis (P = 0.0241), and reduced response to chemotherapy (P = 0.0224). Significantly shorter OS was observed in patients with high ADAR1 expression in the nucleus (P = 0.0458). ADAR1 expression was an independent prognostic factor comparable to the presence of extrahepatic metastases. Low ADAR1 expression was correlated with a higher likelihood of achieving a response to chemotherapy. ADAR1 expression can reflect tumor aggressiveness and chemotherapy resistance in patients with CRC and synchronous liver metastasis. ADAR1 has considerable potential as a dual-purpose biomarker for stratifying patients based on prognosis and optimizing treatment intensity. en-copyright= kn-copyright= en-aut-name=NittaKaori en-aut-sei=Nitta en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UmedaHibiki en-aut-sei=Umeda en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriwakeKazuya en-aut-sei=Moriwake en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakedaSho en-aut-sei=Takeda en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KishimotoHiroyuki en-aut-sei=Kishimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KayanoMasashi en-aut-sei=Kayano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraShunsuke en-aut-sei=Nakamura en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KondoYuhei en-aut-sei=Kondo en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MiyakeEiki en-aut-sei=Miyake en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=17 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=24 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=25 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=RNA editing kn-keyword=RNA editing en-keyword=Liver metastasis kn-keyword=Liver metastasis en-keyword=Chemotherapy kn-keyword=Chemotherapy en-keyword=Biomarker kn-keyword=Biomarker en-keyword=Colorectal cancer kn-keyword=Colorectal cancer END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=158 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oncolytic virus-mediated p53 activation boosts the antitumor immunity of a p53-transduced dendritic cell vaccine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells (DCs) transduced with replication-deficient, wild-type human p53-expressing adenovirus Ad-p53 (Ad-p53 DCs) induce p53-targeting cytotoxic T lymphocytes (CTLs). However, the antitumor efficacy of Ad-p53 DCs is diminished by weak p53 immunogenicity in tumor cells and poor immune responses. We developed a p53-armed oncolytic adenovirus, OBP-702, to induce tumor-specific p53 expression and antitumor immune response, suggesting a role for OBP-702 in enhancing the antitumor efficacy of Ad-p53 DCs. The combined effect of Ad-p53 DCs and OBP-702 was investigated using murine colon cancer (CC) tumor models. Ad-p53 DCs were obtained by stimulating bone marrow-derived cells with granulocyte-macrophage colony-stimulating factor, interleukin-4, and Ad-p53. Subcutaneous tumor models of CT26 (p53 wild-type) and MC38 (p53 mutant-type) murine CC cell lines were used to evaluate the therapeutic potential of combination therapy in the terms of tumor growth, abscopal effect, antitumor immune response, and presentation of p53 peptides in tumor cells. Combination therapy with Ad-p53 DCs and OBP-702 significantly suppressed the growth of p53-intact CT26 tumors at treated and untreated sites by inducing tumor-infiltration of CD8+ CTLs and CD11c+ DCs. OBP-702-infected tumor cells presented human p53 epitopes in the context of major histocompatibility complex molecules, which were recognized by CTLs induced by Ad-p53 DCs. Combination therapy significantly suppressed the growth of p53-mutant MC38 tumors by activating the antitumor immune response. Our results suggest that OBP-702-mediated presentation of p53 epitopes on tumor cells enhances the antitumor efficacy of Ad-p53 DCs against murine CC tumors by attracting p53-targeting CTLs. en-copyright= kn-copyright= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuemoriKanto en-aut-sei=Suemori en-aut-mei=Kanto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkadaNaohiro en-aut-sei=Okada en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KajiwaraYoshinori en-aut-sei=Kajiwara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InoueHiroaki en-aut-sei=Inoue en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HashimotoNaoyuki en-aut-sei=Hashimoto en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Neutron Therapy Research Center, Okayama University Hospital kn-affil= affil-num=14 en-affil=Oncolys BioPharma, Inc kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=2 article-no= start-page=euaf024 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SCN5A variant type-dependent risk prediction in Brugada syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims The variant in SCN5A with the loss of function (LOF) effect in the cardiac Na+ channel (Nav1.5) is the definitive cause for Brugada syndrome (BrS), and the functional analysis data revealed that LOF variants are associated with poor prognosis. However, which variant types (e.g. missense or non-missense) affect the prognoses of those variant carriers remain unelucidated.
Methods and results We defined SCN5A LOF variants as all non-missense and missense variants that produce peak INa < 65% of wild-type previously confirmed by patch-clamp studies. The study population consisted of 76 Japanese BrS patients (74% patients were male and the median age [IQR] at diagnosis was 28 [14–45] years) with LOF type of SCN5A variants: 40 with missense and 36 with non-missense variants. Non-missense variant carriers presented significantly more severe cardiac conduction disorder compared to the missense variant carriers. During follow-up periods of 9.0 [5.0–14.0] years, compared to missense variants, non-missense variants were significant risk factors of lifetime lethal arrhythmia events (LAEs) (P = 0.023). When focusing only on the missense variants that produce no peak INa, these missense variant carriers exhibited the same clinical outcomes as those with non-missense (log-rank P = 0.325). After diagnosis, however, both variant types were comparable in risk of LAEs (P = 0.155).
Conclusion We identified, for the first time, that SCN5A non-missense variants were associated with higher probability of LAE than missense variants in BrS patients though it did not change significantly after diagnosis. en-copyright= kn-copyright= en-aut-name=AizawaTakanori en-aut-sei=Aizawa en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakiyamaTakeru en-aut-sei=Makiyama en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangHai en-aut-sei=Huang en-aut-mei=Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImamuraTomohiko en-aut-sei=Imamura en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuyamaMegumi en-aut-sei=Fukuyama en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SonodaKeiko en-aut-sei=Sonoda en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatoKoichi en-aut-sei=Kato en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraYuko en-aut-sei=Nakamura en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HoshinoKenji en-aut-sei=Hoshino en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OzawaJunichi en-aut-sei=Ozawa en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SuzukiHiroshi en-aut-sei=Suzuki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YasudaKazushi en-aut-sei=Yasuda en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AokiHisaaki en-aut-sei=Aoki en-aut-mei=Hisaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KuritaTakashi en-aut-sei=Kurita en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YoshidaYoko en-aut-sei=Yoshida en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SuzukiTsugutoshi en-aut-sei=Suzuki en-aut-mei=Tsugutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakamuraYoshihide en-aut-sei=Nakamura en-aut-mei=Yoshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OgawaYoshiharu en-aut-sei=Ogawa en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamagamiShintaro en-aut-sei=Yamagami en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FukudaMasakazu en-aut-sei=Fukuda en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OnoMakoto en-aut-sei=Ono en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KondoHidekazu en-aut-sei=Kondo en-aut-mei=Hidekazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=TakahashiNaohiko en-aut-sei=Takahashi en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=OhnoSeiko en-aut-sei=Ohno en-aut-mei=Seiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakagawaYoshihisa en-aut-sei=Nakagawa en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=OnoKoh en-aut-sei=Ono en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HorieMinoru en-aut-sei=Horie en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine , 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 , kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Medical Genome Center, National Cerebral and Cardiovascular Center kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=Department of Public Health, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Tsuchiura Kyodo General Hospital kn-affil= affil-num=10 en-affil=Department of Cardiology, Saitama Children’s Medical Center kn-affil= affil-num=11 en-affil=Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=12 en-affil=Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital kn-affil= affil-num=13 en-affil=Department of Pediatric Cardiology, Aichi Children’s Health and Medical Center kn-affil= affil-num=14 en-affil=Department of Pediatric Cardiology, Osaka Women’s and Children’s Hospital kn-affil= affil-num=15 en-affil=Division of Cardiovascular Center, Kindai University School of Medicine kn-affil= affil-num=16 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=17 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=18 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=19 en-affil=Division of Cardiology, Hyogo Prefectural Kobe Children’s Hospital kn-affil= affil-num=20 en-affil=Department of Cardiology, Tenri Hospital kn-affil= affil-num=21 en-affil=Department of Cardiovascular Therapeutics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=22 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=24 en-affil=Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=25 en-affil=Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University kn-affil= affil-num=26 en-affil=Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University kn-affil= affil-num=27 en-affil=Medical Genome Center, National Cerebral and Cardiovascular Center kn-affil= affil-num=28 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=29 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=30 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= en-keyword=Brugada syndrome kn-keyword=Brugada syndrome en-keyword=SCN5A kn-keyword=SCN5A en-keyword=Lethal arrhythmia event kn-keyword=Lethal arrhythmia event en-keyword=Variant type kn-keyword=Variant type en-keyword=Loss of function kn-keyword=Loss of function END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=2 article-no= start-page=395 end-page=412.e6 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tissue-level oscillation is achieved by tissue-intrinsic clocks along with network-dependent signals originating from distal organs and organismal behavior. Yet, it remains unexplored whether maternal circadian rhythms during pregnancy influence fetal rhythms and impact long-term susceptibility to dietary challenges in offspring. Here, we demonstrate that circadian disruption during pregnancy decreased placental and neonatal weight yet retained transcriptional and structural maturation. Intriguingly, diet-induced obesity was exacerbated in parallel with arrhythmic feeding behavior, hypothalamic leptin resistance, and hepatic circadian reprogramming in offspring of chronodisrupted mothers. In utero circadian desynchrony altered the phase-relationship between the mother and fetus and impacted placental efficiency. Temporal feeding restriction in offspring failed to fully prevent obesity, whereas the circadian alignment of caloric restriction with the onset of the active phase virtually ameliorated the phenotype. Thus, maternal circadian rhythms during pregnancy confer adaptive properties to metabolic functions in offspring and provide insights into the developmental origins of health and disease. en-copyright= kn-copyright= en-aut-name=YaoNa en-aut-sei=Yao en-aut-mei=Na kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinouchiKenichiro en-aut-sei=Kinouchi en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatohManami en-aut-sei=Katoh en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AshtianiKousha Changizi en-aut-sei=Ashtiani en-aut-mei=Kousha Changizi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbdelkarimSherif en-aut-sei=Abdelkarim en-aut-mei=Sherif kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimotoHiroyuki en-aut-sei=Morimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TorimitsuTakuto en-aut-sei=Torimitsu en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KozumaTakahide en-aut-sei=Kozuma en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwaharaAkihide en-aut-sei=Iwahara en-aut-mei=Akihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KosugiShotaro en-aut-sei=Kosugi en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KomuroJin en-aut-sei=Komuro en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KatoKyosuke en-aut-sei=Kato en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TonomuraShun en-aut-sei=Tonomura en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakamuraToshifumi en-aut-sei=Nakamura en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItohArata en-aut-sei=Itoh en-aut-mei=Arata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamaguchiShintaro en-aut-sei=Yamaguchi en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YoshinoJun en-aut-sei=Yoshino en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IrieJunichiro en-aut-sei=Irie en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HashimotoHisayuki en-aut-sei=Hashimoto en-aut-mei=Hisayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SatohAkiko en-aut-sei=Satoh en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MikamiYohei en-aut-sei=Mikami en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=UchidaShusaku en-aut-sei=Uchida en-aut-mei=Shusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=UekiTakatoshi en-aut-sei=Ueki en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NomuraSeitaro en-aut-sei=Nomura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=BaldiPierre en-aut-sei=Baldi en-aut-mei=Pierre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=HayashiKaori en-aut-sei=Hayashi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=ItohHiroshi en-aut-sei=Itoh en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Computer Science, University of California kn-affil= affil-num=5 en-affil=Department of Computer Science, University of California kn-affil= affil-num=6 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=7 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=10 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=11 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=12 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=13 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=16 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=17 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=19 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=20 en-affil=Department of Cardiovascular Medicine, Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=21 en-affil=Department of Integrative Physiology, Institute of Development, Aging and Cancer, Tohoku University kn-affil= affil-num=22 en-affil=Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=23 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=24 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=25 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=26 en-affil=Department of Computer Science, University of California kn-affil= affil-num=27 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=28 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= en-keyword=circadian rhythm kn-keyword=circadian rhythm en-keyword=metabolism kn-keyword=metabolism en-keyword=circadian clock kn-keyword=circadian clock en-keyword=pregnancy kn-keyword=pregnancy en-keyword=developmental origins of health and disease kn-keyword=developmental origins of health and disease en-keyword=obesity kn-keyword=obesity en-keyword=leptin kn-keyword=leptin en-keyword=time-restricted feeding kn-keyword=time-restricted feeding en-keyword=caloric restriction kn-keyword=caloric restriction en-keyword=eating behavior kn-keyword=eating behavior END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=3 article-no= start-page=e70085 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acute effect of multipoint pacing and fused AV delay in patients receiving cardiac resynchronization therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure with dyssynchrony. However, one-third of patients do not respond positively to it. Recently, multipoint pacing (MPP), which involves pacing from two sites on the left ventricle, has been found to improve symptoms and hemodynamics compared to conventional CRT. An automatic fused atrioventricular (AV) delay that performs fused pacing for intrinsic conduction has also been introduced. However, the combined effect of MPP and fused AV delay on acute hemodynamics is unknown.
Objective: To evaluate the acute hemodynamic effects of MPP and fused AV delay in patients undergoing CRT.
Methods: A pressure wire was delivered to the left ventricle, and dp/dt was compared with single atrial stimulation pacing in 52 patients with various pacing configurations.
Results: Delta dp/dt was greater in MPP than in conventional CRT (10.5 ± 1.0% vs. 8.2 ± 1.0%, p < 0.001) and in fused AV delay than in short AV delay (10.4 ± 0.8% vs. 8.3 ± 1.1, p < 0.001). Hemodynamic parameters significantly most improved with the combination of MPP and fused AV delay. Delta dp/dt was greater in LV pacing than in biventricular (BiV) pacing with MPP and fused AV delay; however, the delta QRS duration was shorter in LV pacing than in BiV pacing. Delta dp/dt and delta QRS duration were negatively correlated. The super-responder rate was 66%.
Conclusion: Combining MPP and fused AV delay has an additional effect. Shortening the QRS duration can increase the dp/dt, but the estimated line differs between LV and BiV pacing. en-copyright= kn-copyright= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MizunoTomofumi en-aut-sei=Mizuno en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UeokaAkira en-aut-sei=Ueoka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasudaTakuro en-aut-sei=Masuda en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaSaori en-aut-sei=Asada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawadaSatoshi en-aut-sei=Kawada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=cardiac resynchronization therapy kn-keyword=cardiac resynchronization therapy en-keyword=dp/dt kn-keyword=dp/dt en-keyword=fused AV delay kn-keyword=fused AV delay en-keyword=LV pacing kn-keyword=LV pacing en-keyword=multipoint pacing kn-keyword=multipoint pacing END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=9 article-no= start-page=1203 end-page=1205 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Technique for Implanting the Second Valve Accompanied by Simultaneous Snorkel Stenting en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TodaHironobu en-aut-sei=Toda en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UekiYuta en-aut-sei=Ueki en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraShohei en-aut-sei=Hara en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimitsuYusuke en-aut-sei=Morimitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=sinus sequestration kn-keyword=sinus sequestration en-keyword=snorkel stenting kn-keyword=snorkel stenting en-keyword=structural valve deterioration kn-keyword=structural valve deterioration en-keyword=TAVR-in-TAVR kn-keyword=TAVR-in-TAVR en-keyword=transvalvular leakage kn-keyword=transvalvular leakage END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=115 end-page=119 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Safety of Adenosine-assisted Clipping Surgery for Unruptured Cerebral Aneurysms: Interim Results of a Single-center, Single-arm Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this single-center, single-arm study was to evaluate the safety of adenosine-assisted clipping surgery for unruptured cerebral aneurysms. Five patients underwent aneurysmal clipping during adenosine-induced hypotension at ≤60 mmHg. The mean age of patients was 63.4±8.5 years, and the mean aneurysm size was 5.3±1.1 mm. The prevalence of patients with modified Rankin Scale scores of zero 30 days after surgery was 100%. The degree of aneurysm obliteration was complete in 4 patients and residual dome in 1 patient. The mean total dosage of adenosine was 37.4±18.8 mg. The mean duration of systolic blood pressure at ≤60 mmHg was 64.2±28.3 secs. No patients exhibited paroxysmal atrial fibrillation within 24 hours after adenosine administration or elevation of high-sensitivity cardiac troponin T on postoperative day 1. There was no reduction in either motor-evoked or somatosensory-evoked potential amplitude during surgery. Adenosine-induced hypotension is a safe procedure in clipping surgery for unruptured cerebral aneurysms. en-copyright= kn-copyright= en-aut-name=HISHIKAWATomohito en-aut-sei=HISHIKAWA en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MURAISatoshi en-aut-sei=MURAI en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HIRAMATSUMasafumi en-aut-sei=HIRAMATSU en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HARUMAJun en-aut-sei=HARUMA en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EBISUDANIYuki en-aut-sei=EBISUDANI en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YASUHARATakao en-aut-sei=YASUHARA en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SUGIUKenji en-aut-sei=SUGIU en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SHIMIZUKazuyoshi en-aut-sei=SHIMIZU en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NAKAGAWAKoji en-aut-sei=NAKAGAWA en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KIMURA-ONOAya en-aut-sei=KIMURA-ONO en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HOTTAKatsuyuki en-aut-sei=HOTTA en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MORIMATSUHiroshi en-aut-sei=MORIMATSU en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=DATEIsao en-aut-sei=DATE en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurosurgery, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=adenosine kn-keyword=adenosine en-keyword=clipping kn-keyword=clipping en-keyword=safety kn-keyword=safety en-keyword=unruptured cerebral aneurysm kn-keyword=unruptured cerebral aneurysm END start-ver=1.4 cd-journal=joma no-vol=965 cd-vols= no-issue=1 article-no= start-page=52 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Unraveling the Cr Isotopes of Ryugu: An Accurate Aqueous Alteration Age and the Least Thermally Processed Solar System Material en-subtitle= kn-subtitle= en-abstract= kn-abstract=The analysis of samples returned from the C-type asteroid Ryugu has drastically advanced our knowledge of the evolution of early solar system materials. However, no consensus has been obtained on the chronological data, which is important for understanding the evolution of the asteroid Ryugu. Here, the aqueous alteration age of Ryugu particles was determined by the Mn–Cr method using bulk samples, yielding an age of 4.13 + 0.62/−0.55 Myr after the formation of Ca–Al-rich inclusions (CAI). The age corresponds to 4563.17 + 0.60/−0.67 Myr ago. The higher 55Mn/52Cr, ε54Cr, and initial ε53Cr values of the Ryugu samples relative to any carbonaceous chondrite samples implies that its progenitor body formed from the least thermally processed precursors in the outermost region of the protoplanetary disk. Despite accreting at different distances from the Sun, the hydrous asteroids (Ryugu and the parent bodies of CI, CM, CR, and ungrouped C2 meteorites) underwent aqueous alteration during a period of limited duration (3.8 ± 1.8 Myr after CAI). These ages are identical to the crystallization age of the carbonaceous achondirtes NWA 6704/6693 within the error. The ε54Cr and initial ε53Cr values of Ryugu and NWA 6704/6693 are also identical, while they show distinct Δ'17O values. This suggests that the precursors that formed the progenitor bodies of Ryugu and NWA 6703/6693 were formed in close proximity and experienced a similar degree of thermal processing in the protosolar nebula. However, the progenitor body of Ryugu was formed by a higher ice/dust ratio, than NWA6703/6693, in the outer region of the protoplanetary disk. en-copyright= kn-copyright= en-aut-name=TanakaRyoji en-aut-sei=Tanaka en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RatnayakeDilan M. en-aut-sei=Ratnayake en-aut-mei=Dilan M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtaTsutomu en-aut-sei=Ota en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiklusicakNoah en-aut-sei=Miklusicak en-aut-mei=Noah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunihiroTak en-aut-sei=Kunihiro en-aut-mei=Tak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PotiszilChristian en-aut-sei=Potiszil en-aut-mei=Christian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaguchiChie en-aut-sei=Sakaguchi en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KobayashiKatsura en-aut-sei=Kobayashi en-aut-mei=Katsura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamanakaMasahiro en-aut-sei=Yamanaka en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AbeMasanao en-aut-sei=Abe en-aut-mei=Masanao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MiyazakiAkiko en-aut-sei=Miyazaki en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakatoAiko en-aut-sei=Nakato en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakazawaSatoru en-aut-sei=Nakazawa en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishimuraMasahiro en-aut-sei=Nishimura en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkadaTatsuaki en-aut-sei=Okada en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SaikiTakanao en-aut-sei=Saiki en-aut-mei=Takanao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaSatoshi en-aut-sei=Tanaka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TeruiFuyuto en-aut-sei=Terui en-aut-mei=Fuyuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TsudaYuichi en-aut-sei=Tsuda en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=UsuiTomohiro en-aut-sei=Usui en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=WatanabeSei-ichiro en-aut-sei=Watanabe en-aut-mei=Sei-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YadaToru en-aut-sei=Yada en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=YogataKasumi en-aut-sei=Yogata en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshikawaMakoto en-aut-sei=Yoshikawa en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=NakamuraEizo en-aut-sei=Nakamura en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=5 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=6 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=7 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=8 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=9 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=10 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=11 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=12 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=13 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=14 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=15 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=16 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=17 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=18 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=19 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=20 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=21 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=22 en-affil=Department of Earth and Planetary Sciences, Nagoya University kn-affil= affil-num=23 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=24 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=25 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=26 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=599 cd-vols= no-issue=13 article-no= start-page=1914 end-page=1924 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250525 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characterization of molecular mechanisms of CaMKKα/1 oligomerization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is an activating kinase for calcium/calmodulin-dependent protein kinase type 1 (CaMKI), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), RAC-alpha serine/threonine-protein kinase (PKB), and AMP-activated protein kinase (AMPK) that has been reported to form an active oligomer in cells. Glutathione S-transferase (GST) pulldown assay from the extracts of COS-7 cells expressing GST- and His6-CaMKKα/1 mutants showed that the C-terminal region containing the autoinhibitory and calmodulin (CaM)-binding sequence (residues 438–463) is required for CaMKKα/1 homo-oligomerization. This was confirmed by the fact that the GST-CaMKKα/1 C-terminal domain (residues 435–505) directly interacted with EGFP-CaMKKα/1 residues 435–505 as well as with wild-type CaMKKα/1. Notably, once oligomerized in cells, CaMKKα/1 is neither exchangeable between the oligomeric complexes nor dissociated by Ca2+/CaM binding. These results support stable oligomerization of CaMKK in the cells by intermolecular self-association of its C-terminal region containing a regulatory domain. en-copyright= kn-copyright= en-aut-name=UenoyamaShun en-aut-sei=Uenoyama en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NittaHayato en-aut-sei=Nitta en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuizuFutoshi en-aut-sei=Suizu en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokumitsuHiroshi en-aut-sei=Tokumitsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=3 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Medical Technology, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=6 en-affil= kn-affil= en-keyword=calmodulin kn-keyword=calmodulin en-keyword=calmodulin-kinase cascade kn-keyword=calmodulin-kinase cascade en-keyword=CaMKKa/ kn-keyword=CaMKKa/ en-keyword=oligomerization kn-keyword=oligomerization en-keyword=protein–protein interaction kn-keyword=protein–protein interaction en-keyword=regulatory domain kn-keyword=regulatory domain END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=26 article-no= start-page=12024 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collective motions in the primary coordination sphere: a critical functional framework for catalytic activity of the oxygen-evolving complex of photosystem II en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosynthetic water oxidation, vital for dioxygen production and light energy conversion, is catalyzed by the oxygen-evolving complex of photosystem II, where the inorganic Mn4CaO5 cluster acts as the catalytic core. In this study, we investigate the functional significance of collective motions of amino acid side chains within the primary coordination sphere of the Mn cluster, focusing on their role in modulating the energetic demands for catalytic transformations in the S3 state. We applied regularized canonical correlation analysis to quantitatively correlate the three-dimensional arrangement of coordinating atoms with catalytic driving forces computed via density functional theory. Our analysis reveals that distinct collective side chain motions profoundly influence the energetic requirements for structural reconfigurations of the Mn cluster, achieved through expansion and contraction of the ligand cavity while fine-tuning its geometry to stabilize key intermediates. Complementary predictions from a neural network-based machine learning model indicate that the coordination sphere exerts a variable energetic impact on the catalytic transformations of the Mn cluster, depending on the S-state environment. Integrated computational analyses suggest that the extended lifetime of the S3YZ˙ state, consistently observed after three flash illuminations, may result from slow, progressive protein dynamics that continuously reshape the energy landscape, thereby shifting the equilibrium positions of rapid, reversible chemical processes over time. Overall, our findings demonstrate that collective motions in the primary coordination sphere constitute an active, dynamic framework essential for the efficient execution of multi-electron catalysis under ambient conditions, while simultaneously achieving a high selectivity with irreversible nature required for effective 3O2 evolution. en-copyright= kn-copyright= en-aut-name=IsobeHiroshi en-aut-sei=Isobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiTakayoshi en-aut-sei=Suzuki en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamaguchiKizashi en-aut-sei=Yamaguchi en-aut-mei=Kizashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=5 en-affil=Center for Quantum Information and Quantum Biology, Osaka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=5 article-no= start-page=164 end-page=173 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nephronophthisis and Retinitis Pigmentosa (Senior-Loken Syndrome) After Living-Donor Kidney Transplantation: Twelve-Year Follow-Up in a Young Woman en-subtitle= kn-subtitle= en-abstract= kn-abstract=Senior-Loken syndrome is a hereditary ciliopathy with recessive trait that manifests as nephronophthisis and retinitis pigmentosa. This report described an 18-year-old woman who was referred to a University Hospital to set up a treatment plan for chronic renal failure of an unknown cause. She had experienced nocturnal polyurea from the age of 12 years and was found to have an elevated level of serum creatinine at 3 mg/dL at the age of 15 years. She underwent renal biopsy at a hometown regional hospital which showed global glomerulosclerosis in six of the 13 glomeruli examined, renal tubular dilation in irregular shape, and marked interstitial fibrosis with lymphocytic infiltration. At the age of 19 years, she received a living-donor kidney transplant from her 46-year-old father as a preemptive therapy. At surgery, biopsy of the father’s donor kidney showed two glomeruli with global sclerosis out of 24 glomeruli examined, in association with minimal interstitial fibrosis and lymphocytic infiltration. She began to have extended-release tacrolimus 4 mg daily and mycophenolate mofetil 1,000 mg daily. According to the standard protocol, she underwent biopsy of the transplanted donor kidney to reveal interstitial fibrosis and lymphocytic infiltration, in addition to no sign of rejection and no glomerular deposition of immunoglobulins and complements, both 4 weeks and 14 months after the kidney transplantation. At the age of 23 years, 4 years after the kidney transplantation, she was, for the first time, diagnosed retinitis pigmentosa, and hence, Senior-Loken syndrome. She was followed up in the stable condition with basal doses of tacrolimus 5 mg daily, mycophenolate mofetil 1,000 mg daily, and prednisolone 5 mg daily up until now in 12 years after the kidney transplantation. The interstitial fibrosis with lymphocytic infiltration in the donor kidney might be a milder presentation of the disease with recessive inheritance. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Retinitis pigmentosa kn-keyword=Retinitis pigmentosa en-keyword=Nephronophthisis kn-keyword=Nephronophthisis en-keyword=Senior-Loken syndrome kn-keyword=Senior-Loken syndrome en-keyword=Kidney transplantation kn-keyword=Kidney transplantation en-keyword=Living donor kn-keyword=Living donor en-keyword=Kidney biopsy kn-keyword=Kidney biopsy en-keyword=Pathology kn-keyword=Pathology en-keyword=Computed tomography scan kn-keyword=Computed tomography scan en-keyword=Ciliopathy kn-keyword=Ciliopathy en-keyword=Optical coherence tomography kn-keyword=Optical coherence tomography END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=745 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250521 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploring the relationship between posture-dependent airway assessment in orthodontics: insights from kinetic MRI, cephalometric data, and three-dimensional MRI analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Previous studies have assessed the upper airway using various examination methods, such as cephalometric imaging and magnetic resonance imaging (MRI). However, there is a significant gap in the research regarding the relationship between these different imaging modalities. This study compares airway assessments using kinetic MRI and cephalometric scans, examining their correlation with three dimensional (3D) MRI data.
Materials and methods Kinetic MRI, cephalometric scans, and 3D MRI of forty-seven participants were used in the present study. Airway areas and widths were measured at the retropalatal, retroglossal, and hypopharyngeal levels in both kinetic MRI and cephalometric scans. Airway volumes were calculated from 3D MRI data. Statistical analyses, including the Wilcoxon Signed Rank test, Spearman correlation, and multiple linear regression, were performed to evaluate the data and identify significant differences, correlations, and prediction models, respectively.
Results Significant differences were found between kinetic MRI and cephalometric scans. Cephalometric data showed larger airway areas and widths compared to kinetic MRI measurements. Although both cephalometric and kinetic MRI showed a correlation with 3D MRI, kinetic MRI demonstrated stronger correlations with 3D MRI airway volumes than cephalometric scans. According to our linear regression model equations, RPA-Max (maximum retropalatal airway area) and RPA (retropalatal airway area) can elucidate variations in RPV (retropalatal airway volume). RGA-Med (median retroglossal airway area) and RGA-Min (minimum retroglossal airway area) can explain variations in RGV (retroglossal airway volume). HPA (hypopharyngeal airway area) and ULHPAW-Max (maximum upper limit hypopharyngeal airway width) account for variations in HPV (hypopharyngeal airway volume). Additionally, TA-Max (maximum total airway area) can account for variations in TPV (total pharyngeal airway volume).ConclusionBoth cephalometric data and kinetic MRI data showed correlations with 3D MRI data. The shared posture of kinetic MRI and 3D MRI led to stronger correlations between these two modalities. Although cephalometric data had fewer correlations with 3D MRI and predictors for 3D airway volume, they were still significant. Our study highlights the complementary nature of kinetic MRI and cephalometric imaging, as both provide valuable information for airway assessment and exhibit significant correlations with 3D MRI data. en-copyright= kn-copyright= en-aut-name=OkaNaoki en-aut-sei=Oka en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HabumugishaJanvier en-aut-sei=Habumugisha en-aut-mei=Janvier kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraMasahiro en-aut-sei=Nakamura en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KataokaTomoki en-aut-sei=Kataoka en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujisawaAtsuro en-aut-sei=Fujisawa en-aut-mei=Atsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawanabeNoriaki en-aut-sei=Kawanabe en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IzawaTakashi en-aut-sei=Izawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Oral and Maxillofacial Surgery, Tottori University kn-affil= affil-num=5 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Kinetic MRI kn-keyword=Kinetic MRI en-keyword=Posture kn-keyword=Posture en-keyword=Airway assessment kn-keyword=Airway assessment END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=6 article-no= start-page=97 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of aged garlic extract on experimental periodontitis in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aged garlic extract (AGE) has been reported to exert anti‑inflammatory effects. AGE has been recently found to reduce the inflammatory symptoms of periodontitis, a widespread chronic inflammatory disease caused by oral bacterial infection. However, the mechanisms underlying these effects remain unclear. In the present study, it was aimed to determine the effects of AGE on experimental periodontitis and the related inflammatory factors. AGE (2 g/kg/day) was orally administered to 15 mice during the experimental period, while a control group consisted of 15 mice that received pure water. A total of 3 days after initiation of administration, the left maxillary second molar was ligated with a 5‑0 silk thread for 7 days. Blood biochemical tests were performed to monitor the systemic effects of AGE. Alveolar bone loss was measured morphometrically using a stereomicroscope, and reverse transcription‑quantitative PCR was performed to assay mRNAs of proinflammatory cytokines in gingival tissues. A histological survey was also performed to identify osteoclasts in periodontitis lesions (five mice per group). The total protein and albumin levels showed no significant differences between the AGE and control groups. However, ligation‑induced bone resorption was lower in the AGE group than in the control group (P=0.01). Additionally, ligature increased the mRNA expression of inflammatory cytokines, whereas AGE administration tended to suppress them. Remarkably, tumor necrosis factor gene expression was significantly suppressed (P=0.04). The number of osteoclasts in periodontitis lesions was reduced in the AGE‑treated group. These results indicate that AGE prevents alveolar bone loss by suppressing the inflammatory responses related to osteoclast differentiation in the periodontal tissue. Further research is needed to elucidate the role of AGE in reducing inflammatory bone resorption. en-copyright= kn-copyright= en-aut-name=KuangCanyan en-aut-sei=Kuang en-aut-mei=Canyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraiAnna en-aut-sei=Hirai en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Kamei‑ΝagataChiaki en-aut-sei=Kamei‑Νagata en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NangoHiroshi en-aut-sei=Nango en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtaniMasahiro en-aut-sei=Ohtani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pathophysiology‑Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Central Research Institute, Wakunaga Pharmaceutical Co., Ltd. kn-affil= affil-num=5 en-affil=Central Research Institute, Wakunaga Pharmaceutical Co., Ltd. kn-affil= affil-num=6 en-affil=Department of Pathophysiology‑Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathophysiology‑Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=AGE kn-keyword=AGE en-keyword=experimental periodontitis kn-keyword=experimental periodontitis en-keyword=bone resorption kn-keyword=bone resorption en-keyword=inflammation kn-keyword=inflammation en-keyword=osteoclasts kn-keyword=osteoclasts END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=7 article-no= start-page=193 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Osteosarcoma cell-derived CCL2 facilitates lung metastasis via accumulation of tumor-associated macrophages en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteosarcoma (OS) is the most common malignant tumor of bone in children and adolescents. Although lung metastasis is a major obstacle to improving the prognosis of OS patients, the underlying mechanism of lung metastasis of OS is poorly understood. Tumor-associated macrophages (TAMs) with M2-like characteristics are reportedly associated with lung metastasis and poor prognosis in OS patients. In this study, we investigated the metastasis-associated tumor microenvironment (TME) in orthotopic OS tumor models with non-metastatic and metastatic OS cells. Non-metastatic and metastatic tumor cells derived from mouse OS (Dunn and LM8) and human OS (HOS and 143B) were used to analyze the TME associated with lung metastasis in orthotopic OS tumor models. OS cell-derived secretion factors were identified by cytokine array and enzyme-linked immunosorbent assay (ELISA). Orthotopic tumor models with metastatic LM8 and 143B cells were analyzed to evaluate the therapeutic potential of a neutralizing antibody in the development of primary and metastatic tumors. Metastatic OS cells developed metastatic tumors with infiltration of M2-like TAMs in the lungs. Cytokine array and ELISA demonstrated that metastatic mouse and human OS cells commonly secreted CCL2, which was partially encapsulated in extracellular vesicles. In vivo experiments demonstrated that while primary tumor growth was unaffected, administration of CCL2-neutralizing antibody led to a significant suppression of lung metastasis and infiltration of M2-like TAMs in the lung tissue. Our results suggest that CCL2 plays a crucial role in promoting the lung metastasis of OS cells via accumulation of M2-like TAMs. en-copyright= kn-copyright= en-aut-name=KondoHiroya en-aut-sei=Kondo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KureMiho en-aut-sei=Kure en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DemiyaKoji en-aut-sei=Demiya en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HataToshiaki en-aut-sei=Hata en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshiokaYusuke en-aut-sei=Yoshioka en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Molecular and Cellular Medicine, Tokyo Medical University kn-affil= affil-num=14 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Osteosarcoma kn-keyword=Osteosarcoma en-keyword=Lung metastasis kn-keyword=Lung metastasis en-keyword=Tumor-associated macrophage kn-keyword=Tumor-associated macrophage en-keyword=CCL2 kn-keyword=CCL2 en-keyword=Extracellular vesicle kn-keyword=Extracellular vesicle END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=7 article-no= start-page=192 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Recent studies have revealed that CD8+ T cells can be activated via genetic upregulation of HIF-1 alpha, thereby augmenting antitumor effector functions. HIF-1 alpha upregulation can be attained by inhibiting HIF-prolyl hydroxylase (HIF-PH) under normoxic conditions, termed pseudohypoxia. This study investigated whether pseudohypoxia induced by HIF-PH inhibitors suppresses Microsatellite stable (MSS) colorectal cancer (CRC) by affecting tumor immune response.
Methods The HIF-PH inhibitors Roxadustat and Vadadustat were utilized in this study. In vitro, we assessed the effects of HIF-PH inhibitors on human and murine colon cancer cell lines (SW480, HT29, Colon26) and murine T cells. In vivo experiments were performed with mice bearing Colon26 tumors to evaluate the effect of these inhibitors on tumor immune responses. Tumor and spleen samples were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry to elucidate potential mechanisms.
Results HIF-PH inhibitors demonstrated antitumor effects in vivo but not in vitro. These inhibitors enhanced the tumor immune response by increasing the infiltration of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs). HIF-PH inhibitors induced IL-2 production in splenic and intratumoral CD4+ T cells, promoting T cell proliferation, differentiation, and immune responses. Roxadustat synergistically enhanced the efficacy of anti-PD-1 antibody for MSS cancer by increasing the recruitment of TILs and augmenting effector-like CD8+ T cells.
Conclusion Pseudohypoxia induced by HIF-PH inhibitors activates antitumor immune responses, at least in part, through the induction of IL-2 secretion from CD4+ T cells in the spleen and tumor microenvironment, thereby enhancing immune efficacy against MSS CRC. en-copyright= kn-copyright= en-aut-name=ChenYuehua en-aut-sei=Chen en-aut-mei=Yuehua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaYusuke en-aut-sei=Hamada en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangYuze en-aut-sei=Wang en-aut-mei=Yuze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TianMiao en-aut-sei=Tian en-aut-mei=Miao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Colorectal cancer kn-keyword=Colorectal cancer en-keyword=Microsatellite stable kn-keyword=Microsatellite stable en-keyword=Hypoxia-inducible factor kn-keyword=Hypoxia-inducible factor en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=1 article-no= start-page=1 end-page=15 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Improved sedimentary layer model including the accretionary prism in the fore-arc region of the Ryukyu arc, Japan kn-title=南西諸島の前弧域における付加体を含む堆積層のモデル化 en-subtitle= kn-subtitle= en-abstract= kn-abstract=　We combine the recent seismic reflection profiles to construct a new seismic velocity model of the sedimentary layer incorporating the accretionary prism along the Ryukyu trench. In constructing the new model, we refer to the zoning (ZONE1 to ZONE4) identified by Okamura et al. (2017, Tectonophys.). The construction process consists of the following steps: First, we digitize either unconformities or VP=4 to 5 km/s lines as the seismic basement, whichever is more clearly identifiable. Second, the digitized thickness data of the sedimentary layer from the reflection profiles are geometrically modeled and interpolated to make the three-dimensional structure model. Finally, we supplement the external region of the constructed 3-D sedimentary model using the J-SHIS model provided by the NIED to complete the velocity structure model in the entire Ryukyu arc. The main features of our model are as follows: In ZONE1, off Ishigaki-jima island, the thick sedimentary layer extends about 50 km wide from the Ryukyu trench. In ZONE2, off Miyako-jima island, the thinner layer compared to the other zones is found near the trench, with a thin sedimentary terrace covering the area behind it. In ZONE3, off Okinawa-jima island, the sedimentary layer deepens as it approaches the trench. In ZONE4, off Tokara islands, the deepest layer among all zones is identified. We then conduct 3-D finite-difference simulations of seismic wave propagation using the new and the previous models to confirm the improvement of the new model. In the simulations, the effects of the accretionary prism along the Ryukyu trench on the seismic wave propagation are clearly identified. en-copyright= kn-copyright= en-aut-name=KOMATSUMasanao en-aut-sei=KOMATSU en-aut-mei=Masanao kn-aut-name=小松正直 kn-aut-sei=小松 kn-aut-mei=正直 aut-affil-num=1 ORCID= en-aut-name=URAKAMISohei en-aut-sei=URAKAMI en-aut-mei=Sohei kn-aut-name=浦上想平 kn-aut-sei=浦上 kn-aut-mei=想平 aut-affil-num=2 ORCID= en-aut-name=OKAMOTOTaro en-aut-sei=OKAMOTO en-aut-mei=Taro kn-aut-name=岡元太郎 kn-aut-sei=岡元 kn-aut-mei=太郎 aut-affil-num=3 ORCID= en-aut-name=TAKENAKAHiroshi en-aut-sei=TAKENAKA en-aut-mei=Hiroshi kn-aut-name=竹中博士 kn-aut-sei=竹中 kn-aut-mei=博士 aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama Gakuin University kn-affil=岡山学院大学 affil-num=2 en-affil=Formerly Department of Earth Sciences, Okayama University kn-affil=元・岡山大学大学院自然科学研究科 affil-num=3 en-affil=Department of Earth and Planetary Sciences, School of Science, Institute of Science Tokyo kn-affil=東京科学大学理学院地球惑星科学系 affil-num=4 en-affil=Department of Earth Sciences, Okayama University kn-affil=岡山大学学術研究院環境生命自然科学学域 en-keyword=Sedimentary layer model kn-keyword=Sedimentary layer model en-keyword=Accretionary prism kn-keyword=Accretionary prism en-keyword=Ryukyu arc kn-keyword=Ryukyu arc END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=36 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anticoagulant effects of edoxaban in cancer and noncancer patients with venous thromboembolism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Edoxaban, a direct oral anticoagulant (DOAC), is a first-line treatment for venous thromboembolism (VTE) and the suppression of VTE recurrence. In patients with cancer, however, recurrent VTE after DOAC treatment may be more common than in noncancer patients. To evaluate our hypothesis that the anticoagulation effect of edoxaban is lower in VTE patients with cancer than in noncancer patients.
Methods This study was a prospective, multicenter, observational study including patients treated with edoxaban for VTE in Japan. The primary outcome was the difference in the prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer level at 5 h after initial edoxaban administration between the cancer and noncancer groups. An additional outcome was the longitudinal change in PT and APTT from 5 h to overnight after edoxaban administration. The incidence of adverse events was further investigated.
Results PT and APTT at 5 h after initial edoxaban administration were not significantly different between the cancer (n = 84) and noncancer groups (n = 138) (e.g., log-transformed APTT 3.55 vs. 3.55, p = 0.45). However, D-dimer in the cancer groups was significantly greater than that in the noncancer groups (log-transformed 1.83 vs. 1.79, p = 0.009). PT and APTT significantly decreased from 5 h to overnight after edoxaban, but a similar pattern was observed in each group. All adverse events after edoxaban administration were also similar between patients with cancer and noncancer.
Conclusion PT and APTT after edoxaban administration were similar between VTE patients with cancer and noncancer groups, suggesting that edoxaban has anticoagulation effects on cancer-associated VTE similar to those of noncancer patients.
Trial registration UMIN000041973; Registration Date: 2020.10.5. en-copyright= kn-copyright= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuoNaoaki en-aut-sei=Matsuo en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaitoTakanori en-aut-sei=Naito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurodaKazuhiro en-aut-sei=Kuroda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokiokaKoji en-aut-sei=Tokioka en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HatanakaKunihiko en-aut-sei=Hatanaka en-aut-mei=Kunihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujimotoRyohei en-aut-sei=Fujimoto en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamaokaHidenaru en-aut-sei=Yamaoka en-aut-mei=Hidenaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KajikawaYutaka en-aut-sei=Kajikawa en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SurugaKazuki en-aut-sei=Suruga en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SugiyamaHiroki en-aut-sei=Sugiyama en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiyajiTsuyoshi en-aut-sei=Miyaji en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MorimotoYoshimasa en-aut-sei=Morimoto en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OkamuraNobuhiro en-aut-sei=Okamura en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SarashinaToshihiro en-aut-sei=Sarashina en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama City Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama Rosai Hospital kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, NHO Fukuyama Medical Center kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Okayama Medical Center kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=13 en-affil=Hosogi Hospital kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=15 en-affil=Okamura Isshindow Hospital kn-affil= affil-num=16 en-affil=Kuroda Clinic kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School kn-affil= affil-num=21 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Factor Xa inhibitors kn-keyword=Factor Xa inhibitors en-keyword=Anticoagulation effects kn-keyword=Anticoagulation effects en-keyword=Cancer kn-keyword=Cancer en-keyword=Venous thromboembolism kn-keyword=Venous thromboembolism END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=116 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Colorectal cancer (CRC) is considered the third most common type of cancer worldwide. Tumor-associated macrophages (TAMs) have been shown to promote drug resistance. Adenosine-to-inosine RNA-editing, as regulated by adenosine deaminase acting on RNA (ADAR), is a process that induces the posttranscriptional modification of critical oncogenes. The aim of this study is to determine whether the signals from cancer cells would induce RNA-editing in macrophages.
Methods The effects of RNA-editing on phenotypes in macrophages were analyzed using clinical samples and in vitro and in vivo models.
Results The intensity of the RNA-editing enzyme ADAR1 (Adenosine deaminase acting on RNA 1) in cancer and mononuclear cells indicated a strong positive correlation between the nucleus and cytoplasm. The ADAR1-positive mononuclear cells were positive for CD68 and CD163, a marker for M2 macrophages. Cancer cells transport pro-inflammatory cytokines or ADAR1 protein directly to macrophages via the exosomes, promoting RNA-editing in AZIN1 (Antizyme Inhibitor 1) and GLI1 (Glioma-Associated Oncogene Homolog 1) and resulting in M2 macrophage polarization. GLI1 RNA-editing in the macrophages induced by cancer cells promotes the secretion of SPP1, which is supplied to the cancer cells. This activates the NF kappa B pathway in cancer cells, promoting oxaliplatin resistance. When the JAK inhibitors were administered, oncogenic RNA-editing in the macrophages was suppressed. This altered the macrophage polarization from M2 to M1 and decreased oxaliplatin resistance in cancer cells.
Conclusions This study revealed that ADAR1-high TAMs are crucial in regulating drug resistance in CRC and that targeting ADAR1 in TAMs could be a promising treatment approach for overcoming drug resistance in CRC. en-copyright= kn-copyright= en-aut-name=UmedaHibiki en-aut-sei=Umeda en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriwakeKazuya en-aut-sei=Moriwake en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakedaSho en-aut-sei=Takeda en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KishimotoHiroyuki en-aut-sei=Kishimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KayanoMasashi en-aut-sei=Kayano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MoriYoshiko en-aut-sei=Mori en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=GoelAjay en-aut-sei=Goel en-aut-mei=Ajay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=17 en-affil=Department of Obstetrics and Gynecology, Okayama University Gradu�ate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Comprehensive Cancer Center kn-affil= affil-num=24 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=RNA-editing kn-keyword=RNA-editing en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Chemoresistance kn-keyword=Chemoresistance en-keyword=Biomarker kn-keyword=Biomarker en-keyword=Colorectal cancer kn-keyword=Colorectal cancer END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=101 end-page=107 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effectiveness of Postoperative Irradiation in Patients with cN0 Early Breast Cancer Treated with Sentinel Lymph Node Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=To evaluate the effectiveness of postoperative irradiation (POI) for patients with cN0 early breast cancer, we retrospectively analyzed the cases of 650 consecutive breast cancer patients who underwent sentinel lymph node (SLN)-guided surgery (2005-2022) at our hospital. In this cohort, 53% (278/521) of the patients who underwent breast conservative surgery (BCS) and 96% (124/129) of those treated with mastectomy did not receive POI. The patients who underwent BCS were treated with POI using opposing tangential field irradiation. A false negative (FN) SLN was retrospectively defined as a negative metastasis in SLN plus positive recurrence in the axillary lymph nodes. Recurrence was detected in 83 patients. A logistic regression analysis revealed that the nuclear grade (odds ratio [OR] 1.69), POI (OR 0.41), and postoperative hormone therapy (OR 0.40) were each significantly related to recurrence. The 26.1% (12/46) FN rate of the non-POI patients decreased to 5.8% (1/17) compared to those treated with POI. The rate of axillary recurrence was significantly lower in the POI group (0.4%) versus the non-POI group (2.7%) (p=0.0355). The rate of locoregional recurrence was also significantly lower in the POI group (2.0%) versus the non-POI group (13.4%) (p<0.0001). No significant difference was observed in the rate of distant recurrence between the POI (4.0%) and non-POI (3.3%) (p=0.831) groups. These results indicated that the postoperative opposing tangential field irradiation of conserved breast tissue inhibited recurrence in the axillary lymph nodes. en-copyright= kn-copyright= en-aut-name=IsozakiHiroshi en-aut-sei=Isozaki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoSasau en-aut-sei=Matsumoto en-aut-mei=Sasau kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakamaTakehiro en-aut-sei=Takama en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IsozakiYuka en-aut-sei=Isozaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Oomoto Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Oomoto Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=postoperative irradiation kn-keyword=postoperative irradiation en-keyword=radiation therapy kn-keyword=radiation therapy en-keyword=sentinel lymph nodes kn-keyword=sentinel lymph nodes en-keyword=recurrence kn-keyword=recurrence END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=6 article-no= start-page=2485 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vesicular Glutamate Transporter 3 Is Involved in Glutamatergic Signalling in Podocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glomerular podocytes act as a part of the filtration barrier in the kidney. The activity of this filter is regulated by ionotropic and metabotropic glutamate receptors. Adjacent podocytes can potentially release glutamate into the intercellular space; however, little is known about how podocytes release glutamate. Here, we demonstrated vesicular glutamate transporter 3 (VGLUT3)-dependent glutamate release from podocytes. Immunofluorescence analysis revealed that rat glomerular podocytes and an immortal mouse podocyte cell line (MPC) express VGLUT1 and VGLUT3. Consistent with this finding, quantitative RT-PCR revealed the expression of VGLUT1 and VGLUT3 mRNA in undifferentiated and differentiated MPCs. In addition, the exocytotic proteins vesicle-associated membrane protein 2, synapsin 1, and synaptophysin 1 were present in punctate patterns and colocalized with VGLUT3 in MPCs. Interestingly, approximately 30% of VGLUT3 colocalized with VGLUT1. By immunoelectron microscopy, VGLUT3 was often observed around clear vesicle-like structures in differentiated MPCs. Differentiated MPCs released glutamate following depolarization with high potassium levels and after stimulation with the muscarinic agonist pilocarpine. The depletion of VGLUT3 in MPCs by RNA interference reduced depolarization-dependent glutamate release. These results strongly suggest that VGLUT3 is involved in glutamatergic signalling in podocytes and may be a new drug target for various kidney diseases. en-copyright= kn-copyright= en-aut-name=NishiiNaoko en-aut-sei=Nishii en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiTomoko en-aut-sei=Kawai en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuokaHiroki en-aut-sei=Yasuoka en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeTadashi en-aut-sei=Abe en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TatsumiNanami en-aut-sei=Tatsumi en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaradaYuika en-aut-sei=Harada en-aut-mei=Yuika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyajiTakaaki en-aut-sei=Miyaji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LiShunai en-aut-sei=Li en-aut-mei=Shunai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsukanoMoemi en-aut-sei=Tsukano en-aut-mei=Moemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OgawaDaisuke en-aut-sei=Ogawa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakeiKohji en-aut-sei=Takei en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cell Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University kn-affil= affil-num=7 en-affil=Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University kn-affil= affil-num=8 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Central Research Laboratory, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=VGLUT3 kn-keyword=VGLUT3 en-keyword=glutamate kn-keyword=glutamate en-keyword=podocyte kn-keyword=podocyte en-keyword=glutamatergic transmission kn-keyword=glutamatergic transmission END start-ver=1.4 cd-journal=joma no-vol=301 cd-vols= no-issue=4 article-no= start-page=108334 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of basic amino acid residues in substrate binding and transport of the light-driven anion pump Synechocystis halorhodopsin (SyHR) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Microbial rhodopsins are photoreceptive seventransmembrane a-helical proteins, many of which function as ion transporters, primarily for small monovalent ions such as Na+, K+, Cl-, Br-, and I-. Synechocystis halorhodopsin (SyHR), identified from the cyanobacterium Synechocystis sp. PCC 7509, uniquely transports the polyatomic divalent SO42- inward, in addition to monovalent anions (Cl- and Br-). In this study, we conducted alanine-scanning mutagenesis on twelve basic amino acid residues to investigate the anion transport mechanism of SyHR. We quantitatively evaluated the Cl-and SO42- transport activities of the WT SyHR and its mutants. The results showed a strong correlation between the Cl-and SO42- transport activities among them (R = 0.94), suggesting a shared pathway for both anions. Notably, the R71A mutation selectively abolished SO42- transport activity while maintaining Cl- transport, whereas the H167A mutation significantly impaired both Cl-and SO42- transport. Furthermore, spectroscopic analysis revealed that the R71A mutant lost its ability to bind SO42- due to the absence of a positive charge, while the H167A mutant failed to accumulate the O intermediate during the photoreaction cycle (photocycle) due to reduced hydrophilicity. Additionally, computational analysis revealed the SO42- binding modes and clarified the roles of residues involved in its binding around the retinal chromophore. Based on these findings and previous structural information, we propose that the positive charge and hydrophilicity of Arg71 and His167 are crucial for the formation of the characteristic initial and transient anion-binding site of SyHR, enabling its unique ability to bind and transport both Cl-and SO42-. en-copyright= kn-copyright= en-aut-name=NakamaMasaki en-aut-sei=Nakama en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NojiTomoyasu en-aut-sei=Noji en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshizawaSusumu en-aut-sei=Yoshizawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshikitaHiroshi en-aut-sei=Ishikita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=microbial rhodopsin kn-keyword=microbial rhodopsin en-keyword=anion transport kn-keyword=anion transport en-keyword=retinal kn-keyword=retinal en-keyword=membrane protein kn-keyword=membrane protein en-keyword=photobiology kn-keyword=photobiology END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=3 article-no= start-page=32 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rapid development of naked malting barley germplasm through targeted mutagenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Covered barley (Hordeum vulgare) has historically been preferred for malting, as the husk in this plant protects the embryo during harvest and acts as a filter during brewing. Naked barley, which is typically used as food, has the potential to be used in brewing due to recent technical advances, but the grains contain higher levels of β-glucan and polyphenols, which are undesirable in brewing. Introducing the naked trait into brewing cultivars through crossing is time-consuming due to the need to eliminate these undesirable traits. In this study, we rapidly developed naked barley that is potentially suitable for malting by introducing targeted mutations into Nudum (NUD) using CRISPR/Cas9-mediated targeted mutagenesis. The doubled haploid line ‘DH120366’, which was used as the parental line, was derived from a cross between two covered malting barley cultivars. We generated CRISPR/Cas9-mediated targeted mutagenized barley harboring mutations in NUD via Agrobacterium tumefaciens-mediated transformation and confirmed the presence of mosaic mutations in one individual from among 16 T0 transformants. We sowed T1 grains exhibiting the naked trait and sequenced the NUD gene in these T1 seedlings, identifying two types of mutations. Shotgun high-throughput whole-genome sequencing confirmed the absence of the transgene in at least one nud mutant line following k-mer-based analysis. Cultivation in a closed growth chamber revealed no significant differences in agronomic traits between the nud mutants and the wild type. This study demonstrates the feasibility of rapidly developing naked barley with potential use for malting and brewing by targeting only NUD via targeted mutagenesis. en-copyright= kn-copyright= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakaiHiroaki en-aut-sei=Sakai en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamaokaMika en-aut-sei=Hamaoka en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MunemoriHiromi en-aut-sei=Munemori en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbeFumitaka en-aut-sei=Abe en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MeintsBrigid en-aut-sei=Meints en-aut-mei=Brigid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HayesPatrick M. en-aut-sei=Hayes en-aut-mei=Patrick M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Research Center for Advanced Analysis, National Agriculture and Food Research Organization kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Institute of Crop Science, National Agriculture and Food Research Organization kn-affil= affil-num=6 en-affil=Department Crop and Soil Science, Oregon State University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=8 en-affil=Department Crop and Soil Science, Oregon State University kn-affil= en-keyword=Hordeum vulgare kn-keyword=Hordeum vulgare en-keyword=Covered (hulled) kn-keyword=Covered (hulled) en-keyword=Naked (hull-less) kn-keyword=Naked (hull-less) en-keyword=Genome editing kn-keyword=Genome editing en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=Transformation amenability kn-keyword=Transformation amenability END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=235 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distinct Infection Mechanisms of Rhizoctonia solani AG-1 IA and AG-4 HG-I+II in Brachypodium distachyon and Barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rhizoctonia solani is a basidiomycete phytopathogenic fungus that causes rapid necrosis in a wide range of crop species, leading to substantial agricultural losses worldwide. The species complex is divided into 13 anastomosis groups (AGs) based on hyphal fusion compatibility and further subdivided by culture morphology. While R. solani classifications were shown to be independent of host specificity, it remains unclear whether different R. solani isolates share similar virulence mechanisms. Here, we investigated the infectivity of Japanese R. solani isolates on Brachypodium distachyon and barley. Two isolates, AG-1 IA (from rice) and AG-4 HG-I+II (from cauliflower), infected leaves of both plants, but only AG-4 HG-I+II infected roots. B. distachyon accessions Bd3-1 and Gaz-4 and barley cultivar 'Morex' exhibited enhanced resistance to both isolates compared to B. distachyon Bd21 and barley cultivars 'Haruna Nijo' and 'Golden Promise'. During AG-1 IA infection, but not AG-4 HG-I+II infection, resistant Bd3-1 and Morex induced genes for salicylic acid (SA) and N-hydroxypipecolic acid (NHP) biosynthesis. Pretreatment with SA or NHP conferred resistance to AG-1 IA, but not AG-4 HG-I+II, in susceptible B. distachyon Bd21 and barley Haruna Nijo. On the leaves of susceptible Bd21 and Haruna Nijo, AG-1 IA developed extensive mycelial networks with numerous infection cushions, which are specialized infection structures well-characterized in rice sheath blight. In contrast, AG-4 HG-I+II formed dispersed mycelial masses associated with underlying necrosis. We propose that the R. solani species complex encompasses at least two distinct infection strategies: AG-1 IA exhibits a hemibiotrophic lifestyle, while AG-4 HG-I+II follows a predominantly necrotrophic strategy. en-copyright= kn-copyright= en-aut-name=MahadevanNiranjan en-aut-sei=Mahadevan en-aut-mei=Niranjan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FernandaRozi en-aut-sei=Fernanda en-aut-mei=Rozi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KouzaiYusuke en-aut-sei=Kouzai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KohnoNatsuka en-aut-sei=Kohno en-aut-mei=Natsuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaoReiko en-aut-sei=Nagao en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NyeinKhin Thida en-aut-sei=Nyein en-aut-mei=Khin Thida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeMegumi en-aut-sei=Watanabe en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakataNanami en-aut-sei=Sakata en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MochidaKeiichi en-aut-sei=Mochida en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NoutoshiYoshiteru en-aut-sei=Noutoshi en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Crop Stress Management Group, Division of Plant Molecular Regulation Research, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO) kn-affil= affil-num=4 en-affil=Faculty of Agriculture, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Agriculture, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=12 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=13 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=14 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Rhizoctonia solani species complex kn-keyword=Rhizoctonia solani species complex en-keyword=virulence mechanism kn-keyword=virulence mechanism en-keyword=infection behavior kn-keyword=infection behavior en-keyword=salicylic acid kn-keyword=salicylic acid en-keyword=N-hydroxypipecolic acid kn-keyword=N-hydroxypipecolic acid END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=3 article-no= start-page=96 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer-associated fibroblasts promote pro-tumor functions of neutrophils in pancreatic cancer via IL-8: potential suppression by pirfenidone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The mechanisms by which neutrophils acquire pro-tumor properties remain poorly understood. In pancreatic cancer, cancer-associated fibroblasts (CAFs) may interact with neutrophils, directing them to promote tumor progression.
Methods To validate the association between CAFs and neutrophils, the localization of neutrophils was examined in clinically resected pancreatic cancer specimens. CAFs were produced by culturing in cancer-conditioned media, and the effects of these CAFs on neutrophils were examined. In vitro migration and invasion assays assess the effect of CAF-activated neutrophils on cancer cells. The factors secreted by the activated neutrophils were also explored. Finally, pirfenidone (PFD) was tested to determine whether it could suppress the pro-tumor functions of activated neutrophils.
Results In pancreatic cancer specimens, neutrophils tended to co-localize with IL-6-positive CAFs. Neutrophils co-cultured with CAFs increased migratory capacity and prolonged life span. CAF-affected neutrophils enhance the migratory and invasive activities of pancreatic cancer cells. IL-8 is the most upregulated cytokine secreted by the neutrophils. PFD suppresses IL-8 secretion from CAF-stimulated neutrophils and mitigates the malignant traits of pancreatic cancer cells.
Conclusion CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach. en-copyright= kn-copyright= en-aut-name=YagiTomohiko en-aut-sei=Yagi en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NogiShohei en-aut-sei=Nogi en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniguchiAtsuki en-aut-sei=Taniguchi en-aut-mei=Atsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimotoMasashi en-aut-sei=Yoshimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuemoriKanto en-aut-sei=Suemori en-aut-mei=Kanto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujitaShuto en-aut-sei=Fujita en-aut-mei=Shuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Neutrophil kn-keyword=Neutrophil en-keyword=Anti-fibrotic agent kn-keyword=Anti-fibrotic agent en-keyword=Pirfenidone kn-keyword=Pirfenidone END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Wake Not a Sleeping Lion: Free Trade Agreements and Decision Rights in Multinationals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Free trade agreements with rules of origin affect the location of input production for vertically integrated multinational enterprises. The relocation induced by a free trade agreement changes the allocation of decision rights within multinational enterprises and the purpose of transfer pricing from avoiding high taxes to strengthening their product market competitiveness. This study shows that a free trade agreement with rules of origin may hurt both a multinational enterprise and a local firm, despite tariff elimination, when the relocation occurs and the decision rights change from centralization to decentralization. Moreover, such a free trade agreement can hurt consumers. Nevertheless, rules of origin increase the feasibility of free trade agreements due to larger tax revenues. en-copyright= kn-copyright= en-aut-name=MukunokiHiroshi en-aut-sei=Mukunoki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkoshiHirofumi en-aut-sei=Okoshi en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Economics, Gakushuin University kn-affil= affil-num=2 en-affil=Faculty of Economics, Okayama University kn-affil= en-keyword=free trade agreements kn-keyword=free trade agreements en-keyword=managerial incentives kn-keyword=managerial incentives en-keyword=rules of origin kn-keyword=rules of origin en-keyword=transfer pricing kn-keyword=transfer pricing END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=3267 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and alpha-smooth muscle (alpha-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro. Anti-tumor effects of anti-IL-6R Ab on PM of GC were investigated in an orthotopic murine PM model. IL-6 expression was significantly correlated with alpha-SMA expression in clinical samples of GC, and higher IL-6 expression in the primary tumor was associated with poor prognosis of GC. Higher IL-6 and alpha-SMA expressions were also observed in PM of GC. In vitro, differentiation of fibroblasts into CAFs and chemoresistance were observed in GC cells cocultured with fibroblasts. Anti-IL-6R Ab inhibited the progression of PM in GC cells cocultured with fibroblasts in the orthotopic mouse model but could not inhibit the progression of PM consisting of GC cells alone. IL-6 expression in the TME was associated with poor prognosis of GC, and CAFs were associated with establishment and progression of PM via IL-6. Anti-IL-6R Ab could inhibit PM of GC by the blockade of IL-6 secreted by CAFs, which suggests its therapeutic potential for PM of GC. en-copyright= kn-copyright= en-aut-name=MitsuiEma en-aut-sei=Mitsui en-aut-mei=Ema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkuraTomohiro en-aut-sei=Okura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UneYuta en-aut-sei=Une en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhtsukaJunko en-aut-sei=Ohtsuka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhkiRieko en-aut-sei=Ohki en-aut-mei=Rieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=12 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Peritoneal metastasis kn-keyword=Peritoneal metastasis en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=Interleukin-6 kn-keyword=Interleukin-6 en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Interleukin-6 receptor antibody kn-keyword=Interleukin-6 receptor antibody END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=コダマカワザンショウ属の八重山諸島産新種 (腹足綱: クビキレガイ上科: カワザンショウ科) — 同属で世界最北の現生種 kn-title=A new species of Ovassiminea Thiele, 1927 (Gastropoda: Truncatelloidea: Assimineidae) from the Yaeyama Islands, Okinawa, southern Japan — the northernmost record among recent species of the genus en-subtitle= kn-subtitle= en-abstract=沖縄県八重山諸島の西表島・石垣島から新種 Ovassiminea hayasei n. sp. ウラウチコダマカワザンショウを記載する。Ovassiminea Thiele, 1927 コダマカワザンショウ属は西太平洋の熱帯・亜熱帯に分布し, 本新種は同属中で世界最北の現生種である。本新種の産地は極端に狭い範囲に限られ, 沖縄県と環境省のレッドリストで絶滅危惧II類 (VU) とされている。なお文末の Appendix には, これまでに記載されたコダマカワザンショウ属全種 (現生5・化石5) の目録を, 異名表とともに挙げる。 kn-abstract=Ovassiminea hayasei n. sp. is described from mangrove swamps in Iriomote and Ishigaki Islands, of the Yaeyama Islands at the southwestern part of the Ryūkyū Archipelago, Okinawa, Japan. This is the northernmost record among recent species of the genus Ovassiminea Thiele, 1927, which is distributed in the tropical and subtropical regions of the Western Pacific. The new species is known to be restricted to extremely narrow ranges and is evaluated as vulnerable in red lists by the governments of Japan and Okinawa Prefecture. A list of all available (five recent and five fossil) species names of Ovassiminea hitherto described, with synonymies, is also given as an Appendix. en-copyright= kn-copyright= en-aut-name=FukudaHiroshi en-aut-sei=Fukuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuboHirofumi en-aut-sei=Kubo en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Conservation of Aquatic Biodiversity, Faculty of Agriculture, Okayama University kn-affil= affil-num=2 en-affil=Okinawa Prefectural Institute of Health and Environment kn-affil= en-keyword=anatomy kn-keyword=anatomy en-keyword=conservation kn-keyword=conservation en-keyword=description kn-keyword=description en-keyword=endangered species kn-keyword=endangered species en-keyword=estuary kn-keyword=estuary en-keyword=Iriomote Island kn-keyword=Iriomote Island en-keyword=Ishigaki Island kn-keyword=Ishigaki Island en-keyword=mangrove swamp kn-keyword=mangrove swamp en-keyword=salt marsh kn-keyword=salt marsh en-keyword=taxonomy kn-keyword=taxonomy END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=74 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Case series showing the safety and changes in lipid profiles of hemodialysis patients with hypertriglyceridemia after pemafibrate administration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Cardiovascular disease is a major cause of morbidity and mortality in patients with chronic kidney disease and end-stage renal disease (ESRD). Dyslipidemia is a key focus of cardiovascular therapy and is characterized by hypertriglyceridemia mainly caused by lipoprotein lipase-mediated metabolism of ApoC-III in patients with ESRD. Pemafbrate, a selective peroxisome proliferator-activated receptor alpha modulator, can be used regardless of renal function and inhibit ApoC-III expression in the liver.
Case presentation We reported the cases of four patients on hemodialysis who met at least 175 mg/dL of triglycerides on the consecutive three tests between September 2022 and November 2022 and took 0.1 mg pemafbrate twice a day from November 2022 to May 2023. They experienced no adverse events after pemafbrate treatment. Pemafbrate signifcantly reduced triglyceride (TG) (302±72 to 140±50 mg/dL, p=0.048), total cholesterol (187±34 to 156±48 mg/dL, p=0.025), and Apo C-III (15.9±8.2 to 12.6±7.1, p=0.030) levels. Apo A-II levels signifcantly increased after treatment (27.0±6.1 to 37.1±5.8, p=0.041).
Conclusions Pemafbrate decreased TG, total cholesterol, and Apo-CIII and increased Apo A-II without adverse events. Further study is needed to examine the favorable efects of pemafbrate on the risk of CVD. en-copyright= kn-copyright= en-aut-name=OkadaRino en-aut-sei=Okada en-aut-mei=Rino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiNaoya en-aut-sei=Kobayashi en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiharaHiroyuki en-aut-sei=Ishihara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YokoyamaTomohisa en-aut-sei=Yokoyama en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MifuneTomoyo en-aut-sei=Mifune en-aut-mei=Tomoyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakurabuYoshimasa en-aut-sei=Sakurabu en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NojimaIchiro en-aut-sei=Nojima en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=4 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=5 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=6 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Hemodialysis kn-keyword=Hemodialysis en-keyword=Dyslipidemia kn-keyword=Dyslipidemia en-keyword=Apolipoprotein kn-keyword=Apolipoprotein en-keyword=Pemafibrate kn-keyword=Pemafibrate END start-ver=1.4 cd-journal=joma no-vol=391 cd-vols= no-issue= article-no= start-page=158 end-page=176 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Magnesium isotope composition of volcanic rocks from cold and warm subduction zones: Implications for the recycling of subducted serpentinites and carbonates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Magnesium (Mg) isotopes are regarded as a sensitive tracer to the contribution from subducted serpentinites and carbonates. However, the source, distribution, and controlling factors of the Mg isotope composition of arc magmas remain unclear. In this study, we investigated the intra-arc and inter-arc variations in Mg isotope compositions of volcanic rocks from two typical cold subduction zones [NE Japan (NEJ) and Izu arcs] and a typical hot subduction zone [SW Japan (SWJ) arc] to address the question. The volcanic rocks from the frontal-arc regions of NEJ and Izu have isotopically heavy Mg (δ26Mg = –0.20 to –0.08 ‰) compared to the mantle-like δ26Mg values of most of volcanic rocks from SWJ and the rear regions of NEJ and Izu arcs (–0.28 to –0.17 ‰). It is also worth noting that NEJ arc includes samples with δ26Mg values (–0.61 to –0.39 ‰) significantly lower than the mantle, but similar to the < 110 Ma intra-continental basalts from eastern China, which is the first observation in modern arc rocks. No obvious effects of post-eruptive alteration, fractional crystallization, partial melting, or the addition of silicate-rich sediment and oceanic crust components could be identified in the Mg isotope compositions of these volcanic rocks. By contrast, the correlations between the δ26Mg values and the proxy for serpentinite component (i.e., 11B/10B and Nb/B ratios) indicate that the component exerts a strong control on the Mg-isotopic signature of these arc rocks. Considering metamorphic reactions in subduction lithologies under P-T conditions postulated for these arcs, the variations in δ26Mg values of these arc magmas are unlikely to have been controlled by dehydration of serpentinites in subducted oceanic lithosphere (slab serpentinite). Instead, the high-δ26Mg values of frontal-arc rocks are delivered by the fluids from serpentinite formed in the lowermost part of the sub-arc mantle (mantle wedge serpentinite) in channelized flow. Comparatively, such a high-δ26Mg signature is invisible in volcanic rocks from rear-arc regions of NEJ and Izu, and the entire SWJ, suggesting that the major Mg carriers in subducted serpentinites (e.g., talc, chlorite, and serpentine) were broken down completely before subducted slabs reached the depth beneath these volcanoes. Moreover, the volcanic rocks with low δ26Mg values from the rear arc of NEJ are characterized by high La/Yb and U/Nb ratios as well as low Ti/Eu, Ti/Ti*, and Hf/Hf* ratios, suggesting the involvements of carbonates in their magma sources. The quantitative modeling suggests that < 20 % of sedimentary carbonate (dolomite) was recycled into their mantle source, revealing that Mg-rich carbonate could be incorporated into a deep mantle wedge at rear-arc depths of 150–400 km in subduction zones. en-copyright= kn-copyright= en-aut-name=ZhangWei en-aut-sei=Zhang en-aut-mei=Wei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangFang en-aut-sei=Huang en-aut-mei=Fang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=CAS Key Laboratory of Crust-Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= en-keyword=Magnesium isotopes kn-keyword=Magnesium isotopes en-keyword=Arc magmas kn-keyword=Arc magmas en-keyword=Mantle wedge serpentinite kn-keyword=Mantle wedge serpentinite en-keyword=Slab serpentinite kn-keyword=Slab serpentinite en-keyword=Carbonate recycle kn-keyword=Carbonate recycle END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue= article-no= start-page=274 end-page=280 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=About Dr. Kubota Jiro who lived in Kaminishigawa, Okayama City, and his son, Tsutomu kn-title=上西川町の窪田次郎、そして勤のこと en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YAMASHITAHiroshi en-aut-sei=YAMASHITA en-aut-mei=Hiroshi kn-aut-name=山下洋 kn-aut-sei=山下 kn-aut-mei=洋 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue= article-no= start-page=15 end-page=26 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Development Status of Research on Maintenance and Continuation of Festival Events and Folk Performing Arts: An Attempt at Quantitative Understanding kn-title=祭礼行事・民俗芸能の維持・存続に関する研究の展開状況─その数量的把握の試み─ en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TAKANOHiroshi en-aut-sei=TAKANO en-aut-mei=Hiroshi kn-aut-name=髙野宏 kn-aut-sei=髙野 kn-aut-mei=宏 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=187 cd-vols= no-issue= article-no= start-page=145 end-page=151 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=What Is “Meaning” ? kn-title=意味づけするとは何か en-subtitle= kn-subtitle= en-abstract= kn-abstract=　人間はコミュニケーションの動物であると言われる。しかしその対象についての解釈（意味）が異なればコミュニケーションは成立しない。本論では意味づけするとはどういうことなのかについて考える。 en-copyright= kn-copyright= en-aut-name=MIYAZAKIHiroshi en-aut-sei=MIYAZAKI en-aut-mei=Hiroshi kn-aut-name=宮﨑宏志 kn-aut-sei=宮﨑 kn-aut-mei=宏志 aut-affil-num=1 ORCID= en-aut-name=SOBUKAWATakuya en-aut-sei=SOBUKAWA en-aut-mei=Takuya kn-aut-name=曽布川拓也 kn-aut-sei=曽布川 kn-aut-mei=拓也 aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Education, Okayama University kn-affil=岡山大学学術研究院教育学域 affil-num=2 en-affil=Global Education Center, Waseda University kn-affil=早稲田大学グローバルエデュケーションセンター en-keyword=素象 kn-keyword=素象 en-keyword=コミュニケーション kn-keyword=コミュニケーション en-keyword=意味づけ kn-keyword=意味づけ END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=50 article-no= start-page=50041 end-page=50048 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Conformational Flexibility of D1-Glu189: A Crucial Determinant in Substrate Water Selection, Positioning, and Stabilization within the Oxygen-Evolving Complex of Photosystem II en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosynthetic water oxidation is a vital process responsible for producing dioxygen and supplying the energy necessary to sustain life on Earth. This fundamental reaction is catalyzed by the oxygen-evolving complex (OEC) of photosystem II, which houses the Mn4CaO5 cluster as its catalytic core. In this study, we specifically focus on the D1-Glu189 amino acid residue, which serves as a direct ligand to the Mn4CaO5 cluster. Our primary goal is to explore, using density functional theory (DFT), how the conformational flexibility of the D1-Glu189 side chain influences crucial catalytic processes, particularly the selection, positioning, and stabilization of a substrate water molecule within the OEC. Our investigation is based on a hypothesis put forth by Li et al. (Nature, 2024, 626, 670), which suggests that during the transition from the S2 to S3 state, a specific water molecule temporarily coordinating with the Ca ion, referred to as O6*, may exist as a hydroxide ion (OH-). Our results demonstrate a key mechanism by which the detachment of the D1-Glu189 carboxylate group from its coordination with the Ca ion allows the creation of a specialized microenvironment within the OEC that enables the selective attraction of O6* in its deprotonated form (OH-) and stabilizes it at the catalytic metal (MnD) site. Our findings indicate that D1-Glu189 is not only a structural ligand for the Ca ion but may also play an active and dynamic role in the catalytic process, positioning O6* optimally for its subsequent participation in the oxidation sequence during the water-splitting cycle. en-copyright= kn-copyright= en-aut-name=IsobeHiroshi en-aut-sei=Isobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiTakayoshi en-aut-sei=Suzuki en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamaguchiKizashi en-aut-sei=Yamaguchi en-aut-mei=Kizashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=5 en-affil=Center for Quantum Information and Quantum Biology, Osaka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=小児心臓手術における人工心肺中のカルボキシヘモグロビンおよびメトヘモグロビンと溶血の関係性 kn-title=Carboxyhemoglobin and Methemoglobin Levels and Hemolysis in Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YOSHIDATsubasa en-aut-sei=YOSHIDA en-aut-mei=Tsubasa kn-aut-name=吉田翼 kn-aut-sei=吉田 kn-aut-mei=翼 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=患者腫瘍移植モデルに対するヒト化抗Fibroblast Atcivation Protein抗体を用い癌関連線維芽細胞を標的とした光免疫療法 kn-title=Near-infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Patient-Derived Xenografts Using a Humanized Anti-Fibroblast Activation Protein Antibody en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KOBAYASHITeruki en-aut-sei=KOBAYASHI en-aut-mei=Teruki kn-aut-name=小林照貴 kn-aut-sei=小林 kn-aut-mei=照貴 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=22 article-no= start-page=11942 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distribution and Incorporation of Extracellular Vesicles into Chondrocytes and Synoviocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteoarthritis (OA) is a chronic disease affecting over 500 million people worldwide. As the population ages and obesity rates rise, the societal burden of OA is increasing. Pro-inflammatory cytokines, particularly interleukin-1β, are implicated in the pathogenesis of OA. Recent studies suggest that crosstalk between cartilage and synovium contributes to OA development, but the mechanisms remain unclear. Extracellular vesicles (EVs) were purified from cell culture-conditioned medium via ultracentrifugation and confirmed using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. We demonstrated that EVs were taken up by human synoviocytes and chondrocytes in vitro, while in vivo experiments revealed that fluorescent-labelled EVs injected into mouse joints were incorporated into chondrocytes and synoviocytes. EV uptake was significantly inhibited by dynamin-mediated endocytosis inhibitors, indicating that endocytosis plays a major role in this process. Additionally, co-culture experiments with HEK-293 cells expressing red fluorescent protein (RFP)-tagged CD9 and the chondrocytic cell line OUMS-27 confirmed the transfer of RFP-positive EVs across a 600-nm but not a 30-nm filter. These findings suggest that EVs from chondrocytes are released into joint fluid and taken up by cells within the cartilage, potentially facilitating communication between cartilage and synovium. The results underscore the importance of EVs in OA pathophysiology. en-copyright= kn-copyright= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoIkumi en-aut-sei=Sato en-aut-mei=Ikumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakashitaRen en-aut-sei=Takashita en-aut-mei=Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KodamaShintaro en-aut-sei=Kodama en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkemuraKentaro en-aut-sei=Ikemura en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OpokuGabriel en-aut-sei=Opoku en-aut-mei=Gabriel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeShogo en-aut-sei=Watanabe en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FurumatsuTakayuki en-aut-sei=Furumatsu en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AndoMitsuru en-aut-sei=Ando en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AkiyoshiKazunari en-aut-sei=Akiyoshi en-aut-mei=Kazunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Neuroscience, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Laboratory of Biomaterials, Institute for Life and Medical Sciences, Kyoto University kn-affil= affil-num=11 en-affil=Department of Immunology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=extracellular vesicles (EVs) kn-keyword=extracellular vesicles (EVs) en-keyword=chondrocytes kn-keyword=chondrocytes en-keyword=synoviocytes kn-keyword=synoviocytes en-keyword=osteoarthritis (OA) kn-keyword=osteoarthritis (OA) END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=1 article-no= start-page=139 end-page=146 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=2023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tooth morphology fusion technique is more accurate than conventional technique in transferring morphology of provisional to definitive screw-retained, implant-supported crown: A preliminary intervention study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To compare the accuracy of the tooth morphology fusion (TMF) digital technique and customized impression transfer coping (conventional) technique when transferring the morphology of a provisional crown to a definitive screw-retained implant-supported crown.
Methods: Six cases of partial edentulism (one anterior and five posterior) treated with oral implant placement in our clinic for the loss of three or fewer teeth in the maxilla or mandible between April 2017 and September 2018 were included. After implant placement and re-entry surgery, provisional restorations were made and adjusted to obtain the ideal morphology. Two definitive restorations were constructed by transferring the complete morphology of the provisional restorations, including the subgingival contour, using the TMF digital and conventional techniques. Three sets of surface morphological data were obtained using a desktop scanner. The three-dimensional total discrepancy volume (TDV) between the provisional restoration (reference) and the two definitive restorations was digitally measured by overlapping the surface data of the stone cast using the Boolean operation. Each TDV ratio (%) was calculated by dividing the TDV by the volume of provisional restoration. The median TDV ratios for TMF and conventional techniques were compared using the Wilcoxon signed-rank test.
Results: The median TDV ratio between provisional and definitive restorations constructed using the TMF digital technique (8.05%) was significantly lower than that obtained using the conventional technique (13.56%, P < 0.05).
Conclusions: In this preliminary intervention study, the TMF digital technique was more accurate than the conventional technique for the transfer of morphology from provisional to definitive prosthesis. en-copyright= kn-copyright= en-aut-name=MinoTakuya en-aut-sei=Mino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurosakiYoko en-aut-sei=Kurosaki en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokumotoKana en-aut-sei=Tokumoto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IzumiKoji en-aut-sei=Izumi en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsumuneHiroshi en-aut-sei=Mitsumune en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaekawaKenji en-aut-sei=Maekawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UedaAkihiro en-aut-sei=Ueda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoTomohito en-aut-sei=Nakano en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SejimaJunichi en-aut-sei=Sejima en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Kimura-OnoAya en-aut-sei=Kimura-Ono en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral Rehabilitation and Implantology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=SHIKEN Corporation kn-affil= affil-num=5 en-affil=SHIKEN Corporation kn-affil= affil-num=6 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Dental Technician Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Dental Technician Laboratory, Okayama University Hospital kn-affil= affil-num=9 en-affil=Dental Technician Laboratory, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Oral Rehabilitation and Implantology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Computer-aided design kn-keyword=Computer-aided design en-keyword=Dental implants kn-keyword=Dental implants en-keyword=Superstructure kn-keyword=Superstructure en-keyword=Provisional restoration kn-keyword=Provisional restoration en-keyword=Digital workflow kn-keyword=Digital workflow END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=10 article-no= start-page=e0309622 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The protective effect of carbamazepine on acute lung injury induced by hemorrhagic shock and resuscitation in rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hemorrhagic shock and resuscitation (HSR) enhances the risk of acute lung injury (ALI). This study investigated the protective effect of carbamazepine (CBZ) on HSR-induced ALI in rats. Male Sprague-Dawley rats were allocated into five distinct groups through randomization: control (SHAM), saline + HSR (HSR), CBZ + HSR (CBZ/HSR), dimethyl sulfoxide (DMSO) + HSR (DMSO/HSR), and CBZ + chloroquine (CQ) + HSR (CBZ/CQ/HSR). Subsequently, HSR models were established. To detect tissue damage, we measured lung histological changes, lung injury scores, and wet/dry weight ratios. We measured neutrophil counts as well as assessed the expression of inflammatory factors using RT-PCR to determine the inflammatory response. We detected autophagy-related proteins LC3II/LC3I, P62, Beclin-1, and Atg12-Atg5 using western blotting. Pretreatment with CBZ improved histopathological changes in the lungs and reduced lung injury scores. The CBZ pretreatment group exhibited significantly reduced lung wet/dry weight ratio, neutrophil aggregation and number, and inflammation factor (TNF-alpha and iNOS) expression. CBZ changed the expression levels of autophagy-related proteins (LC3II/LC3I, beclin-1, Atg12-Atg5, and P62), suggesting autophagy activation. However, after injecting CQ, an autophagy inhibitor, the beneficial effects of CBZ were reversed. Taken together, CBZ pretreatment improved HSR-induced ALI by suppressing inflammation, at least in part, through activating autophagy. Thus, our study offers a novel perspective for treating HSR-induced ALI. en-copyright= kn-copyright= en-aut-name=LiYaqiang en-aut-sei=Li en-aut-mei=Yaqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimizuHiroko en-aut-sei=Shimizu en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraRyu en-aut-sei=Nakamura en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LuYifu en-aut-sei=Lu en-aut-mei=Yifu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoRisa en-aut-sei=Sakamoto en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriEmiko en-aut-sei=Omori en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiToru en-aut-sei=Takahashi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=198 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical practice pattern of Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus: a cross-sectional study from lupus registry of nationwide institutions (LUNA) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis.
Methods This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage.
Results Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 <= PSL < 7.5 mg, 5.2 for 7.5 <= PSL < 10 mg, 9.0 for 10 <= PSL < 20 mg, and 43.1 for PSL >= 20 mg, using PSL < 5 mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11 mg/day and immunosuppressant use were key determinants of PCP prophylaxis.
Conclusion This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use. en-copyright= kn-copyright= en-aut-name=OnishiTakahisa en-aut-sei=Onishi en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SadaKen-Ei en-aut-sei=Sada en-aut-mei=Ken-Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HayashiKeigo en-aut-sei=Hayashi en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimiRyusuke en-aut-sei=Yoshimi en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimojimaYasuhiro en-aut-sei=Shimojima en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhnoShigeru en-aut-sei=Ohno en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KajiyamaHiroshi en-aut-sei=Kajiyama en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IchinoseKunihiro en-aut-sei=Ichinose en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoShuzo en-aut-sei=Sato en-aut-mei=Shuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraMichio en-aut-sei=Fujiwara en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YajimaNobuyuki en-aut-sei=Yajima en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KidaTakashi en-aut-sei=Kida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsuoYusuke en-aut-sei=Matsuo en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishimuraKeisuke en-aut-sei=Nishimura en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamaneTakashi en-aut-sei=Yamane en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Rheumatology, Kakogawa Central City Hospital kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine kn-affil= affil-num=7 en-affil=Center for Rheumatic Diseases, Yokohama City University Medical Center kn-affil= affil-num=8 en-affil=Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University kn-affil= affil-num=9 en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=10 en-affil=Department of Rheumatology, Fukushima Medical University School of Medicine kn-affil= affil-num=11 en-affil=Department of Rheumatology, Yokohama Rosai Hospital kn-affil= affil-num=12 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=13 en-affil=Infammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=14 en-affil=Department of Rheumatology, Tokyo Kyosai Hospital kn-affil= affil-num=15 en-affil=Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Rheumatology, Kakogawa Central City Hospital kn-affil= en-keyword=Systemic lupus erythematosus kn-keyword=Systemic lupus erythematosus en-keyword=Pneumocystis jirovecii pneumonia kn-keyword=Pneumocystis jirovecii pneumonia en-keyword=Glucocorticoid kn-keyword=Glucocorticoid en-keyword=Immunosuppressant kn-keyword=Immunosuppressant en-keyword=Practice pattern kn-keyword=Practice pattern END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1 article-no= start-page=12 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dendritic cell maturation is induced by p53-armed oncolytic adenovirus via tumor-derived exosomes enhancing systemic antitumor immunity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells (DCs) are crucial in cancer immunity, because they activate cytotoxic T cells by presenting tumor antigens. Recently, oncolytic virus therapy has been recognized as a systemic immune stimulator. We previously developed a telomerase-specific oncolytic adenovirus (OBP-301) and a p53-armed OBP-301 (OBP-702), demonstrating that these viruses strongly activate systemic antitumor immunity. However, their effects on DCs remained unclear. In the present study, the aim was to elucidate the mechanisms of DC activation by OBP-702, focusing particularly on tumor-derived exosomes. Exosomes (Exo53, Exo301, or Exo702) were isolated from conditioned media of human or murine pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and PAN02) after treatment with Ad-p53, OBP-301, or OBP-702. Exo702 derived from Panc-1 and MiaPaCa-2 cells significantly upregulated CD86, CD80, CD83 (markers of DC maturation), and IFN-γ in DCs in vitro. Similarly, Exo702 derived from PAN02 cells upregulated CD86 and IFN-γ in bone marrow-derived DCs in a bilateral PAN02 subcutaneous tumor model. This DC maturation was inhibited by GW4869, an inhibitor of exosome release, and anti-CD63, an antibody targeting the exosome marker. Intratumoral injection of OBP-702 into PAN02 subcutaneous tumors significantly increased the presence of mature DCs and CD8-positive T cells in draining lymph nodes, leading to long-lasting antitumor effects through the durable activation of systemic antitumor immunity. In conclusion, tumor-derived exosomes play a significant role in DC maturation following OBP-702 treatment and are critical for the systemic activation of antitumor immunity, leading to the abscopal effect. en-copyright= kn-copyright= en-aut-name=OhtaniTomoko en-aut-sei=Ohtani en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KumonKento en-aut-sei=Kumon en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YagiChiaki en-aut-sei=Yagi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugimotoRyoma en-aut-sei=Sugimoto en-aut-mei=Ryoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Oncolys BioPharma, Inc kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Oncolytic adenovirus kn-keyword=Oncolytic adenovirus en-keyword=p53 kn-keyword=p53 en-keyword=Dendritic cells kn-keyword=Dendritic cells en-keyword=Anti-tumor immunity kn-keyword=Anti-tumor immunity en-keyword=Exosome kn-keyword=Exosome END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=16 article-no= start-page=1373 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240817 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Direct Binding of Synaptopodin 2-Like Protein to Alpha-Actinin Contributes to Actin Bundle Formation in Cardiomyocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused a bundling of the actin filaments in the absence of alpha-actinin and enhanced the alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La fixed the movements of the two proteins on the actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance. en-copyright= kn-copyright= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OsakaHirona en-aut-sei=Osaka en-aut-mei=Hirona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TatsumiNanami en-aut-sei=Tatsumi en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArakiMiu en-aut-sei=Araki en-aut-mei=Miu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbeTadashi en-aut-sei=Abe en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KaiharaKeiko en-aut-sei=Kaihara en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakashimaEizo en-aut-sei=Takashima en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchihashiTakayuki en-aut-sei=Uchihashi en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakeiKohji en-aut-sei=Takei en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=3 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Malaria Research, Proteo-Science Center, Ehime University kn-affil= affil-num=9 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=SYNPO2L kn-keyword=SYNPO2L en-keyword=actinin kn-keyword=actinin en-keyword=actin kn-keyword=actin en-keyword=sarcomere kn-keyword=sarcomere en-keyword=cardiomyocyte kn-keyword=cardiomyocyte END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=9 article-no= start-page=212 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240831 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mutations in starch BRANCHING ENZYME 2a suppress the traits caused by the loss of ISOAMYLASE1 in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=The genetic interactions among starch biosynthesis genes can be exploited to alter starch properties, but they remain poorly understood due to the various combinations of mutations to be tested. Here, we isolated two novel barley mutants defective in starch BRANCHING ENZYME 2a (hvbe2a-1 and hvbe2a-2) based on the starch granule (SG) morphology. Both hvbe2a mutants showed elongated SGs in the endosperm and increased resistant starch content. hvbe2a-1 had a base change in HvBE2a gene, substituting the amino acid essential for its enzyme activity, while hvbe2a-2 is completely missing HvBE2a due to a chromosomal deletion. Further genetic crosses with barley isoamylase1 mutants (hvisa1) revealed that both hvbe2a mutations could suppress defects in endosperm caused by hvisa1, such as reduction in starch, increase in phytoglycogen, and changes in the glucan chain length distribution. Remarkably, hvbe2a mutations also transformed the endosperm SG morphology from the compound SG caused by hvisa1 to bimodal simple SGs, resembling that of wild-type barley. The suppressive impact was in competition with floury endosperm 6 mutation (hvflo6), which could enhance the phenotype of hvisa1 in the endosperm. In contrast, the compound SG formation induced by the hvflo6 hvisa1 mutation in pollen was not suppressed by hvbe2a mutations. Our findings provide new insights into genetic interactions in the starch biosynthetic pathway, demonstrating how specific genetic alterations can influence starch properties and SG morphology, with potential applications in cereal breeding for desired starch properties. en-copyright= kn-copyright= en-aut-name=MatsushimaRyo en-aut-sei=Matsushima en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimJune-Sik en-aut-sei=Kim en-aut-mei=June-Sik kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=McNellyRose en-aut-sei=McNelly en-aut-mei=Rose kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OitomeNaoko F. en-aut-sei=Oitome en-aut-mei=Naoko F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SeungDavid en-aut-sei=Seung en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujitaNaoko en-aut-sei=Fujita en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=John Innes Centre, Norwich Research Park kn-affil= affil-num=5 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=6 en-affil=John Innes Centre, Norwich Research Park kn-affil= affil-num=7 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=8 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=4 article-no= start-page=337 end-page=343 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pneumocephalus with Inverted Papilloma in the Frontoethmoidal Sinus: Case Report and Literature Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Here, we describe the unique case of a pneumocephalus originating from an inverted papilloma (IP) in the frontoethmoidal sinus. A 71-year-old man with diabetes presented with headaches and altered consciousness. Imaging revealed the pneumocephalus together with bone destruction in the left frontal sinus. He underwent simultaneous endoscopic endonasal and transcranial surgery using an ORBEYE exoscope. Pathological diagnosis of the tumor confirmed IP. Post-surgery, the pneumocephalus was significantly resolved and the squamous cell carcinoma antigen level, which had been elevated, decreased. This case underscores the importance of a multidisciplinary approach and innovative surgical methods in treating complex sinonasal pathologies. en-copyright= kn-copyright= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UraguchiKensuke en-aut-sei=Uraguchi en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnoSawako en-aut-sei=Ono en-aut-mei=Sawako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimizuAiko en-aut-sei=Shimizu en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkemachiRyosuke en-aut-sei=Ikemachi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkazakiYosuke en-aut-sei=Okazaki en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtaTomoyuki en-aut-sei=Ota en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumotoHiroshi en-aut-sei=Matsumoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyamotoShotaro en-aut-sei=Miyamoto en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsumuraMunechika en-aut-sei=Tsumura en-aut-mei=Munechika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashiSeiya en-aut-sei=Hayashi en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UmakoshiMichiari en-aut-sei=Umakoshi en-aut-mei=Michiari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HirashitaKoji en-aut-sei=Hirashita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital kn-affil= affil-num=11 en-affil=Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital kn-affil= affil-num=12 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=13 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=14 en-affil=Department of Neurosurgery, Kagawa Rosai Hospital kn-affil= affil-num=15 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=pneumocephalus kn-keyword=pneumocephalus en-keyword=inverted papilloma kn-keyword=inverted papilloma en-keyword=frontoethmoidal sinus kn-keyword=frontoethmoidal sinus en-keyword=endoscopic endonasal and transcranial surgery kn-keyword=endoscopic endonasal and transcranial surgery END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=4 article-no= start-page=323 end-page=330 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Recipient Age on Perioperative Complications after Pediatric Liver Transplantation: A Single-Center Retrospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=It has not been clear how recipient age affects the incidence of serious complications after pediatric living donor liver transplantation (LDLT). We investigated the records of 42 pediatric patients receiving LDLT, dividing our sample into two groups: the infant group (aged < 1 year) and the non-infant group (aged ≥ 1 year and ≤15 years). The primary outcome was postoperative complications assessed using the Clavien-Dindo classification. Multivariate analysis using the Cox regression model was applied to adjust for confounding factors in assessing the incidence of Clavien-Dindo grade ≥ III (C-D ≥ III) complications. The incidence of C-D ≥ III complications was higher in the non-infant group (46.2%) than in the infant group (12.5%) (odds ratio 6.00, 95% confidence interval [CI] 1.13-31.88, p=0.03). In multivariate analysis using the Cox regression model, the Graft-to-Recipient Weight Ratio (GRWR) was independently associated with the incidence of C-D ≥ III complications (hazard ratio [HR] 0.62, 95%CI 0.40-0.95, p=0.03), but being an infant was not (HR 0.84, 95%CI 0.35-1.98, p=0.68). In conclusion, the incidence of C-D ≥ III complications was higher in the non-infant group than in the infant group, but this was largely a function of GRWR: multivariate analysis revealed that GRWR was independently associated with complications. en-copyright= kn-copyright= en-aut-name=KatayamaAkira en-aut-sei=Katayama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraSatoshi en-aut-sei=Kimura en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsusakiTakashi en-aut-sei=Matsusaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesia, Kyoto University Hospital kn-affil= affil-num=3 en-affil=Department of Anesthesiology, Mie University Hospital kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=pediatric liver transplantation kn-keyword=pediatric liver transplantation en-keyword=postoperative severe complications kn-keyword=postoperative severe complications en-keyword=Graft-to-Recipient Weight Ratio kn-keyword=Graft-to-Recipient Weight Ratio END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=15 article-no= start-page=4384 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240726 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Serum Indoxyl Sulfate on One-Year Adverse Events in Chronic Kidney Disease Patients with Heart Failure en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. Methods and Results: This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m2 or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, p = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Conclusions: Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events. en-copyright= kn-copyright= en-aut-name=IwasakiKeiichiro en-aut-sei=Iwasaki en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UrabeChikara en-aut-sei=Urabe en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakuragiSatoru en-aut-sei=Sakuragi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiYusuke en-aut-sei=Kawai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukeSoichiro en-aut-sei=Fuke en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoiMasayuki en-aut-sei=Doi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaishiAtsushi en-aut-sei=Takaishi en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkaTakefumi en-aut-sei=Oka en-aut-mei=Takefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TokunagaNaoto en-aut-sei=Tokunaga en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Iwakuni Clinical Center kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama City Hospital kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=7 en-affil=Department of Cardiology, Kagawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Department of Cardiology, Mitoyo General Hospital kn-affil= affil-num=9 en-affil=Department of Cardiology, Tsuyama Chuo Hospital kn-affil= affil-num=10 en-affil=Department of Cardiology, Ibara City Hospital kn-affil= affil-num=11 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School kn-affil= en-keyword=heart failure kn-keyword=heart failure en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=indoxyl sulfate kn-keyword=indoxyl sulfate END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=10 article-no= start-page=1594 end-page=1601 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240713 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Re-administration of platinum-based chemotherapy for recurrent endometrial cancer: an ancillary analysis of the SGSG-012/GOTIC-004/Intergroup study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background We previously demonstrated the applicability of the concept of “platinum sensitivity” in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study.
Methods Among the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data.
Results In 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: < 12 months, 14/48 (29%); 12–23 months, 18/43 (42%); 24–35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: < 12 months, 3/48 (6%); 12–23 months, 0/19 (0%); 24–35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)].
Conclusions Re-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering. en-copyright= kn-copyright= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishioShin en-aut-sei=Nishio en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeharaKazuhiro en-aut-sei=Takehara en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoShinya en-aut-sei=Sato en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatohToyomi en-aut-sei=Satoh en-aut-mei=Toyomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimadaMuneaki en-aut-sei=Shimada en-aut-mei=Muneaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamaguchiSatoshi en-aut-sei=Yamaguchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanabeHiroshi en-aut-sei=Tanabe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakanoMasashi en-aut-sei=Takano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HorieKouji en-aut-sei=Horie en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakeiYuji en-aut-sei=Takei en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ImaiYuichi en-aut-sei=Imai en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HibinoYumi en-aut-sei=Hibino en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakekumaMunetaka en-aut-sei=Takekuma en-aut-mei=Munetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakamuraKazuto en-aut-sei=Nakamura en-aut-mei=Kazuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakanoHirokuni en-aut-sei=Takano en-aut-mei=Hirokuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraKeiichi en-aut-sei=Fujiwara en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Kurume University School of Medicine kn-affil= affil-num=3 en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Tottori University kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba kn-affil= affil-num=6 en-affil=Department of Gynecology, Tohoku University Hospital kn-affil= affil-num=7 en-affil=Department of Medical Oncology, Hyogo Cancer Center kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Jikei University School of Medicine kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, National Defense Medical College kn-affil= affil-num=10 en-affil=Department of Gynecologic Oncology, Saitama Cancer Center kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Jichi Medical University kn-affil= affil-num=12 en-affil=Department of Obstetrics and Gynecology, Yokohama City University Hospital kn-affil= affil-num=13 en-affil=Department of Gynecologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=14 en-affil=Department of Gynecologic Oncology, Saitama Medical University International Medical Center kn-affil= affil-num=15 en-affil=Department of Gynecology, Shizuoka Cancer Center kn-affil= affil-num=16 en-affil=Department of Gynecology, Gunma Prefectural Cancer Center kn-affil= affil-num=17 en-affil=Department of Obstetrics and Gynecology, Jikei University School of Medicine kn-affil= affil-num=18 en-affil=Department of Gynecologic Oncology, Saitama Medical University International Medical Center kn-affil= affil-num=19 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Recurrent endometrial cancer kn-keyword=Recurrent endometrial cancer en-keyword=Re-administration of platinum-based chemotherapy kn-keyword=Re-administration of platinum-based chemotherapy en-keyword=Platinum-free interval kn-keyword=Platinum-free interval en-keyword=Secondary platinum response kn-keyword=Secondary platinum response END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=32 article-no= start-page=12686 end-page=12694 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Boosting charge separation in organic photovoltaics: unveiling dipole moment variations in excited non-fullerene acceptor layers en-subtitle= kn-subtitle= en-abstract= kn-abstract=The power conversion efficiency (PCE) of organic photovoltaics (OPVs) has reached more than 19% due to the rapid development of non-fullerene acceptors (NFAs). To compete with the PCEs (26%) of commercialized silicon-based inorganic photovoltaics, the drawback of OPVs should be minimized. This drawback is the intrinsic large loss of open-circuit voltage; however, a general approach to this issue remains elusive. Here, we report a discovery regarding highly efficient NFAs, specifically ITIC. We found that charge-transfer (CT) and charge dissociation (CD) can occur even in a neat ITIC film without the donor layer. This is surprising, as these processes were previously believed to take place exclusively at donor/acceptor heterojunctions. Femtosecond time-resolved visible to mid-infrared measurements revealed that in the neat ITIC layers, the intermolecular CT immediately proceeds after photoirradiation (<0.1 ps) to form weakly-bound excitons with a binding energy of 0.3 eV, which are further dissociated into free electrons and holes with a time-constant of 56 ps. Theoretical calculations indicate that stacking faults in ITIC (i.e., V-type molecular stacking) induce instantaneous intermolecular CT and CD in the neat ITIC layer. In contrast, J-type stacking does not support such CT and CD. This previously unknown pathway is triggered by the larger dipole moment change on the excited state generated at the lower symmetric V-type molecular stacking of ITIC. This is in sharp contrast with the need of sufficient energy offset for CT and CD at the donor-acceptor heterojunction, leading to the significant voltage loss in conventional OPVs. These results demonstrate that the rational molecular design of NFAs can increase the local dipole moment change on the excited state within the NFA layer. This finding paves the way for a groundbreaking route toward the commercialization of OPVs. en-copyright= kn-copyright= en-aut-name=YamakataAkira en-aut-sei=Yamakata en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoKosaku en-aut-sei=Kato en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UrakamiTakumi en-aut-sei=Urakami en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujimuraSota en-aut-sei=Tsujimura en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurayamaKasumi en-aut-sei=Murayama en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigashiMasahiro en-aut-sei=Higashi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoHirofumi en-aut-sei=Sato en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoboriYasuhiro en-aut-sei=Kobori en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UmeyamaTomokazu en-aut-sei=Umeyama en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ImahoriHiroshi en-aut-sei=Imahori en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Molecular Engineering, Graduate School of Engineering, Kyoto University kn-affil= affil-num=4 en-affil=Department of Chemistry, Graduate School of Science, Kobe University kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Science, Kobe University kn-affil= affil-num=6 en-affil=Department of Complex Systems Science, Graduate School of Informatics, Nagoya University kn-affil= affil-num=7 en-affil=Department of Molecular Engineering, Graduate School of Engineering, Kyoto University kn-affil= affil-num=8 en-affil=Department of Chemistry, Graduate School of Science, Kobe University kn-affil= affil-num=9 en-affil=Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo kn-affil= affil-num=10 en-affil=Department of Molecular Engineering, Graduate School of Engineering, Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=6 article-no= start-page=2497 end-page=2509 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Senescent Fibroblasts Potentiate Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells via IL-8–mediated Crosstalk en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Diffuse-type gastric cancer (DGC) often forms peritoneal metastases, leading to poor prognosis. However, the underlying mechanism of DGC-mediated peritoneal metastasis is poorly understood. DGC is characterized by desmoplastic stroma, in which heterogeneous cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs) and senescent CAFs (sCAFs), play a crucial role during tumor progression. This study investigated the CAF subtypes induced by GC cells and the role of sCAFs in peritoneal metastasis of DGC cells. Materials and Methods: Conditioned medium of human DGC cells (KATOIII, NUGC-4) and human intestinal-type GC (IGC) cells (MKN-7, N87) was used to induce CAFs. CAF subtypes were evaluated by analyzing the expression of α–smooth muscle actin (α-SMA), senescence-associated β-galactosidase (SA-β-gal), and p16 in human normal fibroblasts (GF, FEF-3). A cytokine array was used to explore the underlying mechanism of GC-induced CAF subtype development. The role of sCAFs in peritoneal metastasis of DGC cells was analyzed using a peritoneally metastatic DGC tumor model. The relationships between GC subtypes and CAF-related markers were evaluated using publicly available datasets. Results: IGC cells significantly induced α-SMA+ myCAFs by secreting transforming growth factor–β, whereas DGC cells induced SA-β-gal+/p16+ sCAFs by secreting interleukin (IL)-8. sCAFs further secreted IL-8 to promote DGC cell migration. In vivo experiments demonstrated that co-inoculation of sCAFs significantly enhanced peritoneal metastasis of NUGC-4 cells, which was attenuated by administration of the IL-8 receptor antagonist navarixin. p16 and IL-8 expression was significantly associated with poor prognosis of DGC patients. Conclusion: sCAFs promote peritoneal metastasis of DGC via IL-8–mediated crosstalk. en-copyright= kn-copyright= en-aut-name=LIYUNCHENG en-aut-sei=LI en-aut-mei=YUNCHENG kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TAZAWAHIROSHI en-aut-sei=TAZAWA en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NAGAIYASUO en-aut-sei=NAGAI en-aut-mei=YASUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FUJITASHUTO en-aut-sei=FUJITA en-aut-mei=SHUTO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OKURATOMOHIRO en-aut-sei=OKURA en-aut-mei=TOMOHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SHOJIRYOHEI en-aut-sei=SHOJI en-aut-mei=RYOHEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YAMADAMOTOHIKO en-aut-sei=YAMADA en-aut-mei=MOTOHIKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KIKUCHISATORU en-aut-sei=KIKUCHI en-aut-mei=SATORU kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KURODASHINJI en-aut-sei=KURODA en-aut-mei=SHINJI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OHARATOSHIAKI en-aut-sei=OHARA en-aut-mei=TOSHIAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NOMAKAZUHIRO en-aut-sei=NOMA en-aut-mei=KAZUHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NISHIZAKIMASAHIKO en-aut-sei=NISHIZAKI en-aut-mei=MASAHIKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KAGAWASHUNSUKE en-aut-sei=KAGAWA en-aut-mei=SHUNSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=peritoneal metastasis kn-keyword=peritoneal metastasis en-keyword=senescent fibroblast kn-keyword=senescent fibroblast en-keyword=IL-8 kn-keyword=IL-8 en-keyword=CXCR1/2 kn-keyword=CXCR1/2 END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page=1383309 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Late-onset renal variant Fabry disease with R112H mutation and mild increase in plasma globotriaosylsphingosine: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fabry disease (FD) is an X-linked disorder resulting in a deficiency of alpha-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD patients, characterized by a late-onset phenotype, almost normal to mild lyso-Gb3 elevation, and mild clinical symptoms, despite low GLA activity. This is due to the structural features of the R112H GLA protein. We herein report the case of a 42-year-old male patient with late-onset FD with a R112H mutation. The patient exhibited only renal involvement with no other organ damage and was successfully treated with galactosidase beta and subsequent migalastat for approximately 10 years. Especially, migalastat was clinically effective in normalizing plasma lyso-Gb3 levels and inhibiting the progression of renal damage associated with FD. Therefore, the use of migalastat in the FD patients with R112H mutation is highly recommended based on this case report. en-copyright= kn-copyright= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnishiAkifumi en-aut-sei=Onishi en-aut-mei=Akifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaruyamaHiroki en-aut-sei=Maruyama en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Fukuyama City Hospital kn-affil= affil-num=5 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= affil-num=7 en-affil=Department of Clinical Nephroscience, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=8 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University kn-affil= en-keyword=Fabry disease kn-keyword=Fabry disease en-keyword=R112H mutation kn-keyword=R112H mutation en-keyword=migalastat kn-keyword=migalastat en-keyword=proteinuria kn-keyword=proteinuria en-keyword=chronic kidney disease kn-keyword=chronic kidney disease END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=11 article-no= start-page=2632 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=In Vitro Study of Tumor-Homing Peptide-Modified Magnetic Nanoparticles for Magnetic Hyperthermia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer cells have higher heat sensitivity compared to normal cells; therefore, hyperthermia is a promising approach for cancer therapy because of its ability to selectively kill cancer cells by heating them. However, the specific and rapid heating of tumor tissues remains challenging. This study investigated the potential of magnetic nanoparticles (MNPs) modified with tumor-homing peptides (THPs), specifically PL1 and PL3, for tumor-specific magnetic hyperthermia therapy. The synthesis of THP-modified MNPs involved the attachment of PL1 and PL3 peptides to the surface of the MNPs, which facilitated enhanced tumor cell binding and internalization. Cell specificity studies revealed an increased uptake of PL1- and PL3-MNPs by tumor cells compared to unmodified MNPs, indicating their potential for targeted delivery. In vitro hyperthermia experiments demonstrated the efficacy of PL3-MNPs in inducing tumor cell death when exposed to an alternating magnetic field (AMF). Even without exposure to an AMF, an additional ferroptotic pathway was suggested to be mediated by the nanoparticles. Thus, this study suggests that THP-modified MNPs, particularly PL3-MNPs, hold promise as a targeted approach for tumor-specific magnetic hyperthermia therapy. en-copyright= kn-copyright= en-aut-name=ZhouShengli en-aut-sei=Zhou en-aut-mei=Shengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsutsumiuchiKaname en-aut-sei=Tsutsumiuchi en-aut-mei=Kaname kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ImaiRitsuko en-aut-sei=Imai en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MikiYukiko en-aut-sei=Miki en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoAnna en-aut-sei=Kondo en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakagawaHiroshi en-aut-sei=Nakagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=3 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=4 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=5 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=6 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=7 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=tumor-homing peptide kn-keyword=tumor-homing peptide en-keyword=magnetic hyperthermia kn-keyword=magnetic hyperthermia en-keyword=magnetic nanoparticles kn-keyword=magnetic nanoparticles en-keyword=ferroptosis kn-keyword=ferroptosis en-keyword=tumor-specific delivery kn-keyword=tumor-specific delivery END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=3 article-no= start-page=1177 end-page=1189 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of output factors of different radiotherapy planning systems using Exradin W2 plastic scintillator detector en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aims to evaluate the output factors (OPF) of different radiation therapy planning systems (TPSs) using a plastic scintillator detector (PSD). The validation results for determining a practical field size for clinical use were verified. The implemented validation system was an Exradin W2 PSD. The focus was to validate the OPFs of the small irradiation fields of two modeled radiation TPSs using RayStation version 10.0.1 and Monaco version 5.51.10. The linear accelerator used for irradiation was a TrueBeam with three energies: 4, 6, and 10 MV. RayStation calculations showed that when the irradiation field size was reduced from 10 × 10 to 0.5 × 0.5 cm2, the results were within 2.0% of the measured values for all energies. Similarly, the values calculated using Monaco were within approximately 2.0% of the measured values for irradiation field sizes between 10 × 10 and 1.5 × 1.5 cm2 for all beam energies of interest. Thus, PSDs are effective validation tools for OPF calculations in TPS. A TPS modeled with the same source data has different minimum irradiation field sizes that can be calculated. These findings could aid in verification of equipment accuracy for treatment planning requiring highly accurate dose calculations and for third-party evaluation of OPF calculations for TPS. en-copyright= kn-copyright= en-aut-name=AndoYasuharu en-aut-sei=Ando en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoNatsuko en-aut-sei=Matsumoto en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkuhiroKawasaki en-aut-sei=Ikuhiro en-aut-mei=Kawasaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiharaSoichiro en-aut-sei=Ishihara en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KiriuHiroshi en-aut-sei=Kiriu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanabeYoshinori en-aut-sei=Tanabe en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Hiroshima City Hospital kn-affil= affil-num=2 en-affil=Hiroshima City North Medical Center Asa Citizens Hospital kn-affil= affil-num=3 en-affil=Hiroshima City North Medical Center Asa Citizens Hospital kn-affil= affil-num=4 en-affil=Hiroshima City North Medical Center Asa Citizens Hospital kn-affil= affil-num=5 en-affil=Hiroshima City Hospital kn-affil= affil-num=6 en-affil=Hiroshima City Hospital kn-affil= affil-num=7 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=Plastic scintillator kn-keyword=Plastic scintillator en-keyword=Radiation therapy kn-keyword=Radiation therapy en-keyword=Small irradiation field kn-keyword=Small irradiation field en-keyword=Output factor kn-keyword=Output factor END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=36 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sensitivity and specificity of the question “do you have any concerns regarding your mouth related to undergoing surgery?” for predicting perioperative oral health problems in patients with primary esophageal and lung cancer: a retrospective observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Perioperative oral management contributes to the prevention of dental/systemic complications. However, a professional dental checkup before surgery is generally not performed and relies on the patient’s answer to a simple question by medical professionals other than dentists: “Do you have any concerns regarding your mouth related to undergoing surgery?” Here, we evaluated the sensitivity and specificity of this question for predicting perioperative oral health problems in patients with primary esophageal and primary lung cancer.
Methods We performed an oral cavity check in all patients before scheduled surgery for primary esophageal and lung cancer. A total of 183 patients were enrolled (M, 112; F, 71; 24–88 years, median, 69 years), consisting of 61 with primary esophageal cancer (M, 46; F, 15; 24–85 years, median, 69 years) and 122 with primary lung cancer (M, 66; F; 56; 33–88 years, median, 69 years). All subjects provided a response to this question, and an oral cavity check was performed by dentists. The sensitivity and specificity of this question for detecting oral health problems were evaluated retrospectively.
Results Overall sensitivity and specificity for detecting oral health problems were 0.263 and 0.898, respectively. There were no significant differences by sex or disease (primary esophageal or lung cancer).
Conclusion This simple question has low sensitivity but high specificity for detecting oral health problems. Although challenging to detect surgical patients with oral health problems by simply asking questions, the results indicated that patients with oral complaints are more likely to have problems during surgery. en-copyright= kn-copyright= en-aut-name=YoshitomiAiko en-aut-sei=Yoshitomi en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Yamanaka-KohnoReiko en-aut-sei=Yamanaka-Kohno en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Perioperative Management Center, Okayama University Hospital kn-affil= en-keyword=Sensitivity kn-keyword=Sensitivity en-keyword=Specificity kn-keyword=Specificity en-keyword=Perioperative kn-keyword=Perioperative en-keyword=Oral management kn-keyword=Oral management en-keyword=Screening kn-keyword=Screening en-keyword=Question kn-keyword=Question END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=10 article-no= start-page=e4763 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Molecular mechanism of the common and opposing cosolvent effects of fluorinated alcohol and urea on a coiled coil protein en-subtitle= kn-subtitle= en-abstract= kn-abstract=Alcohols and urea are widely used as effective protein denaturants. Among monohydric alcohols, 2,2,2-trifluoroethanol (TFE) has large cosolvent effects as a helix stabilizer in proteins. In contrast, urea efficiently denatures ordered native structures, including helices, into coils. These opposing cosolvent effects of TFE and urea are well known, even though both preferentially bind to proteins; however, the underlying molecular mechanism remains controversial. Cosolvent-dependent relative stability between native and denatured states is rigorously related to the difference in preferential binding parameters (PBPs) between these states. In this study, GCN4-p1 with two-stranded coiled coil helices was employed as a model protein, and molecular dynamics simulations for the helix dimer and isolated coil were conducted in aqueous solutions with 2 M TFE and urea. As 2 M cosolvent aqueous solutions did not exhibit clustering of cosolvent molecules, we were able to directly investigate the molecular origin of the excess PBP without considering the enhancement effect of PBPs arising from the concentration fluctuations. The calculated excess PBPs of TFE for the helices and those of urea for the coils were consistent with experimentally observed stabilization of helix by TFE and that of coil by urea. The former was caused by electrostatic interactions between TFE and side chains of the helices, while the latter was attributed to both electrostatic and dispersion interactions between urea and the main chains. Unexpectedly, reverse-micelle-like orientations of TFE molecules strengthened the electrostatic interactions between TFE and the side chains, resulting in strengthening of TFE solvation. en-copyright= kn-copyright= en-aut-name=NakataNoa en-aut-sei=Nakata en-aut-mei=Noa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkamotoRyuichi en-aut-sei=Okamoto en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SumiTomonari en-aut-sei=Sumi en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KogaKenichiro en-aut-sei=Koga en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaTakeshi en-aut-sei=Morita en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImamuraHiroshi en-aut-sei=Imamura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Information Science, University of Hyogo kn-affil= affil-num=3 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Science, Chiba University kn-affil= affil-num=6 en-affil=Department of Bio-Science, Nagahama Institute of Bio-Science and Technology kn-affil= en-keyword=2,2,2-trifluoroethanol kn-keyword=2,2,2-trifluoroethanol en-keyword=cosolvent effects kn-keyword=cosolvent effects en-keyword=preferential binding parameter kn-keyword=preferential binding parameter en-keyword=protein folding stability kn-keyword=protein folding stability en-keyword=urea kn-keyword=urea END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=7 article-no= start-page=847 end-page=859 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trends and issues in clinical research on satisfaction and quality of life after mastectomy and breast reconstruction: a 5-year scoping review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Breast reconstruction (BR) aims to improve the satisfaction and quality of life (QOL) of breast cancer survivors. Clinical studies using patient-reported outcomes (PROs) can therefore provide relevant information to the patients and support decision-making. This scoping review was conducted to analyze recent trends in world regions, methods used, and factors investigated. The literature search was conducted in August 2022. Databases of PubMed, MEDLINE, and CINAHL were searched for relevant English-language studies published from 2017 to 2022. Studies involving women with breast cancer who underwent BR after mastectomy and investigated PROs after BR using BR-specific scales were included. Data on the country, publication year, study design, PRO measures (PROMs) used, time points of surveys, and research themes were collected. In total, 147 articles met the inclusion criteria. BREAST-Q was the most widely used, contributing to the increase in the number and diversification of studies in this area. Such research has been conducted mainly in North America and Europe and is still developing in Asia and other regions. The research themes involved a wide range of clinical and patient factors in addition to surgery, which could be influenced by research methods, time since surgery, and even cultural differences. Recent BR-specific PROMs have led to a worldwide development of research on factors that affect satisfaction and QOL after BR. PRO after BR may be influenced by local cultural and social features, and it would be necessary to accumulate data in each region to draw clinically useful conclusion. en-copyright= kn-copyright= en-aut-name=SaigaMiho en-aut-sei=Saiga en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagiriRyoko en-aut-sei=Nakagiri en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MukaiYuko en-aut-sei=Mukai en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoHiroshi en-aut-sei=Matsumoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimataYoshihiro en-aut-sei=Kimata en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Plastic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Plastic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Plastic Surgery, Okayama Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Patient-reported outcomes kn-keyword=Patient-reported outcomes en-keyword=Breast reconstruction kn-keyword=Breast reconstruction en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Quality of life kn-keyword=Quality of life en-keyword=Satisfaction kn-keyword=Satisfaction END start-ver=1.4 cd-journal=joma no-vol=72 cd-vols= no-issue=11 article-no= start-page=3787 end-page=3802 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity. en-copyright= kn-copyright= en-aut-name=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoTakuya en-aut-sei=Kato en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoHijiri en-aut-sei=Matsumoto en-aut-mei=Hijiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraSeitaro en-aut-sei=Nishimura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkaiMasaaki en-aut-sei=Akai en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KobayashiTeruki en-aut-sei=Kobayashi en-aut-mei=Teruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Esophageal cancer kn-keyword=Esophageal cancer en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Programmed cell death 1 kn-keyword=Programmed cell death 1 en-keyword=Program cell death ligand 1 kn-keyword=Program cell death ligand 1 en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=e0298292 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fluorescence-guided assessment of bone and soft-tissue sarcomas for predicting the efficacy of telomerase-specific oncolytic adenovirus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas. en-copyright= kn-copyright= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamakawaYasuaki en-aut-sei=Yamakawa en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OmoriToshinori en-aut-sei=Omori en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiuKazuhisa en-aut-sei=Sugiu en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KomatsubaraTadashi en-aut-sei=Komatsubara en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KondoHiroya en-aut-sei=Kondo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MoritaTakuya en-aut-sei=Morita en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KiyonoMasahiro en-aut-sei=Kiyono en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YokooSuguru en-aut-sei=Yokoo en-aut-mei=Suguru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HataToshiaki en-aut-sei=Hata en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakedaKen en-aut-sei=Takeda en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=9 article-no= start-page=1181 end-page=1189 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230423 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic value of the liver fibrosis marker fibrosis-5 index in patients with severe isolated tricuspid regurgitation: comparison with fibrosis-4 index en-subtitle= kn-subtitle= en-abstract= kn-abstract=The fibrosis-4 index (FIB4), a liver fibrosis maker, has been shown to be associated with the prognosis in patients with severe isolated tricuspid regurgitation (TR). Recent study showed that the fibrosis-5 index (FIB5), which was calculated by albumin, alkaline phosphatase, aspartate transaminase, alanine aminotransferase and platelet count, had better prognostic value than FIB4 in patients with heart failure. The aim of this study was to evaluate the usefulness of FIB5 index for predicting prognosis in patients with severe isolated TR and compare the prognostic value between the FIB4 and the FIB5 in those patients. This was a dual-center, retrospective study. 113 consecutive outpatients with severe isolated TR (mean age, 65.8 years; 47.8% male) were analyzed. Major adverse cardiovascular events (MACEs) were defined as the composite of cardiovascular death, hospitalization for heart failure, myocardial infarction, and stroke. During a median follow-up of 3.0 years, 41 MACEs occurred. Patients with MACEs had a lower the FIB5 than patients without MACEs. The multivariate Cox analysis revealed that the FIB5 < -4.30 was significantly associated with higher incidence of MACEs after adjusted by confounding factors. Receiver-operating characteristic curve analyses showed that prognostic values did not differ between the FIB5 and the FIB4 in whole patients and in patients aged ≥ 70 years; while, in patients aged < 70 years, the FIB5 had better prognostic value than the FIB4. The FIB5 may be a useful predictor of MACEs in patients with severe isolated TR. en-copyright= kn-copyright= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakayaMachiko en-aut-sei=Tanakaya en-aut-mei=Machiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoTakaaki en-aut-sei=Saito en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaYusuke en-aut-sei=Katayama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakuragiSatoru en-aut-sei=Sakuragi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Liver disorder kn-keyword=Liver disorder en-keyword=Fibrosis-4 index kn-keyword=Fibrosis-4 index en-keyword=Fibrosis-5 index kn-keyword=Fibrosis-5 index en-keyword=Isolated tricuspid regurgitation kn-keyword=Isolated tricuspid regurgitation en-keyword=Major adverse cardiac events kn-keyword=Major adverse cardiac events END start-ver=1.4 cd-journal=joma no-vol=136 cd-vols= no-issue=4 article-no= start-page=94 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=FLOURY ENDOSPERM 6 mutations enhance the sugary phenotype caused by the loss of ISOAMYLASE1 in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=Starch is a biologically and commercially important glucose polymer synthesized by plants as semicrystalline starch granules (SGs). Because SG morphology affects starch properties, mutants with altered SG morphology may be useful in breeding crops with desirable starch properties, including potentially novel properties. In this study, we employed a simple screen for mutants with altered SG morphology in barley (Hordeum vulgare). We isolated mutants that formed compound SGs together with the normal simple SGs in the endosperm and found that they were allelic mutants of the starch biosynthesis genes ISOAMYLASE1 (HvISA1) and FLOURY ENDOSPERM 6 (HvFLO6), encoding starch debranching enzyme and CARBOHYDRATE-BINDING MODULE 48-containing protein, respectively. We generated the hvflo6 hvisa1 double mutant and showed that it had significantly reduced starch biosynthesis and developed shrunken grains. In contrast to starch, soluble α-glucan, phytoglycogen, and sugars accumulated to higher levels in the double mutant than in the single mutants. In addition, the double mutants showed defects in SG morphology in the endosperm and in the pollen. This novel genetic interaction suggests that hvflo6 acts as an enhancer of the sugary phenotype caused by hvisa1 mutation. en-copyright= kn-copyright= en-aut-name=MatsushimaRyo en-aut-sei=Matsushima en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GalisIvan en-aut-sei=Galis en-aut-mei=Ivan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiuraSatoko en-aut-sei=Miura en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CroftsNaoko en-aut-sei=Crofts en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakenakaYuto en-aut-sei=Takenaka en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OitomeNaoko F. en-aut-sei=Oitome en-aut-mei=Naoko F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshimizuTakeshi en-aut-sei=Ishimizu en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujitaNaoko en-aut-sei=Fujita en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=5 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=6 en-affil=College of Life Sciences, Ritsumeikan University kn-affil= affil-num=7 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=8 en-affil=College of Life Sciences, Ritsumeikan University kn-affil= affil-num=9 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=193 end-page=196 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Laparoscopic Resection Combined with a Transsacral Approach for a Recurrent Tailgut Cyst with a Refractory Fistula en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tailgut cyst is a rare cystic disease of the anterior sacral surface and the remains of an embryonic tail gut. Tailgut cysts have a potential for malignancy, and complete resection with an adequate surgical margin is necessary. Even if incomplete resection does not result in recurrence of malignant disease, there is a risk of local infection leading to refractory fistulas. The optimal treatment for such refractory recurrent lesions has not been reported. We describe a case in which the combination of laparoscopic and transsacral approaches was effective for resecting a recurrent refractory fistula after incomplete resection of a tail gut cyst. en-copyright= kn-copyright= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimamuraHiroshi en-aut-sei=Shimamura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Surgery, Chikuba Hospital for Gastrointestinal and Colorectal Surgery kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=tailgut cyst kn-keyword=tailgut cyst en-keyword=laparoscopic resection kn-keyword=laparoscopic resection en-keyword=fistula formation kn-keyword=fistula formation END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=151 end-page=161 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors’ growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors. en-copyright= kn-copyright= en-aut-name=KomatsubaraTadashi en-aut-sei=Komatsubara en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OmoriToshinori en-aut-sei=Omori en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiuKazuhisa en-aut-sei=Sugiu en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MochizukiYusuke en-aut-sei=Mochizuki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DemiyaKoji en-aut-sei=Demiya en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=soft-tissue sarcoma kn-keyword=soft-tissue sarcoma en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=p53 kn-keyword=p53 en-keyword=BCL-xL kn-keyword=BCL-xL END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=143 end-page=149 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Travel Distance on Surgical Outcomes of Patients Surgically Treated for Non-Small Cell Lung Cancer: A Single-Center Study in Ehime, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Travel burden is a poor prognostic factor for many cancers worldwide because it hinders optimal diagnosis and treatment planning. Currently, the impact of travel burden on survival after surgery for non-small cell lung cancer (NSCLC) in Japan is largely unexplored. We examined the impact of travel distance on the postoperative outcomes of patients with NSCLC in Ehime Prefecture, Japan. The data of 1212 patients who underwent surgical resection for NSCLC were retrospectively reviewed. Patients were divided into quartiles based on the travel distance from their home to the hospital (≤ 13 km, 13-40 km, 40-57 km, and > 57 km) in Ehime Prefecture. We found no significant differences among the quartiles in baseline clinicopathological characteristics, including sex, smoking status, histology, surgical procedure, clinical stage, and pathological stage. Overall survival (OS) and relapse-free survival (RFS) also were not significantly different among the travel distance quartiles. We conclude that travel distance did not impact OS or RFS among patients with NSCLC who underwent surgical resection at our institution. en-copyright= kn-copyright= en-aut-name=ShigematsuHisayuki en-aut-sei=Shigematsu en-aut-mei=Hisayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamashitaNatsumi en-aut-sei=Yamashita en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuehisaHiroshi en-aut-sei=Suehisa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RyukoTsuyoshi en-aut-sei=Ryuko en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiharaTakahito en-aut-sei=Sugihara en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakashimaShohei en-aut-sei=Nakashima en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SanoYoshifumi en-aut-sei=Sano en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=2 en-affil=Clinical Research Center, NHO Shikoku Cancer Center kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Thoracic Surgery, NHO Shikoku Cancer Center kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=travel distance kn-keyword=travel distance en-keyword=travel burden kn-keyword=travel burden en-keyword=lung surgery kn-keyword=lung surgery en-keyword=surgical outcome kn-keyword=surgical outcome END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=3 article-no= start-page=560 end-page=577 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial intelligence to detect noise events in remote monitoring data en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Remote monitoring (RM) of cardiac implantable electrical devices (CIEDs) can detect various events early. However, the diagnostic ability of CIEDs has not been sufficient, especially for lead failure. The first notification of lead failure was almost noise events, which were detected as arrhythmia by the CIED. A human must analyze the intracardiac electrogram to accurately detect lead failure. However, the number of arrhythmic events is too large for human analysis. Artificial intelligence (AI) seems to be helpful in the early and accurate detection of lead failure before human analysis.
Objective: To test whether a neural network can be trained to precisely identify noise events in the intracardiac electrogram of RM data.
Methods: We analyzed 21 918 RM data consisting of 12 925 and 1884 Medtronic and Boston Scientific data, respectively. Among these, 153 and 52 Medtronic and Boston Scientific data, respectively, were diagnosed as noise events by human analysis. In Medtronic, 306 events, including 153 noise events and randomly selected 153 out of 12 692 nonnoise events, were analyzed in a five-fold cross-validation with a convolutional neural network. The Boston Scientific data were analyzed similarly.
Results: The precision rate, recall rate, F1 score, accuracy rate, and the area under the curve were 85.8 ± 4.0%, 91.6 ± 6.7%, 88.4 ± 2.0%, 88.0 ± 2.0%, and 0.958 ± 0.021 in Medtronic and 88.4 ± 12.8%, 81.0 ± 9.3%, 84.1 ± 8.3%, 84.2 ± 8.3% and 0.928 ± 0.041 in Boston Scientific. Five-fold cross-validation with a weighted loss function could increase the recall rate.
Conclusions: AI can accurately detect noise events. AI analysis may be helpful for detecting lead failure events early and accurately. en-copyright= kn-copyright= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BabaKensuke en-aut-sei=Baba en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorookaKen'Ichi en-aut-sei=Morooka en-aut-mei=Ken'Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShiraeHaruto en-aut-sei=Shirae en-aut-mei=Haruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MizunoTomofumi en-aut-sei=Mizuno en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MasudaTakuro en-aut-sei=Masuda en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UeokaAkira en-aut-sei=Ueoka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsadaSaori en-aut-sei=Asada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawadaSatoshi en-aut-sei=Kawada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Cyber-Physical Engineering Informatics Research Core, Okayama University kn-affil= affil-num=3 en-affil=Division of Industrial Innovation Sciences, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Division of Industrial Innovation Sciences, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=five-fold cross-validation kn-keyword=five-fold cross-validation en-keyword=intracardiac electrogram kn-keyword=intracardiac electrogram en-keyword=noise event kn-keyword=noise event en-keyword=remote monitoring kn-keyword=remote monitoring END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=6723 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240320 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of a novel AAK1 inhibitor via Kinobeads-based screening en-subtitle= kn-subtitle= en-abstract= kn-abstract=A chemical proteomics approach using Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor-immobilized sepharose (TIM-063-Kinobeads) identified main targets such as CaMKK alpha/1 and beta/2, and potential off-target kinases, including AP2-associated protein kinase 1 (AAK1), as TIM-063 interactants. Because TIM-063 interacted with the AAK1 catalytic domain and inhibited its enzymatic activity moderately (IC50 = 8.51 mu M), we attempted to identify potential AAK1 inhibitors from TIM-063-derivatives and found a novel AAK1 inhibitor, TIM-098a (11-amino-2-hydroxy-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) which is more potent (IC50 = 0.24 mu M) than TIM-063 without any inhibitory activity against CaMKK isoforms and a relative AAK1-selectivity among the Numb-associated kinases family. TIM-098a could inhibit AAK1 activity in transfected cultured cells (IC50 = 0.87 mu M), indicating cell-membrane permeability of the compound. Overexpression of AAK1 in HeLa cells significantly reduced the number of early endosomes, which was blocked by treatment with 10 mu M TIM-098a. These results indicate TIM-063-Kinobeads-based chemical proteomics is efficient for identifying off-target kinases and re-evaluating the kinase inhibitor (TIM-063), leading to the successful development of a novel inhibitory compound (TIM-098a) for AAK1, which could be a molecular probe for AAK1. TIM-098a may be a promising lead compound for a more potent, selective and therapeutically useful AAK1 inhibitor. en-copyright= kn-copyright= en-aut-name=YoshidaAkari en-aut-sei=Yoshida en-aut-mei=Akari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoFumiya en-aut-sei=Matsumoto en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyagawaTomoyuki en-aut-sei=Miyagawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkinoRei en-aut-sei=Okino en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkedaYumeya en-aut-sei=Ikeda en-aut-mei=Yumeya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TadaNatsume en-aut-sei=Tada en-aut-mei=Natsume kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GotohAkira en-aut-sei=Gotoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HatanoNaoya en-aut-sei=Hatano en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MorishitaRyo en-aut-sei=Morishita en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SunatsukiYukinari en-aut-sei=Sunatsuki en-aut-mei=Yukinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NilssonUlf J. en-aut-sei=Nilsson en-aut-mei=Ulf J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshikawaTeruhiko en-aut-sei=Ishikawa en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TokumitsuHiroshi en-aut-sei=Tokumitsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=4 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=5 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=6 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=11 en-affil=CellFree Sciences Co. Ltd kn-affil= affil-num=12 en-affil=Organelle Systems Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=13 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=14 en-affil=Department of Chemistry, Lund University kn-affil= affil-num=15 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=16 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=626 cd-vols= no-issue=7999 article-no= start-page=670 end-page=677 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240131 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oxygen-evolving photosystem II structures during S1–S2–S3 transitions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosystem II (PSII) catalyses the oxidation of water through a four-step cycle of Si states (i = 0–4) at the Mn4CaO5 cluster1,2,3, during which an extra oxygen (O6) is incorporated at the S3 state to form a possible dioxygen4,5,6,7. Structural changes of the metal cluster and its environment during the S-state transitions have been studied on the microsecond timescale. Here we use pump-probe serial femtosecond crystallography to reveal the structural dynamics of PSII from nanoseconds to milliseconds after illumination with one flash (1F) or two flashes (2F). YZ, a tyrosine residue that connects the reaction centre P680 and the Mn4CaO5 cluster, showed structural changes on a nanosecond timescale, as did its surrounding amino acid residues and water molecules, reflecting the fast transfer of electrons and protons after flash illumination. Notably, one water molecule emerged in the vicinity of Glu189 of the D1 subunit of PSII (D1-E189), and was bound to the Ca2+ ion on a sub-microsecond timescale after 2F illumination. This water molecule disappeared later with the concomitant increase of O6, suggesting that it is the origin of O6. We also observed concerted movements of water molecules in the O1, O4 and Cl-1 channels and their surrounding amino acid residues to complete the sequence of electron transfer, proton release and substrate water delivery. These results provide crucial insights into the structural dynamics of PSII during S-state transitions as well as O–O bond formation. en-copyright= kn-copyright= en-aut-name=LiHongjie en-aut-sei=Li en-aut-mei=Hongjie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NangoEriko en-aut-sei=Nango en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OwadaShigeki en-aut-sei=Owada en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaDaichi en-aut-sei=Yamada en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HashimotoKana en-aut-sei=Hashimoto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LuoFangjia en-aut-sei=Luo en-aut-mei=Fangjia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaRie en-aut-sei=Tanaka en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkitaFusamichi en-aut-sei=Akita en-aut-mei=Fusamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KangJungmin en-aut-sei=Kang en-aut-mei=Jungmin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SaitohYasunori en-aut-sei=Saitoh en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KishiShunpei en-aut-sei=Kishi en-aut-mei=Shunpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YuHuaxin en-aut-sei=Yu en-aut-mei=Huaxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MatsubaraNaoki en-aut-sei=Matsubara en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiiHajime en-aut-sei=Fujii en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SugaharaMichihiro en-aut-sei=Sugahara en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SuzukiMamoru en-aut-sei=Suzuki en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MasudaTetsuya en-aut-sei=Masuda en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KimuraTetsunari en-aut-sei=Kimura en-aut-mei=Tetsunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=ThaoTran Nguyen en-aut-sei=Thao en-aut-mei=Tran Nguyen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YonekuraShinichiro en-aut-sei=Yonekura en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YuLong-Jiang en-aut-sei=Yu en-aut-mei=Long-Jiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=ToshaTakehiko en-aut-sei=Tosha en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=TonoKensuke en-aut-sei=Tono en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=JotiYasumasa en-aut-sei=Joti en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=HatsuiTakaki en-aut-sei=Hatsui en-aut-mei=Takaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=YabashiMakina en-aut-sei=Yabashi en-aut-mei=Makina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KuboMinoru en-aut-sei=Kubo en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=IwataSo en-aut-sei=Iwata en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=IsobeHiroshi en-aut-sei=Isobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=YamaguchiKizashi en-aut-sei=Yamaguchi en-aut-mei=Kizashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=4 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=5 en-affil=Department of Picobiology, Graduate School of Life Science, University of Hyogo kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=8 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=12 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=13 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=14 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=15 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=16 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=17 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=18 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=19 en-affil=Division of Food and Nutrition, Faculty of Agriculture, Ryukoku University kn-affil= affil-num=20 en-affil=Department of Chemistry, Graduate School of Science, Kobe University kn-affil= affil-num=21 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=22 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=23 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=24 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=25 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=26 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=27 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=28 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=29 en-affil=Department of Picobiology, Graduate School of Life Science, University of Hyogo kn-affil= affil-num=30 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=31 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=32 en-affil=Center for Quantum Information and Quantum Biology, Osaka University kn-affil= affil-num=33 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=34 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=1 article-no= start-page=13 end-page=20 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Microtremor exploration in Tsushima Campus, Okayama University kn-title=岡山大学津島キャンパスおける微動探査 en-subtitle= kn-subtitle= en-abstract= kn-abstract=　In this report, microtremor array observations were conducted in the Tsushima Campus of Okayama University, and the subsurface velocity structure was estimated from the analysis of the records. The results indicate that a five-layer S-wave velocity structure from the surface to the seismic basement equivalent layer with thicknesses of 8, 24, 80 and 180 m and velocities of 150, 450, 1100, 1700 and 3200 m/s, respectively, is reasonable. This model explains to some extent the observed phase velocity and H/V spectral ratios. It is also consistent with the surface borehole results. Furthermore, the areal characteristics of the H/V spectral ratios were also presented, allowing us to estimate the trend of the ground structure in shallow areas. en-copyright= kn-copyright= en-aut-name=YAMADANobuyuki en-aut-sei=YAMADA en-aut-mei=Nobuyuki kn-aut-name=山田伸之 kn-aut-sei=山田 kn-aut-mei=伸之 aut-affil-num=1 ORCID= en-aut-name=TAKENAKAHiroshi en-aut-sei=TAKENAKA en-aut-mei=Hiroshi kn-aut-name=竹中博士 kn-aut-sei=竹中 kn-aut-mei=博士 aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Science and Technology, Kochi University kn-affil=高知大学理工学部地球環境防災学科 affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil=岡山大学学術研究院環境生命自然科学学域 en-keyword=Okayama kn-keyword=Okayama en-keyword=Microtremor array exploration kn-keyword=Microtremor array exploration en-keyword=S-wave velocity kn-keyword=S-wave velocity en-keyword=H/V spectral ratio kn-keyword=H/V spectral ratio END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240319 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pericardial Effusion in Association With Periodontitis: Case Report and Review of 8 Patients in Literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontal diseases are well-known background for infective endocarditis. Here, we show that pericardial effusion or pericarditis might have origin also in periodontal diseases. An 86-year-old man with well-controlled hypertension and diabetes mellitus developed asymptomatic increase in pericardial effusion. Two weeks previously, he took oral new quinolone antibiotics for a week because he had painful periodontitis along a dental bridge in the mandibular teeth on the right side and presented cheek swelling. The sputum was positive for Streptococcus species. He was healthy and had a small volume of pericardial effusion for the previous 5 years after drug-eluting coronary stents were inserted at the left anterior descending branch 10 years previously. The differential diagnoses listed for pericardial effusion were infection including tuberculosis, autoimmune diseases, and metastatic malignancy. Thoracic to pelvic computed tomographic scan demonstrated no mass lesions, except for pericardial effusion and a small volume of pleural effusion on the left side. Fluorodeoxyglucose positron emission tomography disclosed many spotty uptakes in the pericardial effusion. The patient denied pericardiocentesis, based on his evaluation of the risk of the procedure. He was thus discharged in several days and followed at outpatient clinic. He underwent dental treatment and pericardial effusion resolved completely in a month. He was healthy in 6 years until the last follow-up at the age of 92 years. We also reviewed 8 patients with pericarditis in association with periodontal diseases in the literature to reveal that periodontal diseases would be the background for developing infective pericarditis and also mediastinitis on some occasions. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuoChie Nakago en-aut-sei=Matsuo en-aut-mei=Chie Nakago kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuoNobuhiko en-aut-sei=Matsuo en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriAyano en-aut-sei=Mori en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiMasaaki en-aut-sei=Murakami en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= affil-num=4 en-affil=Nagashima Hospital kn-affil= affil-num=5 en-affil=Okayama Heart Clinic kn-affil= affil-num=6 en-affil=Okayama University kn-affil= en-keyword=pericardial effusion kn-keyword=pericardial effusion en-keyword=pericarditis kn-keyword=pericarditis en-keyword=periodontitis (periodontal disease) kn-keyword=periodontitis (periodontal disease) en-keyword=positron emission tomography kn-keyword=positron emission tomography en-keyword=Streptococcus kn-keyword=Streptococcus END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=5 article-no= start-page=1074 end-page=1082 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Combined simultaneous endoscopic endonasal and transcranial surgery using high‐definition three‐dimensional exoscope for malignant tumors of the anterior skull base en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Advanced surgical interventions are required to treat malignancies in the anterior skull base (ASB). This study investigates the utility of endoscopic endonasal and transcranial surgery (EETS) using a high-definition three-dimensional exoscope as an alternative to traditional microscopy.
Methods: Six patients with carcinomas of varying histopathologies underwent surgery employing the EETS maneuver, which synchronized three distinct surgical modalities: harvesting of the anterolateral thigh flap, initiation of the transnasal technique, and initiation of the transcranial procedure.
Results: The innovative strategy enabled successful tumor resection and skull base reconstruction without postoperative local neoplastic recurrence, cerebrospinal fluid leakage, or neurological deficits.
Conclusion: The integration of the exoscope and EETS is a novel therapeutic approach for ASB malignancies. This strategy demonstrates the potential of the exoscope in augmenting surgical visualization, enhancing ergonomics, and achieving seamless alignment of multiple surgical interventions. This technique represents a progressive shift in the management of these complex oncological challenges. en-copyright= kn-copyright= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UraguchiKensuke en-aut-sei=Uraguchi en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimizuAiko en-aut-sei=Shimizu en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MuraiAya en-aut-sei=Murai en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigakiTakaya en-aut-sei=Higaki en-aut-mei=Takaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkisadaNaoki en-aut-sei=Akisada en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujimotoShohei en-aut-sei=Fujimoto en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiKentaro en-aut-sei=Fujii en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtaTomoyuki en-aut-sei=Ota en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsumotoHiroshi en-aut-sei=Matsumoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=14 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=15 en-affil=Department of Otolaryngology – Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anterior skull base malignant tumors kn-keyword=anterior skull base malignant tumors en-keyword=anterolateral thigh flap kn-keyword=anterolateral thigh flap en-keyword=endoscopic endonasal and transcranial surgery kn-keyword=endoscopic endonasal and transcranial surgery en-keyword=ORBEYE kn-keyword=ORBEYE en-keyword=skull base reconstruction kn-keyword=skull base reconstruction END start-ver=1.4 cd-journal=joma no-vol=130 cd-vols= no-issue=7 article-no= start-page=1187 end-page=1195 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Pancreatic cancer is an aggressive, immunologically “cold” tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702).
Methods: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps).
Results: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection.
Conclusion: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer. en-copyright= kn-copyright= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KadowakiDaisuke en-aut-sei=Kadowaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakamotoMasaki en-aut-sei=Sakamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamadaYuki en-aut-sei=Hamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugimotoRyoma en-aut-sei=Sugimoto en-aut-mei=Ryoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YagiChiaki en-aut-sei=Yagi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhtaniTomoko en-aut-sei=Ohtani en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KumonKento en-aut-sei=Kumon en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=20 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=7 article-no= start-page=1004 end-page=1014 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The effect of solvent molecules on crystallisation of heterotrinuclear MII–TbIII–MII complexes with tripodal nonadentate ligands en-subtitle= kn-subtitle= en-abstract= kn-abstract=The crystal structures and crystallisation behaviours of MII–TbIII–MII heterotrinuclear complexes, [(L)MTbM(L)]NO3 (M = Mn and Zn; L3− stands for a conjugated base of H3L = 1,1,1-tris[(3-methoxysalicylideneamino)methyl]ethane), obtained from various organic solvents (MeOH, EtOH, CH2Cl2 and CHCl3) were investigated. The trinuclear complex cation has two asymmetric centres (Δ or Λ) at two MII sites as a result of the twisted tripodal arms of L3−. Single-crystal X-ray diffraction analysis revealed that all the analysed Zn–Tb–Zn complexes had homochiral structures (Δ,Δ- or Λ,Λ-enantiomers) in each single crystal; however, the type of crystallisation behaviour showed clear differences depending on the type of solvent molecule. Specifically, crystallisation from MeOH or CH2Cl2 resulted in the exclusive formation of the Λ-conglomerates with the Λ,Λ-enantiomers—a phenomenon we recently termed ‘absolute spontaneous resolution’. The analogous Mn–Tb–Mn complex crystallised from MeOH also resulted in the same phenomenon as that of Zn–Tb–Zn. In contrast, the meso-type (Δ,Λ) achiral isomer of the Mn–Tb–Mn complex was deposited for the first time in a series of MII–LnIII–MII trinuclear complexes from a CH2Cl2 or EtOH solution. Density functional theory calculations were performed to compare the thermodynamic stability of homochiral (Λ,Λ) and meso-type (Δ,Λ) complex cations of [(L)MnTbMn(L)]+ in MeOH and EtOH. Results were consistent with the molecular structures observed in the crystallographic analysis of the compounds deposited from these solvents. en-copyright= kn-copyright= en-aut-name=TakaharaKazuma en-aut-sei=Takahara en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HorinoYuki en-aut-sei=Horino en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaKoki en-aut-sei=Wada en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakataHiromu en-aut-sei=Sakata en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomitaDaichi en-aut-sei=Tomita en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SunatsukiYukinari en-aut-sei=Sunatsuki en-aut-mei=Yukinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IsobeHiroshi en-aut-sei=Isobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KojimaMasaaki en-aut-sei=Kojima en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiTakayoshi en-aut-sei=Suzuki en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Science, Okayama University kn-affil= affil-num=6 en-affil=Advanced Science Research Center, Okayama University kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=11 article-no= start-page=e0294491 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colorectal cancer (CRC) cells harboring KRAS or BRAF mutations show a more-malignant phenotype than cells with wild-type KRAS and BRAF. KRAS/BRAF-wild-type CRCs are sensitive to epidermal growth factor receptor (EGFR)-targeting agents, whereas KRAS/BRAF-mutant CRCs are resistant due to constitutive activation of the EGFR-downstream KRAS/BRAF signaling pathway. Novel therapeutic strategies to treat KRAS/BRAF mutant CRC cells are thus needed. We recently demonstrated that the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 exhibit therapeutic potential against KRAS-mutant human pancreatic cancer cells. In this study, we evaluated the therapeutic potential of OBP-301 and OBP-702 against human CRC cells with differing KRAS/BRAF status. Human CRC cells with wild-type KRAS/BRAF (SW48, Colo320DM, CACO-2), mutant KRAS (DLD-1, SW620, HCT116), and mutant BRAF (RKO, HT29, COLO205) were used in this study. The antitumor effect of OBP-301 and OBP-702 against CRC cells was analyzed using the XTT assay. Virus-mediated modulation of apoptosis, autophagy, and the EGFR-MEK-ERK and AKT-mTOR signaling pathways was analyzed by Western blotting. Wild-type and KRAS-mutant CRC cells were sensitive to OBP-301 and OBP-702, whereas BRAF-mutant CRC cells were sensitive to OBP-702 but resistant to OBP-301. Western blot analysis demonstrated that OBP-301 induced autophagy and that OBP-702 induced autophagy and apoptosis in human CRC cells. In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis. en-copyright= kn-copyright= en-aut-name=TamuraShuta en-aut-sei=Tamura en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HoriNaoto en-aut-sei=Hori en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiYuncheng en-aut-sei=Li en-aut-mei=Yuncheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=1 article-no= start-page=zrad161 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Epidural versus patient-controlled intravenous analgesia on pain relief and recovery after laparoscopic gastrectomy for gastric cancer: randomized clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Epidural analgesia (EDA) is a main modality for postoperative pain relief in major open abdominal surgery within the Enhanced Recovery After Surgery protocol. However, it remains unclear whether EDA is an imperative modality in laparoscopic gastrectomy (LG). This study examined non-inferiority of patient-controlled intravenous analgesia (PCIA) to EDA in terms of postoperative pain and recovery in patients who underwent LG.
Methods: In this open-label, non-inferiority, parallel, individually randomized clinical trial, patients who underwent elective LG for gastric cancer were randomized 1:1 to receive either EDA or PCIA after surgery. The primary endpoint was pain score using the Numerical Rating Scale at rest 24 h after surgery, analysed both according to the intention-to-treat (ITT) principle and per protocol. The non-inferiority margin for pain score was set at 1. Secondary outcomes were postoperative parameters related to recovery and adverse events related to analgesia.
Results: Between 3 July 2017 and 29 September 2020, 132 patients were randomized to receive either EDA (n = 66) or PCIA (n = 66). After exclusions, 64 patients were included in the EDA group and 65 patients in the PCIA group for the ITT analysis. Pain score at rest 24 h after surgery was 1.94 (s.d. 2.07) in the EDA group and 2.63 (s.d. 1.76) in the PCIA group (P = 0.043). PCIA was not non-inferior to EDA for the primary endpoint (difference 0.69, one side 95% c.i. 1.25, P = 0.184) in ITT analysis. Postoperative parameters related to recovery were similar between groups. More EDA patients (21 (32.8%) versus 1 (1.5%), P < 0.001) developed postoperative hypotension as an adverse event.
Conclusions: PCIA was not non-inferior to EDA in terms of early-phase pain relief after LG. Registration number: UMIN000027643 (https://www.umin.ac.jp/ctr/index-j.htm). Conclusions: PCIA was not non-inferior to EDA in terms of early-phase pain relief after LG.Registration number: UMIN000027643 (https://www.umin.ac.jp/ctr/index-j.htm). en-copyright= kn-copyright= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsusakiTakashi en-aut-sei=Matsusaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakataNobuo en-aut-sei=Takata en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitsuiEma en-aut-sei=Mitsui en-aut-mei=Ema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=22028 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bundling of collagen fibrils influences osteocyte network formation during bone modeling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteocytes form a cellular network by gap junctions between their cell processes. This network is important since intercellular communication via the network is essential for bone metabolism. However, the factors that influence the formation of this osteocyte network remain unknown. As the early stage of osteocyte network formation occurs on the bone surface, we observed a newly formed trabecular bone surface by orthogonal focused ion beam-scanning electron microscopy. The embedding late osteoblast processes tended to avoid bundled collagen fibrils and elongate into sparse collagen fibrils. Then, we examined whether the inhibition of bundling of collagen fibrils using a potent lysyl oxidase inhibitor, beta-aminopropionitrile (BAPN) changed the cellular network of the chick calvaria. The osteocyte shape of the control group was spindle-shape, while that of the BAPN group was sphere-shaped. In addition, the osteocyte processes of the control group were elongated vertically to the long axis of the cell body, whereas the osteocyte processes of the BAPN group were elongated radially. Therefore, it was suggested that the bundling of collagen fibrils influences normal osteocyte network formation during bone modeling. en-copyright= kn-copyright= en-aut-name=HashimotoMana en-aut-sei=Hashimoto en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiHaruka en-aut-sei=Takahashi en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Tabata-OkuboKaori en-aut-sei=Tabata-Okubo en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokunagaKazuaki en-aut-sei=Tokunaga en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumoriHaruka en-aut-sei=Matsumori en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshiharaYoshihito en-aut-sei=Ishihara en-aut-mei=Yoshihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KakuMasaru en-aut-sei=Kaku en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IimuraTadahiro en-aut-sei=Iimura en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraToru en-aut-sei=Hara en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Orthodontics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=5 en-affil=Nikon Corporation kn-affil= affil-num=6 en-affil=Nikon Corporation kn-affil= affil-num=7 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Bio‑prosthodontics, Faculty of Dentistry and Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=9 en-affil=Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=10 en-affil=Research Center for Structural Materials, National Institute for Materials Science kn-affil= affil-num=11 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=RP88822 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characterization of tryptophan oxidation affecting D1 degradation by FtsH in the photosystem II quality control of chloroplasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosynthesis is one of the most important reactions for sustaining our environment. Photosystem II (PSII) is the initial site of photosynthetic electron transfer by water oxidation. Light in excess, however, causes the simultaneous production of reactive oxygen species (ROS), leading to photo-oxidative damage in PSII. To maintain photosynthetic activity, the PSII reaction center protein D1, which is the primary target of unavoidable photo-oxidative damage, is efficiently degraded by FtsH protease. In PSII subunits, photo-oxidative modifications of several amino acids such as Trp have been indeed documented, whereas the linkage between such modifications and D1 degradation remains elusive. Here, we show that an oxidative post-translational modification of Trp residue at the N-terminal tail of D1 is correlated with D1 degradation by FtsH during high-light stress. We revealed that Arabidopsis mutant lacking FtsH2 had increased levels of oxidative Trp residues in D1, among which an N-terminal Trp-14 was distinctively localized in the stromal side. Further characterization of Trp-14 using chloroplast transformation in Chlamydomonas indicated that substitution of D1 Trp-14 to Phe, mimicking Trp oxidation enhanced FtsH-mediated D1 degradation under high light, although the substitution did not affect protein stability and PSII activity. Molecular dynamics simulation of PSII implies that both Trp-14 oxidation and Phe substitution cause fluctuation of D1 N-terminal tail. Furthermore, Trp-14 to Phe modification appeared to have an additive effect in the interaction between FtsH and PSII core in vivo. Together, our results suggest that the Trp oxidation at its N-terminus of D1 may be one of the key oxidations in the PSII repair, leading to processive degradation by FtsH. en-copyright= kn-copyright= en-aut-name=KatoYusuke en-aut-sei=Kato en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaHiroshi en-aut-sei=Kuroda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OzawaShin-Ichiro en-aut-sei=Ozawa en-aut-mei=Shin-Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoKeisuke en-aut-sei=Saito en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DograVivek en-aut-sei=Dogra en-aut-mei=Vivek kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ScholzMartin en-aut-sei=Scholz en-aut-mei=Martin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangGuoxian en-aut-sei=Zhang en-aut-mei=Guoxian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=de VitryCatherine en-aut-sei=de Vitry en-aut-mei=Catherine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshikitaHiroshi en-aut-sei=Ishikita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KimChanhong en-aut-sei=Kim en-aut-mei=Chanhong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HipplerMichael en-aut-sei=Hippler en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakahashiYuichiro en-aut-sei=Takahashi en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SakamotoWataru en-aut-sei=Sakamoto en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=4 en-affil=Research Center for Advanced Science and Technology, The University of Tokyo kn-affil= affil-num=5 en-affil=Shanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=6 en-affil=Institute of Plant Biology and Biotechnology, University of Münster kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=8 en-affil=Institut de Biologie Physico-Chimique, Unité Mixte de Recherche 7141, Centre National de la Recherche Scientifique and Sorbonne Université Pierre et Marie Curie kn-affil= affil-num=9 en-affil=Research Center for Advanced Science and Technology, The University of Tokyo kn-affil= affil-num=10 en-affil=Shanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=11 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=12 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=13 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=post-translational modification kn-keyword=post-translational modification en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=protein degradation kn-keyword=protein degradation en-keyword=photosystem II kn-keyword=photosystem II en-keyword=photo-oxidative damage kn-keyword=photo-oxidative damage en-keyword=tryptophan oxidation kn-keyword=tryptophan oxidation en-keyword=Chlamydomonas reinhardtii kn-keyword=Chlamydomonas reinhardtii END start-ver=1.4 cd-journal=joma no-vol=210 cd-vols= no-issue= article-no= start-page=154 end-page=161 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Negative correlations of mitochondrial DNA copy number in commercial frozen bull spermatozoa with the motility parameters after thawing en-subtitle= kn-subtitle= en-abstract= kn-abstract=The purpose of the current study was to investigate the relationship between mitochondrial content of commercial frozen-thawed bull spermatozoa and motility. Firstly, mitochondrial DNA copy number per spermatozoon (MDCN), mitochondrial content (MC), the percentage of spermatozoa with high mitochondrial membrane potential (HMMP), intracellular reactive oxygen species (ROS) and motility parameters of frozen-thawed spermatozoa derived from five bulls were determined by using qPCR, flow cytometry and CASA, respectively, and analyzed the relationships. Results showed that all parameters examined, including MDCN, MC, HMMP, ROS and motility indicators, significantly differed among frozen spermatozoa from different bulls. Both MDCN and MC were negatively correlated with HMMP and motility indicators, but positively with ROS, of course, whereas there was a highly positive relationship between MDCN and MC. Secondly, when MDCN and MC were examined in frozen spermatozoa prepared at different points in the lives of four bulls, those did not correlate overall throughout their lives (1.3–14.3 years old), but did correlate significantly in two sires. From these results, we conclude that MDCN and MC of frozen spermatozoa differ among sires, and are negatively correlated with HMMP and sperm motility parameters, probably due to mitochondrial oxidative stress resulted in the presence of ROS, demonstrating that these appear to be useful markers to assess sires’ spermatozoa. It should be noted that the MDCN and MC of bull spermatozoa may not vary overall with the age of the sire, whereas those changes with age in some individuals and may affect sperm motility. en-copyright= kn-copyright= en-aut-name=NguyenHai Thanh en-aut-sei=Nguyen en-aut-mei=Hai Thanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DoSon Quang en-aut-sei=Do en-aut-mei=Son Quang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiHiroshi en-aut-sei=Kobayashi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FunahashiHiroaki en-aut-sei=Funahashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Okayama Prefectural Center for Animal Husbandry and Research kn-affil= affil-num=4 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Spermatozoa kn-keyword=Spermatozoa en-keyword=Bulls kn-keyword=Bulls en-keyword=Mitochondrial content kn-keyword=Mitochondrial content en-keyword=Motility kn-keyword=Motility en-keyword=Frozen semen kn-keyword=Frozen semen END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=10 article-no= start-page=641 end-page=649 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Syncope and loss of consciousness after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: Prevalence and characteristics in long-term follow-up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Syncope is a significant prognostic factor in patients with Brugada syndrome (BrS). However, the risk of ventricular arrhythmia in patients with nonarrhythmic loss of consciousness (LOC) is similar to that in asymptomatic patients. LOC events after implantable cardioverter-defibrillator (ICD) implantation may provide insights into underlying causes of the initial LOC episode.
Objective The purpose of this study was to examine LOC characteristics following ICD implantation.
Methods We retrospectively analyzed 112 patients with BrS (mean age 47 years; 111 men) who were treated with an ICD. The patients were classified into 3 groups based on symptoms at implantation: asymptomatic (35 patients); LOC (46 patients); and ventricular tachyarrhythmia (VTA) (31 patients). We evaluated the incidence and cause of LOC during long-term follow-up after ICD implantation.
Results During mean follow-up of 12.2 years, 41 patients (37%) experienced LOC after ICD implantation. Arrhythmic LOC occurred in 5 asymptomatic patients, 14 LOC patients, and 16 patients with VTA. Nonarrhythmic LOC, similar to the initial episode, occurred after ICD implantation in 6 patients with prior LOC (2 with neurally mediated syncope and 4 with epilepsy). Most epileptic patients experienced LOC during rest or sleeping, and did not show an abnormal encephalogram during initial evaluation of the LOC episodes.
Conclusion After ICD implantation, 13% of patients had nonarrhythmic LOC similar to the initial episode. Accurate classification of LOC based on a detailed medical history is important for risk stratification, although distinguishing arrhythmic LOC from epilepsy-related LOC episodes can be challenging depending on the circumstances and characteristics of the LOC event. en-copyright= kn-copyright= en-aut-name=AsadaSaori en-aut-sei=Asada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MizunoTomofumi en-aut-sei=Mizuno en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasudaTakuro en-aut-sei=Masuda en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UeokaAkira en-aut-sei=Ueoka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawadaSatoshi en-aut-sei=Kawada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Brugada syndrome kn-keyword=Brugada syndrome en-keyword=Implantable cardioverter-defibrillator kn-keyword=Implantable cardioverter-defibrillator en-keyword=Syncope kn-keyword=Syncope en-keyword=Neurally mediated syncope kn-keyword=Neurally mediated syncope en-keyword=Epilepsy kn-keyword=Epilepsy en-keyword=Ventricular tachyarrhythmia kn-keyword=Ventricular tachyarrhythmia END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue= article-no= start-page=100418 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collapse-related traumatic intracranial hemorrhage following out-of-hospital cardiac arrest: A multicenter retrospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Sudden loss of consciousness as a result of cardiac arrest can cause severe traumatic head injury. Collapse-related traumatic intracranial hemorrhage (CRTIH) following out-of-hospital cardiac arrest (OHCA) may be linked to poor neurological outcomes; however, there is a paucity of data on this entity. This study aimed to investigate the frequency, characteristics, and outcomes of CRTIH following OHCA.
Methods: Adult patients treated post-OHCA at 5 intensive care units who had head computed tomography (CT) scans were included in the study. CRTIH following OHCA was defined as a traumatic intracranial injury from collapse due to sudden loss of consciousness associated with OHCA. Patients with and without CRTIH were compared. The primary outcome assessed was the frequency of CRTIH following OHCA. Additionally, the clinical features, management, and consequences of CRTIH were analyzed descriptively.
Results: CRTIH following OHCA was observed in 8 of 345 enrolled patients (2.3%). CRTIH was more frequent after collapse outside the home, from a standing position, or due to cardiac arrest with a cardiac etiology. Intracranial hematoma expansion on follow up CT was seen in 2 patients; both received anticoagulant therapy, and one required surgical evacuation. Three patients (37.5%) with CRTIH had favorable neurological outcomes 28 days after collapse.
Conclusions: Despite its rare occurrence, physicians should pay special attention to CRTIH following OHCA during the post-resuscitation care period. Larger prospective studies are warranted to provide a more explicit picture of this clinical condition. en-copyright= kn-copyright= en-aut-name=InoueFumiya en-aut-sei=Inoue en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IchibaToshihisa en-aut-sei=Ichiba en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtaniTakayuki en-aut-sei=Otani en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaitoHiroshi en-aut-sei=Naito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KosakiYoshinori en-aut-sei=Kosaki en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurakamiYuya en-aut-sei=Murakami en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IidaAtsuyoshi en-aut-sei=Iida en-aut-mei=Atsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Emergency Medicine, Hiroshima City Hospital kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Emergency Medicine, Hiroshima City Hospital kn-affil= affil-num=4 en-affil=Department of Emergency Medicine, Hiroshima City Hospital kn-affil= affil-num=5 en-affil=Department of Emergency Medicine, Hiroshima City Hospital kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Cardiac arrest kn-keyword=Cardiac arrest en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Craniocerebral trauma kn-keyword=Craniocerebral trauma en-keyword=Intracranial hemorrhage kn-keyword=Intracranial hemorrhage en-keyword=Out-of-hospital cardiac arrest kn-keyword=Out-of-hospital cardiac arrest END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=2 article-no= start-page=307 end-page=316 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Significant delayed conduction and characteristic ventricular tachycardias in patients with cardiac sarcoidosis and electrical storm en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Electrical storm (ES) of ventricular tachyarrhythmias (VTAs) is an important cause of sudden death in patients with cardiac sarcoidosis (CS). VTAs in CS are associated with myocardial scarring and inflammation. However, little is known about the risk factors of ES in patients with CS and VTAs. The objective of this study is to clarify the characteristics and risk factors for the development of ES in patients with CS.
Methods: The study population included consecutive 52 patients with CS and sustained VTA. Twenty-five out of 52 patients experienced ES. We evaluated clinical characteristics, imaging modalities, and electrocardiogram (ECG) parameters to determine the risk factors associated with ES.
Results: Half of the patients experienced VTAs as the initial symptom of sarcoidosis, and eight patients had ES as the initial VTA episode. There were no differences in cardiac imaging abnormalities between patients with and without ES. Among ECG markers, significant QRS fragmentation (odds ratio [OR]: 7.9, p = .01) and epsilon waves (OR: 12.24, p = .02) were associated with ES. Among the ventricular tachycardia (VT) characteristics, multiple morphologies of monomorphic VTs (OR: 10.9, p < .01), short VT cycle lengths (OR: 12.5, p < .01), and polymorphic VT (OR: 13.5, p < .01) were associated with ES. Bidirectional VTs were detected in 10 patients with ES and one patient without ES. Immunosuppressive therapy relieved ES in some patients.
Conclusions: ES was common in patients with CS and VTAs. Significant depolarization abnormalities that appeared as QRS fragmentation, epsilon waves, and specific VT characteristics were associated with ES.
en-copyright= kn-copyright= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UeokaAkira en-aut-sei=Ueoka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizunoTomofumi en-aut-sei=Mizuno en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasudaTakuro en-aut-sei=Masuda en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaSaori en-aut-sei=Asada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawadaSatoshi en-aut-sei=Kawada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=9 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= en-keyword=cardiac sarcoidosis kn-keyword=cardiac sarcoidosis en-keyword=ventricular tachycardia kn-keyword=ventricular tachycardia en-keyword=electrical storm kn-keyword=electrical storm en-keyword=ventricular fibrillation kn-keyword=ventricular fibrillation en-keyword=sudden cardiac death kn-keyword=sudden cardiac death END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=24 article-no= start-page=17294 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors en-subtitle= kn-subtitle= en-abstract= kn-abstract=S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes. en-copyright= kn-copyright= en-aut-name=HoangLoc Dinh en-aut-sei=Hoang en-aut-mei=Loc Dinh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AoyamaEriko en-aut-sei=Aoyama en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiasaMiki en-aut-sei=Hiasa en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OmoteHiroshi en-aut-sei=Omote en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=S-adenosylmethionine kn-keyword=S-adenosylmethionine en-keyword=chondrocyte differentiation kn-keyword=chondrocyte differentiation en-keyword=CCN2 kn-keyword=CCN2 en-keyword=polyamine kn-keyword=polyamine en-keyword=ODC kn-keyword=ODC en-keyword=gene expression kn-keyword=gene expression END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue=3 article-no= start-page=152 end-page=157 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A 4th step of visual art instruction in medical education kn-title=医学における「ビジュアルアート教育」の展開：第４ステップ― 医学教育に必要な“気づき”を与える授業― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KimataYoshihiro en-aut-sei=Kimata en-aut-mei=Yoshihiro kn-aut-name=木股敬裕 kn-aut-sei=木股 kn-aut-mei=敬裕 aut-affil-num=1 ORCID= en-aut-name=ObikaMikako en-aut-sei=Obika en-aut-mei=Mikako kn-aut-name=小比賀美香子 kn-aut-sei=小比賀 kn-aut-mei=美香子 aut-affil-num=2 ORCID= en-aut-name=KuboTakuya en-aut-sei=Kubo en-aut-mei=Takuya kn-aut-name=久保卓也 kn-aut-sei=久保 kn-aut-mei=卓也 aut-affil-num=3 ORCID= en-aut-name=OtsukaMasumi en-aut-sei=Otsuka en-aut-mei=Masumi kn-aut-name=大塚益美 kn-aut-sei=大塚 kn-aut-mei=益美 aut-affil-num=4 ORCID= en-aut-name=OkamotoYuko en-aut-sei=Okamoto en-aut-mei=Yuko kn-aut-name=岡本裕子 kn-aut-sei=岡本 kn-aut-mei=裕子 aut-affil-num=5 ORCID= en-aut-name=FukutomiKoh en-aut-sei=Fukutomi en-aut-mei=Koh kn-aut-name=福冨幸 kn-aut-sei=福冨 kn-aut-mei=幸 aut-affil-num=6 ORCID= en-aut-name=MatsumotoHiroshi en-aut-sei=Matsumoto en-aut-mei=Hiroshi kn-aut-name=松本洋 kn-aut-sei=松本 kn-aut-mei=洋 aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil=岡山大学病院　形成再建外科 affil-num=2 en-affil=Department of General Medicine, Okayama University Hospital kn-affil=岡山大学病院　総合内科・総合診療科 affil-num=3 en-affil=Department of Emergency and Critical Care Medicine, Okayama University Hospital kn-affil=岡山大学病院　救命救急科 affil-num=4 en-affil=OTSUKA DESIGN Co., Ltd. kn-affil=株式会社大塚デザイン affil-num=5 en-affil=Okayama Prefectural Museum of Art kn-affil=岡山県立美術館 affil-num=6 en-affil=Okayama Prefectural Museum of Art kn-affil=岡山県立美術館 affil-num=7 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil=岡山大学病院　形成再建外科 END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue= article-no= start-page=290 end-page=298 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A Meiji person's impression of the petition: What the postscript tells kn-title=建白書ヲ読ミテ ―識語の語るもの― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YAMASHITAHiroshi en-aut-sei=YAMASHITA en-aut-mei=Hiroshi kn-aut-name=山下洋 kn-aut-sei=山下 kn-aut-mei=洋 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=6 article-no= start-page=651 end-page=653 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prenatal Torsion of Radial Polydactyly: A Gangrenous Mass at the Base of the Thumb en-subtitle= kn-subtitle= en-abstract= kn-abstract=A patient was born with a mass at the base of the thumb approximately 1.5 cm in diameter on the radial side of the fingers. The mass had globular swelling filled with hemorrhagic fluid and was dark red. X-rays and histology of the excised specimen suggested the diagnosis of gangrene and torsion of polydactyly. Prenatal torsion of polydactyly is not a common occurrence; moreover, prenatal torsion of polydactyly has only been found in ulnar polydactyly. Our case is a novel case of radial polydactyly that was gangrenous at birth owing to prenatal torsion. Diagnosing such a mass at the base of the thumb is important. en-copyright= kn-copyright= en-aut-name=WatanabeDaisuke en-aut-sei=Watanabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasebeYohei en-aut-sei=Hasebe en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuiHiroshi en-aut-sei=Mitsui en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OishiNaoki en-aut-sei=Oishi en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KasaiShin en-aut-sei=Kasai en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkahaneKoshi en-aut-sei=Akahane en-aut-mei=Koshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KojikaSatoru en-aut-sei=Kojika en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InukaiTakeshi en-aut-sei=Inukai en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=2 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=3 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=4 en-affil=Department of Pathology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=5 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=6 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=7 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=8 en-affil=Department of Pediatrics, Faculty of Medicine, University of Yamanashi kn-affil= en-keyword=infant kn-keyword=infant en-keyword=fingers kn-keyword=fingers en-keyword=thumb kn-keyword=thumb en-keyword=polydactyly kn-keyword=polydactyly en-keyword=torsion abnormality kn-keyword=torsion abnormality END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Pacsin 2依存的なN-カドヘリンの細胞内取り込みが悪性がんの運動様式を制御する kn-title=Pacsin 2-dependent N-cadherin internalization regulates the migration behaviour of malignant cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WINTHAYMAR en-aut-sei=WINT en-aut-mei=HAYMAR kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=化学療法誘発性末梢神経障害モデルラットの前脛骨部筋膜におけるヒアルロン酸合成酵素およびヒアルロン酸含有細胞の減少 kn-title=Decreased expression of hyaluronan synthase and loss of hyaluronan-rich cells in the anterior tibial fascia of the rat model of chemotherapy-induced peripheral neuropathy en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WANGRUILIN en-aut-sei=WANG en-aut-mei=RUILIN kn-aut-name=王瑞林 kn-aut-sei=王 kn-aut-mei=瑞林 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=心肺蘇生は大脳皮質におけるグルタミン酸放出を停止させない可能性がある kn-title=Cardiopulmonary Resuscitation May Not Stop Glutamate Release in the Cerebral Cortex en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FUSHIMIMiki en-aut-sei=FUSHIMI en-aut-mei=Miki kn-aut-name=伏見美紀 kn-aut-sei=伏見 kn-aut-mei=美紀 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=RNA編集は潰瘍性大腸炎関連発癌を予測する有用なバイオマーカーである kn-title=RNA Editing is a Valuable Biomarker for Predicting Carcinogenesis in Ulcerative Colitis en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TAKAHASHIKazutaka en-aut-sei=TAKAHASHI en-aut-mei=Kazutaka kn-aut-name=髙橋一剛 kn-aut-sei=髙橋 kn-aut-mei=一剛 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue=2 article-no= start-page=1 end-page=14 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Building a perspective on the innovation process of local public services kn-title=地方公共サービス革新プロセスの視座の構築 en-subtitle= kn-subtitle= en-abstract= kn-abstract=　When local governments develop public services, they often experience innovation processes. More often, the innovation processes referred to here seem to be the perceived needs for transformation faced with external pressures and the purposive responses to them. This article tries to depict this discourse from a different viewpoint. One of the perspectives that has been proposed so far is that the external environments are made up of multiple actors, and that the historical backgrounds and the relationships between these actors affect the structure of administrative organizations and the methods of providing public services. The transformation processes could be one-time events no matter how long the processes may take, but this article tries to argue they may connote a circular mechanism where both of the administrative organizations and the external actors feedback to each other. In order to elaborate this direction of theorizing, three steps are employed by applying existent literature of various types developed in rather a broader context of social sciences. First, if one of the goals of postmodern theorization is liberating the psychological energies of actors from the cramped social reality that structuralists postulated, then Actor-Network-Theory may be useful. Second, according to Sarasbathy’s research on entrepreneurial behaviors, the view that we effectuate our future through what we can do now is attractive in order to create a new discourse of social innovations, where we appreciate them as not springing out of nowhere all of sudden. Third, once this article accepts polyphonic views on social realities where congested discourses interact during abovementioned process, the role of civic entrepreneurs on the frontline can never be overstated enough. This is because such civic entrepreneurs could cooperate with minority opinions and raise them into broader contexts of dialogues within societies. en-copyright= kn-copyright= en-aut-name=FujiiDaiji en-aut-sei=Fujii en-aut-mei=Daiji kn-aut-name=藤井大児 kn-aut-sei=藤井 kn-aut-mei=大児 aut-affil-num=1 ORCID= en-aut-name=KanajiHiroshi en-aut-sei=Kanaji en-aut-mei=Hiroshi kn-aut-name=金治宏 kn-aut-sei=金治 kn-aut-mei=宏 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=2 en-affil= kn-affil=京都光華女子大学キャリア形成学部 en-keyword=local government kn-keyword=local government en-keyword=public services kn-keyword=public services en-keyword=innovation process kn-keyword=innovation process END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=5 article-no= start-page=054001 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220321 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Experiment and numerical simulation of the combined effect of winding, cool-down, and screening current induced stresses in REBCO coils en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper overviews the combined effects of winding, cool-down, and screening current-induced stresses in REBCO coils. First, a simulation method to model the circumferential stress modification effect due to the screening-current is overviewed. The simulation includes coil winding, cooling down, and coil charge up to the operating current. Second, we will compare the numerical simulation results with the experimental results. The numerical simulations for a dry coil and an epoxy impregnated coil agree well with the experimental results. Third, the enhanced circumferential stress did not degrade the performance of a dry winding REBCO coil, but the improved increased compressive stress buckled the coil structure. Finally, it is demonstrated that epoxy impregnation has beneficial effects in reducing the stress modification effect. However, the circumferential stress is enormously enhanced at the coil ends, sometimes resulting in degradation of the coil performance. en-copyright= kn-copyright= en-aut-name=UedaHiroshi en-aut-sei=Ueda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaHideaki en-aut-sei=Maeda en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuetomiYu en-aut-sei=Suetomi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanagisawaYoshinori en-aut-sei=Yanagisawa en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Japan Science and Technology Agency kn-affil= affil-num=3 en-affil=RIKEN Center for Biosystems Dynamics Research kn-affil= affil-num=4 en-affil=RIKEN Center for Biosystems Dynamics Research kn-affil= en-keyword=REBCO magnet kn-keyword=REBCO magnet en-keyword=screening current kn-keyword=screening current en-keyword=mechanical stress kn-keyword=mechanical stress en-keyword=combined effect kn-keyword=combined effect END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=42 article-no= start-page=11914 end-page=11923 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231017 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An emissive charge-transfer excited-state at the well-defined hetero-nanostructure interface of an organic conjugated molecule and two-dimensional inorganic nanosheet en-subtitle= kn-subtitle= en-abstract= kn-abstract=Precise engineering of excited-state interactions between an organic conjugated molecule and a two-dimensional semiconducting inorganic nanosheet, specifically the manipulation of charge-transfer excited (CTE) states, still remains a challenge for state-of-the-art photochemistry. Herein, we report a long-lived, highly emissive CTE state at structurally well-defined hetero-nanostructure interfaces of photoactive pyrene and two-dimensional MoS2 nanosheets via an N-benzylsuccinimide bridge (Py-Bn-MoS2). Spectroscopic measurements reveal that no charge-transfer state is formed in the ground state, but the locally-excited (LE) state of pyrene in Py-Bn-MoS2 efficiently generates an unusual emissive CTE state. Theoretical studies elucidate the interaction of MoS2 vacant orbitals with the pyrene LE state to form a CTE state that shows a distinct solvent dependence of the emission energy. This is the first example of organic-inorganic 2D hetero-nanostructures displaying mixed luminescence properties by an accurate design of the bridge structure, and therefore represents an important step in their applications for energy conversion and optoelectronic devices and sensors. en-copyright= kn-copyright= en-aut-name=UmeyamaTomokazu en-aut-sei=Umeyama en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MizutaniDaizu en-aut-sei=Mizutani en-aut-mei=Daizu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkedaYuki en-aut-sei=Ikeda en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OsterlohW. Ryan en-aut-sei=Osterloh en-aut-mei=W. Ryan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoFuta en-aut-sei=Yamamoto en-aut-mei=Futa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoKosaku en-aut-sei=Kato en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamakataAkira en-aut-sei=Yamakata en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HigashiMasahiro en-aut-sei=Higashi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UrakamiTakumi en-aut-sei=Urakami en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoHirofumi en-aut-sei=Sato en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ImahoriHiroshi en-aut-sei=Imahori en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo kn-affil= affil-num=2 en-affil=Department of Molecular Engineering, Graduate School of Engineering, Kyoto University kn-affil= affil-num=3 en-affil=Department of Molecular Engineering, Graduate School of Engineering, Kyoto University kn-affil= affil-num=4 en-affil=Department of Molecular Engineering, Graduate School of Engineering, Kyoto University kn-affil= affil-num=5 en-affil=Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo kn-affil= affil-num=6 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Department of Molecular Engineering, Graduate School of Engineering, Kyoto University kn-affil= affil-num=9 en-affil=Department of Molecular Engineering, Graduate School of Engineering, Kyoto University kn-affil= affil-num=10 en-affil=Department of Molecular Engineering, Graduate School of Engineering, Kyoto University kn-affil= affil-num=11 en-affil=Department of Molecular Engineering, Graduate School of Engineering, Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=155 cd-vols= no-issue= article-no= start-page=105797 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ruxolitinib altered IFN-β induced necroptosis of human dental pulp stem cells during osteoblast differentiation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: This study aimed to evaluate the role of ruxolitinib in the interferon beta (IFN-β) mediated osteoblast differentiation using human dental pulp stem cells (hDPSCs).
Design: hDPSCs from five deciduous teeth of healthy patients were stimulated by adding human recombinant IFN-β protein (1 or 2 ng/ml) to the osteogenic differentiation induction medium. Substrate formation was determined using Alizarin Red staining, calcium concentration, and osteoblast marker expression levels. Ruxolitinib was used to inhibit the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway. Apoptosis was detected using terminal deoxynucleotidyl nick-end labeling (TUNEL) staining, and necroptosis was detected using propidium iodide staining and phosphorylated mixed lineage kinase domain-like protein (pMLKL) expression.
Results: In the IFN-β-treated group, substrate formation was inhibited by a reduction in alkaline phosphatase (ALP) expression in a concentration-dependent manner. Although the proliferation potency was unchanged between the IFN-β-treated and control groups, the cell number was significantly reduced in the experimental group. TUNEL-positive cell number was not significantly different; however, the protein level of necroptosis markers, interleukin-6 (IL-6) and pMLKL were significantly increased in the substrate formation. Cell number and ALP expression level were improved in the group administered ruxolitinib, a JAK-STAT inhibitor. Additionally, ruxolitinib significantly suppressed IL-6 and pMLKL levels.
Conclusion: Ruxolitinib interfered with the IFN-β-mediated necroptosis and osteogenic differentiation via the JAK-STAT pathway. en-copyright= kn-copyright= en-aut-name=TanakaAtsuko en-aut-sei=Tanaka en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayanoSatoru en-aut-sei=Hayano en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagataMasayo en-aut-sei=Nagata en-aut-mei=Masayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KosamiTakahiro en-aut-sei=Kosami en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Orthodontics, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Orthodontics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Type-I interferon kn-keyword=Type-I interferon en-keyword=Janus kinase/signal transducers and activators of transcription pathway kn-keyword=Janus kinase/signal transducers and activators of transcription pathway en-keyword=Osteoblast kn-keyword=Osteoblast en-keyword=Necroptosis kn-keyword=Necroptosis en-keyword=Singleton-Merten Syndrome kn-keyword=Singleton-Merten Syndrome END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=553 end-page=559 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Favorable Outcome of Repeated Salvage Surgeries for Rare Metastasis to the Ligamentum Teres Hepatis and the Upper Abdominal Wall in a Stage IV Gastric Cancer Patient en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only four known cases. Herein, we report salvage surgery of successive metastases to the abdominal wall and LTH in a patient originally presenting with advanced gastric cancer with peritoneal metastasis, leading to long-term survival. A 72-year-old man with advanced gastric cancer underwent curative-intent distal gastrectomy with D2 lymph node dissection for gastric outlet obstruction. During this procedure, three small peritoneal metastases were detected in the lesser omentum, the small mesentery, and the mesocolon; however, intraoperative abdominal lavage cytology was negative. We added cytoreductive surgery for peritoneal metastasis. The pathological diagnosis of the gastric cancer was tubular adenocarcinoma with pT4aN1pM1(PER/P1b)CY0 stage IV (Japanese classification of gastric carcinoma/JCGC 15th), or T4N1M1b stage IV (UICC 7th). Post-operative adjuvant chemotherapy with S-1 (TS-1)+cisplatin (CDDP) was administered for 8 months followed by S-1 monotherapy for 4 months. At 28 months after the initial surgery, a follow-up computed tomography (CT) detected a small mass beneath the upper abdominal wall. The ass showed mild avidity on 18F-fluorodeoxyglucose positron-emission (FDG-PET) CT. Salvage resection was performed for diagnosis and treatment, and pathological findings were consistent with primary gastric cancer metastasis. At 49 months after the initial gastrectomy, a new lesion was detected in the LTH with a similar level of avidity on FDG-PET CT as the abdominal wall metastatic lesion. We performed a second salvage surgery for the LTH tumor, which also showed pathology of gastric cancer metastasis. There has been no recurrence up to 1 year after the LTH surgery. With multidisciplinary treatment the patient has survived almost 5 years after the initial gastrectomy. Curative-intent gastrectomy with cytoreductive surgery followed by adjuvant chemotherapy for advanced gastric cancer with localized peritoneal metastasis might have had a survival benefit in our patient. Successive salvage surgeries for oligometastatic lesions in the abdominal wall and the LTH also yielded favorable outcomes. en-copyright= kn-copyright= en-aut-name=MurokawaTakahiro en-aut-sei=Murokawa en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakamotoShinya en-aut-sei=Sakamoto en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuiKenta en-aut-sei=Sui en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzakiKazuhide en-aut-sei=Ozaki en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoManabu en-aut-sei=Matsumoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataJun en-aut-sei=Iwata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshidaHiroshi en-aut-sei=Yoshida en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=9 en-affil=Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School kn-affil= en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=peritoneal metastasis kn-keyword=peritoneal metastasis en-keyword=ligamentum teres hepatis kn-keyword=ligamentum teres hepatis en-keyword=oligometastasis kn-keyword=oligometastasis en-keyword=salvage surgery kn-keyword=salvage surgery END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=537 end-page=543 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationship of Intraoperative SpO2 and ETCO2 Values with Postoperative Hypoxemia in Elderly Patients after Non-Cardiac Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Elderly patients are at higher risk of postoperative hypoxemia due to their decreased respiratory function. The aim of this study was to investigate the relationship of intraoperative oxygen saturation (SpO2) and end-expiratory carbon dioxide (ETCO2) values with postoperative hypoxemia in elderly patients. The inclusion criteria were: 1) patients aged≥75 years; 2) underwent general anesthesia in non-cardiac surgery; 3) operative time longer than two hours; and 4) admission to the intensive care unit (ICU) following surgery performed between January and December 2019. Intraoperative SpO2 and ETCO2 values were collected every minute for the first two hours during surgery. The 253 patients were divided into two groups: SpO2≥92% and SpO2<92%. The time-weighted averages of intraoperative SpO2 and ETCO2 were used to compare differences between the two groups. The incidence of postoperative hypoxemia was 22.5%. For similar ventilator settings, patients with postoperative hypoxemia had lower intraoperative SpO2 and higher ETCO2 values. Sex, ASA classification, and intraoperative SpO2 were independent risk factors for postoperative hypoxemia. In conclusion, postoperative SpO2<92% was a frequent occurrence (> 20%) in elderly patients who underwent major non-cardiac surgery. Postoperative hypoxemia was associated with low intraoperative SpO2 and relatively higher ETCO2. en-copyright= kn-copyright= en-aut-name=SongQingqing en-aut-sei=Song en-aut-mei=Qingqing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PanYu en-aut-sei=Pan en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanazawaTomoyuki en-aut-sei=Kanazawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=oxygen saturation kn-keyword=oxygen saturation en-keyword=end-expiratory carbon dioxide kn-keyword=end-expiratory carbon dioxide en-keyword=postoperative hypoxemia kn-keyword=postoperative hypoxemia END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=499 end-page=509 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurological Analysis Based on the Terminal End of the Spinal Cord and the Narrowest Level of Injured Spine in Thoracolumbar Spinal Injuries en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to clarify neurological differences among the epiconus, conus medullaris, and cauda equina syndromes. Eighty-seven patients who underwent surgery for acute thoracolumbar spinal injuries were assessed. We defined the epiconus as the region from the terminal end of the spinal cord to the proximal 1.0 to 2.25 vertebral bodies, the conus medullaris as the region proximal to < 1.0 vertebral bodies, and the cauda equina as the distal part of the nerve roots originating from the spinal cord. On the basis of the distance from the terminal end of the spinal cord to the narrowest level of the spinal canal, the narrowest levels were ordered as follows: the epiconus followed by the conus medullaris and cauda equina. The narrowest levels were the epiconus in 22 patients, conus medullaris in 37 patients, and cauda equina in 25 patients. On admission, significantly more patients had a narrowed epiconus of Frankel grades A-C than a narrowed cauda equina. At the final follow-up, there were no significant differences in neurological recovery among those with epiconus, conus medullaris, or cauda equina syndrome. Anatomically classifying the narrowest lesion is useful for clarifying the differences and similarities among these three syndromes. en-copyright= kn-copyright= en-aut-name=HatakeyamaYuji en-aut-sei=Hatakeyama en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HongoMichio en-aut-sei=Hongo en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KidoTadato en-aut-sei=Kido en-aut-mei=Tadato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UrayamaMasakazu en-aut-sei=Urayama en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KasukawaYuji en-aut-sei=Kasukawa en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SasakiHiroshi en-aut-sei=Sasaki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AizawaToshiaki en-aut-sei=Aizawa en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KudoDaisuke en-aut-sei=Kudo en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KimuraRyota en-aut-sei=Kimura en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OnoYuichi en-aut-sei=Ono en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KasamaFumihito en-aut-sei=Kasama en-aut-mei=Fumihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MiyakoshiNaohisa en-aut-sei=Miyakoshi en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Akita Red Cross Hospital kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Akita Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Ogachi Central Hospital kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Noshiro Kousei Medical Center kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Kitaakita Municipal Hospital kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Akita Red Cross Hospital kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Akita University Graduate School of Medicine kn-affil= en-keyword=thoracolumbar spinal injury kn-keyword=thoracolumbar spinal injury en-keyword=terminal end of spinal cord kn-keyword=terminal end of spinal cord en-keyword=conus medullaris kn-keyword=conus medullaris en-keyword=epiconus syndrome kn-keyword=epiconus syndrome en-keyword=cauda equina syndrome kn-keyword=cauda equina syndrome END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=491 end-page=497 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Participation in the Setouchi Triennale and the Health of Residents in Naoshima: A Cross-Sectional Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Arts festivals have become increasingly popular in various parts of Japan in recent years. The purpose of this study was to investigate the relationships between arts festival activities participation at the Setouchi Triennale and the health of residents in the town of Naoshima. This was a cross-sectional study. Questionnaires were distributed to all residents of Naoshima who were 20 years old or older (n=2,588). We analyzed responses from 708 people. The associations between arts festival activities participation and health (measured by self-rated health) were analyzed using logistic regression analysis as the primary outcome. Kessler’s psychological distress scale scores were also analyzed in the same manner as the primary outcome. The participating group had an adjusted odds ratio of 1.86 (95% confidence interval: 1.03-3.33) for higher self-rated health compared with those who did not participate. Kessler’s psychological distress scale results showed that the participating group had an adjusted odds ratio of 3.23 (95% confidence interval: 1.19-8.81) for lower psychological distress compared with those who did not participate. In conclusion, arts festival activities participation was associated with higher self-rated health and lower psychological distress. However, caution must be taken in regard to generalizability and causality when interpreting these results. en-copyright= kn-copyright= en-aut-name=HabuHiroshi en-aut-sei=Habu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyajiChikara en-aut-sei=Miyaji en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AooKen en-aut-sei=Aoo en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishitaYosuke en-aut-sei=Nishita en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsuriMasao en-aut-sei=Tsuri en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Economics, Musashi University kn-affil= affil-num=8 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=art kn-keyword=art en-keyword=arts in public health kn-keyword=arts in public health en-keyword=arts festival kn-keyword=arts festival en-keyword=self-rated health kn-keyword=self-rated health en-keyword=Setouchi Triennale kn-keyword=Setouchi Triennale END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=443 end-page=449 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Does Participation in the Setouchi Triennale Foster Social Capital? : A Cross-Sectional Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study examined whether participation in an art project was associated with higher social capital (SC). We conducted a questionnaire survey from November 2021 to March 2022 among residents aged 20 years or older of Naoshima, an island in Kagawa Prefecture, Japan. Before the survey, the Setouchi Triennale had been held on Naoshima four times, starting in 2010. We calculated propensity scores for Triennale participation and performed propensity score matching. We then compared cognitive and structural SC by Triennale participation and found significant differences, respectively. We adopted a conditional ordered logistic regression analysis with propensity score matching for cognitive or structural SC, and found adjusted odd ratios of 2.913 (95%CI, 1.846-4.596) for cognitive SC and 4.535 (95%CI, 2.839-7.244) for structural SC. Our findings suggest that Triennale participation enhanced the cognitive aspect of SC while also building structural SC. en-copyright= kn-copyright= en-aut-name=MiyajiChikara en-aut-sei=Miyaji en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HabuHiroshi en-aut-sei=Habu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AooKen en-aut-sei=Aoo en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishitaYosuke en-aut-sei=Nishita en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsuriMasao en-aut-sei=Tsuri en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Economics, Musashi University kn-affil= affil-num=8 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=social capital kn-keyword=social capital en-keyword=art project kn-keyword=art project en-keyword=propensity score matching kn-keyword=propensity score matching END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=8 article-no= start-page=6039 end-page=6055 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of a Vitamin-D Receptor Antagonist, MeTC7, which Inhibits the Growth of Xenograft and Transgenic Tumors In Vivo en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vitamin-D receptor (VDR) mRNA is overexpressed in neuroblastoma and carcinomas of lung, pancreas, and ovaries and predicts poor prognoses. VDR antagonists may be able to inhibit tumors that overexpress VDR. However, the current antagonists are arduous to synthesize and are only partial antagonists, limiting their use. Here, we show that the VDR antagonist MeTC7 (5), which can be synthesized from 7-dehydrocholesterol (6) in two steps, inhibits VDR selectively, suppresses the viability of cancer cell-lines, and reduces the growth of the spontaneous transgenic TH-MYCN neuroblastoma and xenografts in vivo. The VDR selectivity of 5 against RXRα and PPAR-γ was confirmed, and docking studies using VDR-LBD indicated that 5 induces major changes in the binding motifs, which potentially result in VDR antagonistic effects. These data highlight the therapeutic benefits of targeting VDR for the treatment of malignancies and demonstrate the creation of selective VDR antagonists that are easy to synthesize. en-copyright= kn-copyright= en-aut-name=KhazanNegar en-aut-sei=Khazan en-aut-mei=Negar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimKyu Kwang en-aut-sei=Kim en-aut-mei=Kyu Kwang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HansenJeanne N. en-aut-sei=Hansen en-aut-mei=Jeanne N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SinghNiloy A. en-aut-sei=Singh en-aut-mei=Niloy A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MooreTaylor en-aut-sei=Moore en-aut-mei=Taylor kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SnyderCameron W. A. en-aut-sei=Snyder en-aut-mei=Cameron W. A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PanditaRavina en-aut-sei=Pandita en-aut-mei=Ravina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=StrawdermanMyla en-aut-sei=Strawderman en-aut-mei=Myla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiharaMichiko en-aut-sei=Fujihara en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakamuraYuta en-aut-sei=Takamura en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=JianYe en-aut-sei=Jian en-aut-mei=Ye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=BattagliaNicholas en-aut-sei=Battaglia en-aut-mei=Nicholas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YanoNaohiro en-aut-sei=Yano en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TeramotoYuki en-aut-sei=Teramoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArnoldLeggy A. en-aut-sei=Arnold en-aut-mei=Leggy A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HopsonRussell en-aut-sei=Hopson en-aut-mei=Russell kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KishorKeshav en-aut-sei=Kishor en-aut-mei=Keshav kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NayakSneha en-aut-sei=Nayak en-aut-mei=Sneha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OjhaDebasmita en-aut-sei=Ojha en-aut-mei=Debasmita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SharonAshoke en-aut-sei=Sharon en-aut-mei=Ashoke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AshtonJohn M. en-aut-sei=Ashton en-aut-mei=John M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=WangJian en-aut-sei=Wang en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MilanoMichael T. en-aut-sei=Milano en-aut-mei=Michael T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MiyamotoHiroshi en-aut-sei=Miyamoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=LinehanDavid C. en-aut-sei=Linehan en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=GerberScott A. en-aut-sei=Gerber en-aut-mei=Scott A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KawarNada en-aut-sei=Kawar en-aut-mei=Nada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=SinghAjay P. en-aut-sei=Singh en-aut-mei=Ajay P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=TabdanovErdem D. en-aut-sei=Tabdanov en-aut-mei=Erdem D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=DokholyanNikolay V. en-aut-sei=Dokholyan en-aut-mei=Nikolay V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=KakutaHiroki en-aut-sei=Kakuta en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=JurutkaPeter W. en-aut-sei=Jurutka en-aut-mei=Peter W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=SchorNina F. en-aut-sei=Schor en-aut-mei=Nina F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=Rowswell-TurnerRachael B. en-aut-sei=Rowswell-Turner en-aut-mei=Rachael B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=SinghRakesh K. en-aut-sei=Singh en-aut-mei=Rakesh K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=MooreRichard G. en-aut-sei=Moore en-aut-mei=Richard G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= affil-num=1 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=2 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=3 en-affil=Department of Pediatrics, University of Rochester Medical Center kn-affil= affil-num=4 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=5 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=6 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=7 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=8 en-affil=Department of Biostatistics and Computational Biology, University of Rochester Medical Center kn-affil= affil-num=9 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center kn-affil= affil-num=12 en-affil=Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center kn-affil= affil-num=13 en-affil=Department of Surgery, Division of Surgical Research, Rhode Island Hospital, Alpert Medical School of Brown University kn-affil= affil-num=14 en-affil=Department of Pathology and Laboratory Medicine, University of Rochester Medical Center kn-affil= affil-num=15 en-affil=Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee kn-affil= affil-num=16 en-affil=Department of Chemistry, Brown University kn-affil= affil-num=17 en-affil=Department of Chemistry, Birla Institute of Technology kn-affil= affil-num=18 en-affil=Department of Chemistry, Birla Institute of Technology kn-affil= affil-num=19 en-affil=Department of Chemistry, Birla Institute of Technology kn-affil= affil-num=20 en-affil=Department of Chemistry, Birla Institute of Technology kn-affil= affil-num=21 en-affil=Genomics Core Facility, Wilmot Cancer Center, University of Rochester Medical Center kn-affil= affil-num=22 en-affil=Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University kn-affil= affil-num=23 en-affil=Department of Radiation Oncology, University of Rochester Medical Center kn-affil= affil-num=24 en-affil=Department of Pathology and Laboratory Medicine, University of Rochester Medical Center kn-affil= affil-num=25 en-affil=Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center kn-affil= affil-num=26 en-affil=Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center kn-affil= affil-num=27 en-affil=Center for Breast Health and Gynecologic Oncology, Mercy Medical Center kn-affil= affil-num=28 en-affil=Rutgers, The State University of New Jersey kn-affil= affil-num=29 en-affil=CytoMechanobiology Laboratory, Department of Pharmacology, Penn State College of Medicine, Pennsylvania State University kn-affil= affil-num=30 en-affil=Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University kn-affil= affil-num=31 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=32 en-affil=School of Mathematical and Natural Sciences, Arizona State University, Health Futures Center kn-affil= affil-num=33 en-affil=Departments of Pediatrics, Neurology, and Neuroscience, University of Rochester Medical Center kn-affil= affil-num=34 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=35 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= affil-num=36 en-affil=Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center kn-affil= END start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue=1 article-no= start-page=18 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Data-driven model of the local wind field over two small lakes in Jyväskylä, Finland en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study presents a data-driven model of the local wind field over two small lakes in Jyväskylä, Finland. Five temporary monitoring stations installed during the summers of 2015 and 2016 observed wind speed/direction around the two lakes. In addition, an official meteorological station located 15 km north of the lakes is permanently available. Our goal was to develop a model that could evaluate wind speed and direction over the two lakes using only data from the permanent station. Statistical analysis for the spatio-temporal wind data revealed that (1) local wind speed is correlated with the elevation and its cyclic pattern is identical to that of the official-station data, and (2) the local wind direction field is spatially homogeneous and is strongly correlated with the official-station data. Based on these results, we built two regression models for estimating spatial distribution of local wind speed and directions based on the digital elevation model (DEM) and official-station data. We compared the predicted wind speeds/directions by the proposed model with the corresponding observation data and a numerical result for model validation. We found that the proposed model could effectively simulate heterogeneous local wind fields and considers uncertainty of estimates. en-copyright= kn-copyright= en-aut-name=ShukuTakayuki en-aut-sei=Shuku en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RopponenJanne en-aut-sei=Ropponen en-aut-mei=Janne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JuntunenJanne en-aut-sei=Juntunen en-aut-mei=Janne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuitoHiroshi en-aut-sei=Suito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Finnish Environment Institute SYKE, Jyväskylä Office kn-affil= affil-num=3 en-affil=Finnish Environment Institute SYKE, Jyväskylä Office kn-affil= affil-num=4 en-affil=Advanced Institute for Materials Research (AIMR), Tohoku University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=3 article-no= start-page=e12286 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of malnutrition on prognosis in patients with pulmonary arterial hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary arterial hypertension is a life-threatening disease that coexists with right heart failure. We evaluated the relationship between malnutrition and prognosis in patients with pulmonary arterial hypertension, as malnutrition is known as a prognosis determinant in chronic heart failure. We retrospectively reviewed data of patients with pulmonary arterial hypertension before treatment. The Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Controlling Nutritional Status scores on the day of diagnosis were calculated to assess the nutritional status. Clinical endpoints were defined as composite outcomes of all-cause death or lung transplantation. Eighty patients were enrolled (mean age, 50 years; 23 men). The mean pulmonary arterial pressure was 47 ± 19 mmHg, Geriatric Nutritional Risk Index was 99.9 ± 12.0, and Prognostic Nutritional Index was 46.3 ± 10.0. The median Controlling Nutritional Status score was 2 (1–4). During the median 5.5-year follow-up period, 28 composite events occurred. Kaplan-Meier analysis demonstrated significant differences in the incidence of clinical endpoints between groups divided by each median Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Controlling Nutritional Status score (p = 0.007, 0.039, and 0.010, respectively). In multivariate Cox regression analysis, clinical endpoints were significantly associated with Geriatric Nutritional Risk Index (hazard ratio: 0.953, 95% confidence interval: 0.918–0.990), Prognostic Nutritional Index (hazard ratio: 0.942, 95% confidence interval: 0.892–0.996), and Controlling Nutritional Status score (hazard ratio: 1.230, 95% confidence interval: 1.056–1.433) after adjustment for factors associated in univariate Cox regression analysis. Malnutrition at diagnosis is a useful prognostic predictor for patients with pulmonary arterial hypertension. en-copyright= kn-copyright= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Controlling Nutritional Status score kn-keyword=Controlling Nutritional Status score en-keyword=Geriatric Nutritional Risk Index kn-keyword=Geriatric Nutritional Risk Index en-keyword=nutritional status kn-keyword=nutritional status en-keyword=Prognostic Nutritional Index kn-keyword=Prognostic Nutritional Index END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=e000772 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220927 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of one-point glucocorticoid-free status with chronic damage and disease duration in systemic lupus erythematosus: a cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective　It is still unclear how glucocorticoids (GCs) affect the long-term clinical course of patients with SLE. The objective of this study is to explore the factors associated with GC-free treatment status.
Methods　Using data from the lupus registry of nationwide institutions, GC dose at registration was compared between short, middle and long disease durations of <5, 5–20 and ≥20 years, respectively. After excluding patients who never used GC, we evaluated the relationship between GC-free status and chronic damage using Systemic Lupus International Collaborating Clinics Damage Index.
Results　GC doses at enrolment of the 1019 patients were as follows: GC-free in 101 (10%); 0 Conclusion　Even in the patients with long disease duration, one-point GC-free treatment status might be related to no chronic damage accrual. en-copyright= kn-copyright= en-aut-name=SadaKen-ei en-aut-sei=Sada en-aut-mei=Ken-ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatayamaYu en-aut-sei=Katayama en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsanoYosuke en-aut-sei=Asano en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayashiKeigo en-aut-sei=Hayashi en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhashiKeiji en-aut-sei=Ohashi en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Takano-NarazakiMariko en-aut-sei=Takano-Narazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshimiRyusuke en-aut-sei=Yoshimi en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShimojimaYasuhiro en-aut-sei=Shimojima en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhnoShigeru en-aut-sei=Ohno en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KajiyamaHiroshi en-aut-sei=Kajiyama en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IchinoseKunihiro en-aut-sei=Ichinose en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SatoShuzo en-aut-sei=Sato en-aut-mei=Shuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FujiwaraMichio en-aut-sei=Fujiwara en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YajimaNobuyuki en-aut-sei=Yajima en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine kn-affil= affil-num=13 en-affil=Center for Rheumatic Diseases, Yokohama City University Medical Center kn-affil= affil-num=14 en-affil=Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University kn-affil= affil-num=15 en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=16 en-affil=Department of Rheumatology, Fukushima Medical University School of Medicine kn-affil= affil-num=17 en-affil=Department of Rheumatology, Yokohama Rosai Hospital kn-affil= affil-num=18 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= en-keyword=systemic lupus erythematosus kn-keyword=systemic lupus erythematosus en-keyword=glucocorticoids kn-keyword=glucocorticoids en-keyword=outcome assessment kn-keyword=outcome assessment en-keyword=health care kn-keyword=health care en-keyword=epidemiology kn-keyword=epidemiology END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=1261330 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230907 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established.
Methods: In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as 125I, 18F-tetrafluoroborate (TFB), and 99mTc-pertechnetate (99mTcO4−), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs.
Results: To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by 99mTcO4− single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of 125I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using 99mTcO4− SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells.
Discussion: Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions. en-copyright= kn-copyright= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NoseNaoko en-aut-sei=Nose en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IidaToshihiro en-aut-sei=Iida en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkazawaKaoru en-aut-sei=Akazawa en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KannoTakayuki en-aut-sei=Kanno en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimotoYuki en-aut-sei=Fujimoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkehiMasaru en-aut-sei=Akehi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Okayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Okayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=sodium/iodide symporter kn-keyword=sodium/iodide symporter en-keyword=human induced pluripotent stem cell-derived cardiomyocytes kn-keyword=human induced pluripotent stem cell-derived cardiomyocytes en-keyword=single photon emission computed tomography kn-keyword=single photon emission computed tomography en-keyword=cell-based therapy kn-keyword=cell-based therapy en-keyword=in vivo imaging kn-keyword=in vivo imaging END start-ver=1.4 cd-journal=joma no-vol=183 cd-vols= no-issue= article-no= start-page=29 end-page=37 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The Early Writings of Sir William Temple: Romances kn-title=サー・ウィリアム・テンプルの初期著作 ― ロマンス ― en-subtitle= kn-subtitle= en-abstract= kn-abstract=　サー・ウィリアム・テンプルは，グランド・ツアーの滞在先で９編のロマンスを書いている。テンプル最初期の著作である。いずれも短編で，フランソワ・ド・ロセの『現代悲劇物語』の翻案である。そのうち，現在読むことができるのは５編のみである。文学作品として見た場合，物語のプロットや人物造形が単純かつ類型的で，多くの欠点が目立つ。しかしたとえ稚拙なものであろうとも，それら若書きの作品の中に，創作していたときのテンプルの内面をのぞき見ることができる。そこには，恋人ドロシー・オズボーンとの仲を引き裂かれ，大陸の旅先で悶々とした日々を送っていたテンプルのやり場のない感情が込められているのである。本稿は，22 歳前後に書かれた散文ロマンスをテンプルの伝記の中に位置づけ，それと関連づけながら読む必要があることを明らかにした。 en-copyright= kn-copyright= en-aut-name=KISHIMOTOHiroshi en-aut-sei=KISHIMOTO en-aut-mei=Hiroshi kn-aut-name=岸本広司 kn-aut-sei=岸本 kn-aut-mei=広司 aut-affil-num=1 ORCID= affil-num=1 en-affil=Faculty of Education, Okayama University kn-affil=岡山大学学術研究院教育学域 en-keyword=サー・ウィリアム・テンプル kn-keyword=サー・ウィリアム・テンプル en-keyword=ドロシー・オズボーン kn-keyword=ドロシー・オズボーン en-keyword=ロマンス kn-keyword=ロマンス en-keyword=翻案 kn-keyword=翻案 END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=24 article-no= start-page=eabo2658 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amphotericin B, an antifungal drug with a long history of use, forms fungicidal ion-permeable channels across cell membranes. Using solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we experimentally elucidated the three-dimensional structure of the molecular assemblies formed by this drug in membranes in the presence of the fungal sterol ergosterol. A stable assembly consisting of seven drug molecules was observed to form an ion conductive channel. The structure is somewhat similar to the upper half of the barrel-stave model proposed in the 1970s but substantially different in the number of molecules and in their arrangement. The present structure explains many previous findings, including structure-activity relationships of the drug, which will be useful for improving drug efficacy and reducing adverse effects. en-copyright= kn-copyright= en-aut-name=UmegawaYuichi en-aut-sei=Umegawa en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoTomoya en-aut-sei=Yamamoto en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DixitMayank en-aut-sei=Dixit en-aut-mei=Mayank kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FunahashiKosuke en-aut-sei=Funahashi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SeoSangjae en-aut-sei=Seo en-aut-mei=Sangjae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakagawaYasuo en-aut-sei=Nakagawa en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzukiTaiga en-aut-sei=Suzuki en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuokaShigeru en-aut-sei=Matsuoka en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsuchikawaHiroshi en-aut-sei=Tsuchikawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HanashimaShinya en-aut-sei=Hanashima en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OishiTohru en-aut-sei=Oishi en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsumoriNobuaki en-aut-sei=Matsumori en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShinodaWataru en-aut-sei=Shinoda en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MurataMichio en-aut-sei=Murata en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=2 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=3 en-affil=Department of Materials Chemistry, Graduate School of Engineering, Nagoya University kn-affil= affil-num=4 en-affil=Department of Materials Chemistry, Graduate School of Engineering, Nagoya University kn-affil= affil-num=5 en-affil=Department of Materials Chemistry, Graduate School of Engineering, Nagoya University kn-affil= affil-num=6 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=7 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=8 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=9 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=10 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=11 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=12 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=13 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=14 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=18 article-no= start-page=2059 end-page=2066 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Incremental prognostic value of non-alcoholic fatty liver disease over coronary computed tomography angiography findings in patients with suspected coronary artery disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims　This study aimed to investigate additional risk stratification benefits of hepatic steatosis (HS) concurrently assessed during coronary computed tomography angiography (CTA) in a large patient cohort with suspected stable coronary artery disease (CAD).
Methods and results　In this prospective study, 1148 Japanese outpatients without a history of CAD who underwent coronary CTA for suspected stable CAD (mean age 64 ± 14 years) were included. HS, defined on CT as a hepatic-to-spleen attenuation ratio of <1.0, was examined just before the evaluation of adverse CTA findings, defined as obstructive and/or high-risk plaque. The major adverse cardiac events (MACE) were the composite of cardiac death, acute coronary syndrome, and late revascularization. The incremental predictive value of HS was evaluated using the global χ2 test and C-statistic. HS was identified in 247 (22%) patients. During a median follow-up of 3.9 years, MACE was observed in 40 (3.5%) patients. HS was significantly associated with MACE in a model that included adverse CTA findings (hazard ratio 4.01, 95% confidence interval 2.12–7.59, P < 0.001). By adding HS to the Framingham risk score and adverse CTA findings, the global χ2 score and C-statistic significantly increased from 29.0 to 49.5 (P < 0.001) and 0.74 to 0.81 (P = 0.026), respectively. In subgroup analyses in patients with diabetes mellitus and metabolic syndrome, HS had significant additive predictive value for MACE over the Framingham risk score and adverse CTA findings.
Conclusion　In patients with suspected stable CAD, concurrent evaluation of HS during coronary CTA enables more accurate detection of patients at higher risk of MACE. en-copyright= kn-copyright= en-aut-name=IchikawaKeishi en-aut-sei=Ichikawa en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TodaHironobu en-aut-sei=Toda en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Coronary artery disease kn-keyword=Coronary artery disease en-keyword=Computed tomography angiography kn-keyword=Computed tomography angiography en-keyword=Atherosclerotic plaque kn-keyword=Atherosclerotic plaque en-keyword=Risk assessment kn-keyword=Risk assessment en-keyword=Hepatic steatosis kn-keyword=Hepatic steatosis END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=3 article-no= start-page=423 end-page=431 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The number of circulating CD34-positive cells is an independent predictor of coronary artery calcification progression: Sub-analysis of a prospective multicenter study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Decreases in circulating CD34-positive cells are associated with increases in cardiovascular events. We investigated the association between the number of CD34-positive cells and the progression of coronary artery calcification (CAC), a marker of atherosclerosis, in patients with hypercholesteremia under statin therapy in a sub-analysis of a multicenter study.
Methods: In the principal study, patients with CAC scores of 1–999 were treated with pitavastatin. Measurement of CAC by non-enhanced computed tomography and a blood test were performed at baseline and at 1-year follow-up. Patients were divided into two groups: CAC progression (change in CAC score > 0) and non-progression. The number of circulating CD34-positive cells was counted using flow cytometry.
Results: A total of 156 patients (mean age 67 years, 55% men) were included in this sub-analysis. CD34 positive cell numbers at baseline as a continuous variable was inversely correlated with annual change in the log-transformed CAC score (r = –0.19, p = 0.02). When patients were divided into high and low CD34 groups based on the median value of 0.8 cells/μL, the adjusted change in CAC score in the low-CD34 group was significantly greater than that in the high-CD34 group (54.2% vs. 20.8%, respectively, p = 0.04). In multiple logistic analysis, a low CD34-positive cell number was an independent predictor of CAC progression, with an odds ratio of 2.88 (95% confidence interval 1.28–6.49, p = 0.01).
Conclusions: Low numbers of CD34-positive cells are associated with CAC progression in patients with hypercholesterolemia under statin therapy. The number of CD34-positive cells may help to identify patients at increased cardiovascular risk. en-copyright= kn-copyright= en-aut-name=IchikawaKeishi en-aut-sei=Ichikawa en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KohnoKunihisa en-aut-sei=Kohno en-aut-mei=Kunihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KoyamaYasushi en-aut-sei=Koyama en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiology, Sakurabashi Watanabe Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= en-keyword=coronary artery calcification kn-keyword=coronary artery calcification en-keyword=computed tomography kn-keyword=computed tomography en-keyword=endothelial progenitor cells kn-keyword=endothelial progenitor cells en-keyword=hypercholesterolemia kn-keyword=hypercholesterolemia END start-ver=1.4 cd-journal=joma no-vol=263 cd-vols= no-issue= article-no= start-page=133 end-page=166 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230816 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The universal factorial Hall–Littlewood P- and Q-functions en-subtitle= kn-subtitle= en-abstract= kn-abstract=We introduce factorial analogues of the ordinary Hall–Littlewood P- and Q-polynomials, which we call the factorial Hall–Littlewood P- and Q-polynomials. Using the universal formal group law, we further generalize these polynomials to the universal factorial Hall–Littlewood P- and Q-functions. We show that these functions satisfy the vanishing property which the ordinary factorial Schur S-, P-, and Q-polynomials have. By the vanishing property, we derive the Pieri-type formula and a certain generalization of the classical hook formula. We then characterize our functions in terms of Gysin maps from flag bundles in complex cobordism theory. Using this characterization and Gysin formulas for flag bundles, we obtain generating functions for the universal factorial Hall–Littlewood P- and Q-functions. Using our generating functions, we show that our factorial Hall–Littlewood P- and Q-polynomials have a certain cancellation property. Further applications such as Pfaffian formulas for K-theoretic factorial Q-polynomials are also given. en-copyright= kn-copyright= en-aut-name=NakagawaMasaki en-aut-sei=Nakagawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaruseHiroshi en-aut-sei=Naruse en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Education Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Education University of Yamanashi kn-affil= en-keyword=factorial Hall-Littlewood P-and Q-functions kn-keyword=factorial Hall-Littlewood P-and Q-functions en-keyword=generating func-tions kn-keyword=generating func-tions en-keyword=formal group laws kn-keyword=formal group laws en-keyword=complex cobordism theory kn-keyword=complex cobordism theory en-keyword=Gysin formulas kn-keyword=Gysin formulas END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=5 article-no= start-page=e0285273 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC.

Methods
Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more.

Results
We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11).

Conclusion
Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. en-copyright= kn-copyright= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkumuraNorihito en-aut-sei=Okumura en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHiroyuki en-aut-sei=Suzuki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GembaKenichi en-aut-sei=Gemba en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SanoIsao en-aut-sei=Sano en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujinagaTakuji en-aut-sei=Fujinaga en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaMasafumi en-aut-sei=Kataoka en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerazakiYasuhiro en-aut-sei=Terazaki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KataokaKazuhiko en-aut-sei=Kataoka en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KosakaShinji en-aut-sei=Kosaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakamuraHiroshige en-aut-sei=Nakamura en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamashitaYoshinori en-aut-sei=Yamashita en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MoritaSatoshi en-aut-sei=Morita en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MatsuoKeitaro en-aut-sei=Matsuo en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=SakamotoJunichi en-aut-sei=Sakamoto en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Division of Thoracic Surgery, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Chest Surgery, Fukushima Medical University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center kn-affil= affil-num=10 en-affil=Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory S0urgery, Saga-Ken Medical Centre Koseikan kn-affil= affil-num=12 en-affil=Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=13 en-affil=Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=14 en-affil=Department of Thoracic Surgery, Shimane Prefectural Central Hospital kn-affil= affil-num=15 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=16 en-affil=Department of Thoracic Surgery, National Hospital Organization Yamaguchi-Ube Medical Center kn-affil= affil-num=17 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=18 en-affil=Division of General Thoracic Surgery, Tottori University Hospital kn-affil= affil-num=19 en-affil=Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=20 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=22 en-affil=Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine kn-affil= affil-num=23 en-affil=Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute kn-affil= affil-num=24 en-affil=Tokai Central Hospital kn-affil= affil-num=25 en-affil=Department of Thoracic Surgery, Kyoto University Hospital kn-affil= affil-num=26 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=81 cd-vols= no-issue=1 article-no= start-page=58 end-page=67 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220309 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Improvement of anterior disc displacement on the mandibular deviated side after intraoral vertical ramus osteotomy in a patient with facial asymmetry: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: We present the orthognathic treatment of an adult skeletal Class III patient with facial asymmetry, mandibular rightward deviation, and anterior disc displacement without reduction (ADDwoR) at the right temporomandibular joint (TMJ) by intraoral vertical ramus osteotomy (IVRO).
Materials and methods: The patient was a 23-year-old man with complaints of mandibular deviation and crowded lower anterior teeth, resulting in facial asymmetry. The maxillary position was normal with protrusion and rightward deviation of the mandible. There was no cant of the maxilla. He experienced pain in the right TMJ during mastication, and Magnetic resonance imaging (MRI) revealed an ADDwoR on the right side. The patient was diagnosed with Class III malocclusion, skeletal Class III prognathism with mandibular deviation, and ADDwoR on the right side. Orthognathic surgery was proposed for jaw deformity, and IVRO was performed to correct mandibular deviation.
Results: One year and 2 months after treatment onset, IVRO was performed with differential setback: 2 mm on the right and 8 mm on the left side of the mandible. The midline of the lower dentition was rotated by 6 mm to coincide with the facial midline. Symptoms of temporomandibular disorders were not observed post-operatively. Active-treatment period was for 31 months. MRI findings showed improvement in anterior disc displacement on the right side during the post-retention.
Conclusion: In the case of facial asymmetry with anterior disc displacement on the mandibular deviated side, IVRO was suggested to have a potential effect on the positional relationship between the mandibular head and temporomandibular disc. en-copyright= kn-copyright= en-aut-name=UedaHirotaka en-aut-sei=Ueda en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkaNaoki en-aut-sei=Oka en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimoTsuyoshi en-aut-sei=Shimo en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiAkira en-aut-sei=Sasaki en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamashiroTakashi en-aut-sei=Yamashiro en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthodontics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry kn-affil= affil-num=6 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Facial asymmetry kn-keyword=Facial asymmetry en-keyword=mandibular deviation kn-keyword=mandibular deviation en-keyword=anterior disc displacement kn-keyword=anterior disc displacement en-keyword=temporomandibular disorders kn-keyword=temporomandibular disorders en-keyword=intraoral vertical ramus osteotomy kn-keyword=intraoral vertical ramus osteotomy END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue=2 article-no= start-page=92 end-page=94 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Autophagy kn-title=オートファジー en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakeiKohji en-aut-sei=Takei en-aut-mei=Kohji kn-aut-name=竹居孝二 kn-aut-sei=竹居 kn-aut-mei=孝二 aut-affil-num=1 ORCID= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name=山田浩司 kn-aut-sei=山田 kn-aut-mei=浩司 aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Neurosience, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域　生化学 affil-num=2 en-affil=Department of Neurosience, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域　生化学 END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue=2 article-no= start-page=85 end-page=88 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A third step of visual art instruction in medical education : Introduction of visual thinking strategies supported by Okayama Prefectural Museum of Art kn-title=医学における「ビジュアルアート教育」の展開：第３ステップ― 岡山県立美術館の協力による対話型鑑賞の導入― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KimataYoshihiro en-aut-sei=Kimata en-aut-mei=Yoshihiro kn-aut-name=木股敬裕 kn-aut-sei=木股 kn-aut-mei=敬裕 aut-affil-num=1 ORCID= en-aut-name=ObikaMikako en-aut-sei=Obika en-aut-mei=Mikako kn-aut-name=小比賀美香子 kn-aut-sei=小比賀 kn-aut-mei=美香子 aut-affil-num=2 ORCID= en-aut-name=KuboTakuya en-aut-sei=Kubo en-aut-mei=Takuya kn-aut-name=久保卓也 kn-aut-sei=久保 kn-aut-mei=卓也 aut-affil-num=3 ORCID= en-aut-name=OtsukaMasumi en-aut-sei=Otsuka en-aut-mei=Masumi kn-aut-name=大塚益美 kn-aut-sei=大塚 kn-aut-mei=益美 aut-affil-num=4 ORCID= en-aut-name=OkamotoYuko en-aut-sei=Okamoto en-aut-mei=Yuko kn-aut-name=岡本裕子 kn-aut-sei=岡本 kn-aut-mei=裕子 aut-affil-num=5 ORCID= en-aut-name=FukutomiKoh en-aut-sei=Fukutomi en-aut-mei=Koh kn-aut-name=福冨幸 kn-aut-sei=福冨 kn-aut-mei=幸 aut-affil-num=6 ORCID= en-aut-name=MatsumotoHiroshi en-aut-sei=Matsumoto en-aut-mei=Hiroshi kn-aut-name=松本洋 kn-aut-sei=松本 kn-aut-mei=洋 aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil=岡山大学病院　形成再建外科 affil-num=2 en-affil=Department of General Medicine, Okayama University Hospital kn-affil=岡山大学病院　総合内科・総合診療科 affil-num=3 en-affil=Department of Emergency and Critical Care Medicine, Okayama University Hospital kn-affil=岡山大学病院　救命救急科 affil-num=4 en-affil=OTSUKA DESIGN Co., Ltd. kn-affil=株式会社大塚デザイン affil-num=5 en-affil=Okayama Prefectural Museum of Art kn-affil=岡山県立美術館 affil-num=6 en-affil=Okayama Prefectural Museum of Art kn-affil=岡山県立美術館 affil-num=7 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil=岡山大学病院　形成再建外科 END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=15 article-no= start-page=5028 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. Methods: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. Results: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia. Conclusions: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia. en-copyright= kn-copyright= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoMegumi en-aut-sei=Kondo en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishidaMikako en-aut-sei=Nishida en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=glycolysis kn-keyword=glycolysis en-keyword=mitochondrial respiration kn-keyword=mitochondrial respiration en-keyword=pulmonary arterial hypertension kn-keyword=pulmonary arterial hypertension en-keyword=pulmonary artery smooth muscle cells kn-keyword=pulmonary artery smooth muscle cells en-keyword=Seahorse technology kn-keyword=Seahorse technology en-keyword=hypoxia kn-keyword=hypoxia en-keyword=ATP production kn-keyword=ATP production END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=4 article-no= start-page=387 end-page=394 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between Radon Hot Spring Bathing and Health Conditions: A Cross-Sectional Study in Misasa, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=No epidemiological studies have examined the health effects of daily bathing in radon hot springs. In this cross-sectional study, we investigated the associations between radon hot spring bathing and health conditions. The target population was 5,250 adults ≥ 20 years old in the town of Misasa, Japan. We collected information about the participants’ bathing habits and alleviation of a variety of disease symptoms, and their self-rated health (SRH). Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated. In both the adjusted and unadjusted models of hypertension, significant associations between the > 1×/week hot spring bathing and the alleviation of hypertension symptoms were observed compared to the group whose hot spring bathing was <1×/week: adjusted model, OR 5.40 (95%CI: 1.98-14.74); unadjusted model, 3.67 (1.50-8.99) and for gastroenteritis: adjusted model, 9.18 (1.15-72.96); unadjusted model, 7.62 (1.59-36.49). Compared to the no-bathing group, higher SRH was significantly associated with both bathing < 1×/week: unadjusted model, 2.27 (1.53-3.37) and > 1×/week: adjusted model, 1.91 (1.15-3.19). These findings suggest that bathing in radon hot springs is associated with higher SRH and the alleviation of hypertension and gastroenteritis. en-copyright= kn-copyright= en-aut-name=KataokaTakahiro en-aut-sei=Kataoka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HabuHiroshi en-aut-sei=Habu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaAyumi en-aut-sei=Tanaka en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaoeShota en-aut-sei=Naoe en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiKaito en-aut-sei=Murakami en-aut-mei=Kaito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimotoYuki en-aut-sei=Fujimoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YukimineRyohei en-aut-sei=Yukimine en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MitsunobuFumihiro en-aut-sei=Mitsunobu en-aut-mei=Fumihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamaokaKiyonori en-aut-sei=Yamaoka en-aut-mei=Kiyonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Longevity and Social Medicine (Geriatrics), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=radon hot spring kn-keyword=radon hot spring en-keyword=bathing habit kn-keyword=bathing habit en-keyword=self-rated health kn-keyword=self-rated health en-keyword=cross-section study kn-keyword=cross-section study END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=12 article-no= start-page=1927 end-page=1949 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhanced Production of EPA-Derived Anti-Inflammatory Metabolites after Oral Administration of a Novel Self-Emulsifying Highly Purified EPA Ethyl Ester Formulation (MND-2119) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: MND-2119 is a novel once-daily dose self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (EPA-E) and is approved as an antihyperlipidemia agent in Japan. It has improved absorption and achieves higher plasma EPA concentrations at Cmax than conventional EPA-E. In the JELIS trial, concomitant use of EPA-E with statin therapy significantly reduced atherosclerotic cardiovascular disease (ASCVD) risks. As a potential mechanism of action of EPA, endogenous formation of EPA-derived anti-inflammatory metabolites is receiving greater attention. This study aims to investigate the endogenous formation of EPA-derived anti-inflammatory metabolites following single and multiple administrations of MND-2119.
Methods: Healthy adult male subjects were randomly assigned to a nonintervention (control) group, MND-2119 2-g/day group, MND-2119 4-g/day group, or EPA-E 1.8-g/day group for 7 days (N=8 per group). Plasma fatty acids and EPA-derived metabolites were evaluated. Peripheral blood neutrophils were isolated, and the production of EPA-derived metabolites from in vitro stimulated neutrophils was evaluated.
Results: After single and multiple administrations of MND-2119 2 g/day, there were significant increases in plasma EPA concentration, 18-hydroxyeicosapentaenoic acid (18-HEPE), and 17,18-epoxyeicosatetraenoic acid compared with those of EPA-E 1.8 g/day. They were further increased with MND-2119 4 g/day administration. In neutrophils, the EPA concentration in the MND-2119 2-g/day group was significantly higher compared with that in the EPA-E 1.8-g/day group after multiple administration, and 18-HEPE production was positively correlated with EPA concentration. No safety issues were noted.
Conclusions: These results demonstrate that MND-2119 increases the plasma and cellular concentrations of EPA and EPA-derived metabolites to a greater extent than conventional EPA-E formulations. en-copyright= kn-copyright= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaoeSatoko en-aut-sei=Naoe en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WakabayashiHiroyuki en-aut-sei=Wakabayashi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanoTakashi en-aut-sei=Yano en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriTakuya en-aut-sei=Mori en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KandaShingo en-aut-sei=Kanda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AritaMakoto en-aut-sei=Arita en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Medical Affairs Department, Mochida Pharmaceutical Co., Ltd. kn-affil= affil-num=3 en-affil=Medical Affairs Department, Mochida Pharmaceutical Co., Ltd. kn-affil= affil-num=4 en-affil=Medical Affairs Department, Mochida Pharmaceutical Co., Ltd. kn-affil= affil-num=5 en-affil=Clinical Research Department, Mochida Pharmaceutical Co., Ltd. kn-affil= affil-num=6 en-affil=Clinical Development Planning and Management Department, Mochida Pharmaceutical Co., Ltd. kn-affil= affil-num=7 en-affil=Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Eicosapentaenoic acid kn-keyword=Eicosapentaenoic acid en-keyword=MND-2119 kn-keyword=MND-2119 en-keyword=Metablolite kn-keyword=Metablolite en-keyword=Inflammation kn-keyword=Inflammation END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=216 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230620 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Associations of systemic oxygen consumption with age and body temperature under general anesthesia: retrospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background　Body temperature (BT) is thought to have associations with oxygen consumption (VO2). However, there have been few studies in which the association between systemic VO2 and BT in humans was investigated in a wide range of BTs. The aims of this study were 1) to determine the association between VO2 and age and 2) to determine the association between VO2 and BT.
Methods　This study was a retrospective study of patients who underwent surgery under general anesthesia at a tertiary teaching hospital. VO2 was measured by the Dräger Perseus A500 anesthesia workstation (Dräger Medical, Lubeck, Germany). The associations of VO2 with age and BT were examined using spline regression and multivariable regression analysis with a random effect.
Results　A total of 7,567 cases were included in this study. A linear spline with one knot shows that VO2 was reduced by 2.1 ml/kg/min with one year of age (p < 0.001) among patients less than 18 years of age and that there was no significant change in VO2 among patients 18 years of age or older (estimate: 0.014 ml/kg/min, p = 0.08). VO2 in all bands of BT < 36.0 °C was not significantly different from VO2 in BT > = 36 °C and < 36.5 °C. Multivariable linear regression analysis showed that compared with VO2 in BT > = 36 °C and < 36.5 °C as a reference, VO2 levels were significantly higher by 0.57 ml/kg/min in BT > = 36.5 °C and < 37 °C (p < 0.001), by 1.8 ml/kg/min in BT > = 37 °C and < 37.5 °C (p < 0.001), by 3.6 ml/kg/min in BT > = 37.5 °C and < 38 °C (p < 0.001), by 4.9 ml/kg/min in BT > = 38 °C and < 38.5 °C (p < 0.001), and by 5.7 ml/kg/min in BT > = 38.5 °C (p < 0.001). The associations between VO2 and BT were significantly different among categorized age groups (p = 0.03).
Conclusions　VO2 increases in parallel with increase in body temperature in a hyperthermic state but remains constant in a hypothermic state. Neonates and infants, who have high VO2, may have a large systemic organ response in VO2 to change in BT. en-copyright= kn-copyright= en-aut-name=KimuraSatoshi en-aut-sei=Kimura en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimizuKazuyoshi en-aut-sei=Shimizu en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= en-keyword=Oxygen Consumption kn-keyword=Oxygen Consumption en-keyword=Body Temperature kn-keyword=Body Temperature en-keyword=General Anesthesia kn-keyword=General Anesthesia END start-ver=1.4 cd-journal=joma no-vol=567 cd-vols= no-issue= article-no= start-page=216260 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dual antiplatelet therapy inhibits neutrophil extracellular traps to reduce liver micrometastases of intrahepatic cholangiocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=The involvement of neutrophil extracellular traps (NETs) in cancer metastasis is being clarified, but the relationship between intrahepatic cholangiocarcinoma (iCCA) and NETs remains unclear. The presence of NETs was verified by multiple fluorescence staining in clinically resected specimens of iCCA. Human neutrophils were co-cultured with iCCA cells to observe NET induction and changes in cellular characteristics. Binding of platelets to iCCA cells and its mechanism were also examined, and their effects on NETs were analyzed in vitro and in in vivo mouse models. NETs were present in the tumor periphery of resected iCCAs. NETs promoted the motility and migration ability of iCCA cells in vitro. Although iCCA cells alone had a weak NET-inducing ability, the binding of platelets to iCCA cells via P-selectin promoted NET induction. Based on these results, antiplatelet drugs were applied to these cocultures in vitro and inhibited the binding of platelets to iCCA cells and the induction of NETs. Fluorescently labeled iCCA cells were injected into the spleen of mice, resulting in the formation of liver micrometastases coexisting with platelets and NETs. These mice were treated with dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor, which dramatically reduced micrometastases. These results suggest that potent antiplatelet therapy prevents micrometastases of iCCA cells by inhibiting platelet activation and NET production, and it may contribute to a novel therapeutic strategy. en-copyright= kn-copyright= en-aut-name=YoshimotoMasashi en-aut-sei=Yoshimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KajiokaHiroki en-aut-sei=Kajioka en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniguchiAtsuki en-aut-sei=Taniguchi en-aut-mei=Atsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YagiTomohiko en-aut-sei=Yagi en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NogiShohei en-aut-sei=Nogi en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Aspirin kn-keyword=Aspirin en-keyword=Ticagrelor kn-keyword=Ticagrelor en-keyword=P-selectin kn-keyword=P-selectin en-keyword=Platelet kn-keyword=Platelet en-keyword=Time-lapse imaging kn-keyword=Time-lapse imaging END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue=1 article-no= start-page=77 end-page=87 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Oda, N. “Dentou igaku” ga tsukurareru toki: Betonamu iryou seisaku shi［When “Science of Traditional Medicine” Was Constructed: A History of Medical Policy in Vietnam］（Kyoto University Press, 2022） kn-title=小田なら著『〈伝統医学〉が創られるとき：ベトナム医療政策史』（京都大学学術出版会，2022年） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KinoshitaHiroshi en-aut-sei=Kinoshita en-aut-mei=Hiroshi kn-aut-name=木下広志 kn-aut-sei=木下 kn-aut-mei=広志 aut-affil-num=1 ORCID= en-aut-name=FujiiDaiji en-aut-sei=Fujii en-aut-mei=Daiji kn-aut-name=藤井大児 kn-aut-sei=藤井 kn-aut-mei=大児 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=寿晃整骨院 affil-num=2 en-affil= kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=3 article-no= start-page=657 end-page=666 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Important roles of odontoblast membrane phospholipids in early dentin mineralization en-subtitle= kn-subtitle= en-abstract= kn-abstract=The objective of this study was to first identify the timing and location of early mineralization of mouse first molar, and subsequently, to characterize the nucleation site for mineral formation in dentin from a materials science viewpoint and evaluate the effect of environmental cues (pH) affecting early dentin formation. Early dentin mineralization in mouse first molars began in the buccal central cusp on post-natal day 0 (P0), and was first hypothesized to involve collagen fibers. However, elemental mapping indicated the co-localization of phospholipids with collagen fibers in the early mineralization area. Co-localization of phosphatidylserine and annexin V, a functional protein that binds to plasma membrane phospholipids, indicated that phospholipids in the pre-dentin matrix were derived from the plasma membrane. A 3-dimensional in vitro biomimetic mineralization assay confirmed that phospholipids from the plasma membrane are critical factors initiating mineralization. Additionally, the direct measurement of the tooth germ pH, indicated it to be alkaline. The alkaline environment markedly enhanced the mineralization of cell membrane phospholipids. These results indicate that cell membrane phospholipids are nucleation sites for mineral formation, and could be important materials for bottom-up approaches aiming for rapid and more complex fabrication of dentin-like structures. en-copyright= kn-copyright= en-aut-name=AnadaRisa en-aut-sei=Anada en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University kn-affil= affil-num=4 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=8 article-no= start-page=2955 end-page=2971 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220802 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Method for Estimating Physician Stress Using Wearable Sensor Devices en-subtitle= kn-subtitle= en-abstract= kn-abstract=The idea of Society 5.0 initiative has been proposed to solve various social problems by connecting virtual cyberspace and real physical space through information technology. When applying the idea to improve the work-life balance of physicians in the medical field, we must consider the increased stress owing to their long continuous working hours. Estimating the stress of physicians in their daily lives by the questionnaires is insufficient, because of the difficulty of accurate their activity recalling. By using bio-metric information such as heart rate, physical activity, and sleeping information, it was expected that the daily stress state of physicians with high accuracy. In this paper, we propose a method for estimating physician stress by analyzing bio-metric information acquired by wearing a wearable sensor device. The proposed method estimates the state of stress during daily activities by acquiring data on heart rate variability (HRV) during wakefulness as well as sleep depth during rapid eye movement (REM) and non-REM sleep. Up to seven physicians wore the wearable sensor device for the maximum of eight weeks and the sleep depth and low-/high-frequency (LF/HF) components of HRV were obtained. Our observation showed that physicians' root mean square of successive differences (rMSSDs) were constantly high in their healthy state. Therefore, the decreasing of this index can be used as an indicator of fatigue and stress. In addition, by combining LF/HF components to the rMSSDs, we may estimate the stress state of physicians and find personal stressors. en-copyright= kn-copyright= en-aut-name=ImuraIssei en-aut-sei=Imura en-aut-mei=Issei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GotohYusuke en-aut-sei=Gotoh en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaiKoji en-aut-sei=Sakai en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OharaYu en-aut-sei=Ohara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TazoeJun en-aut-sei=Tazoe en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiuraHiroshi en-aut-sei=Miura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HirotaTatsuya en-aut-sei=Hirota en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchiyamaAkira en-aut-sei=Uchiyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NomuraYoshinari en-aut-sei=Nomura en-aut-mei=Yoshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=4 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=5 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=6 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=7 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=8 en-affil=Graduate School of Information Science and Technology, Osaka University kn-affil= affil-num=9 en-affil=Faculty of Natural Science and Technology, Okayama University kn-affil= en-keyword=heart rate variability kn-keyword=heart rate variability en-keyword=LF/HF kn-keyword=LF/HF en-keyword=Society 5.0 kn-keyword=Society 5.0 en-keyword=stress kn-keyword=stress en-keyword=wearable sensor devices kn-keyword=wearable sensor devices en-keyword=working style kn-keyword=working style END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=10 article-no= start-page=e028706 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Significant Delayed Activation on the Right Ventricular Outflow Tract Represents Complete Right Bundle-Branch Block Pattern in Brugada Syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The appearance of complete right bundle-branch block (CRBBB) in Brugada syndrome (BrS) is associated with an increased risk of ventricular fibrillation. The pathophysiological mechanism of CRBBB in patients with BrS has not been well established. We aimed to clarify the significance of a conduction delay zone associated with arrhythmias on CRBBB using body surface mapping in patients with BrS.
Methods and Results: Body surface mapping was recorded in 11 patients with BrS and 8 control patients both with CRBBB. CRBBB in control patients was transiently exhibited by unintentional catheter manipulation (proximal RBBB). Ventricular activation time maps were constructed for both of the groups. We divided the anterior chest into 4 areas (inferolateral right ventricle [RV], RV outflow tract [RVOT], intraventricular septum, and left ventricle) and compared activation patterns between the 2 groups. Excitation propagated to the RV from the left ventricle through the intraventricular septum with activation delay in the entire RV in the control group (proximal RBBB pattern). In 7 patients with BrS, excitation propagated from the inferolateral RV to the RVOT with significant regional activation delay. The remaining 4 patients with BrS showed a proximal RBBB pattern with the RVOT activation delay. The ventricular activation time in the inferolateral RV was significantly shorter in patients with BrS without a proximal RBBB pattern than in control patients.
Conclusions: The CRBBB morphology in patients with BrS consisted of 2 mechanisms: (1) significantly delayed conduction in the RVOT and (2) proximal RBBB with RVOT conduction delay. Significant RVOT conduction delay without proximal RBBB resulted in CRBBB morphology in patients with BrS. en-copyright= kn-copyright= en-aut-name=MorimotoYoshimasa en-aut-sei=Morimoto en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizunoTomofumi en-aut-sei=Mizuno en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasudaTakuro en-aut-sei=Masuda en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UeokaAkira en-aut-sei=Ueoka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AsadaSaori en-aut-sei=Asada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawadaSatoshi en-aut-sei=Kawada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Therapeutics , Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cardiovascular Therapeutics , Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= en-keyword=activation pattern kn-keyword=activation pattern en-keyword=body surface map kn-keyword=body surface map en-keyword=Brugada syndrome kn-keyword=Brugada syndrome en-keyword=complete right bundle-branch block kn-keyword=complete right bundle-branch block END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=12 article-no= start-page=11213 end-page=11219 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230317 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of Pipetteless Paper-Based Analytical Devices with a Volume Gauge en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this work, we propose a new design for paper based analytical devices (PADs) that eliminate the need to use a micropipette for sample introduction. With this design, a PAD is equipped with a distance-based detection channel that is connected to a storage channel that indicates the volume of a sample introduced into the PAD. The analyte in the sample solution reacts with a colorimetric reagent deposited into the distance-based detection channel as the sample solution flows into the storage channel where the volume is measured. The ratio of the lengths of the detection channel and that of the storage channel (D/S ratio) are constant for a sample containing a certain concentration, which is independent of the introduced volume. Therefore, the PADs permit volume-independent quantification using a dropper instead of a micropipette because the length of the storage channel plays the role of a volume gauge to estimate the introduced sample volume. In this study, the D/S ratios obtained with a dropper were comparable to those obtained with a micropipette, which confirmed that precise volume control is unnecessary for this PAD system. The proposed PADs were applied to the determinations of iron and bovine serum albumin using bathophenanthroline and tetrabromophenol blue as colorimetric reagents, respectively. The calibration curves showed good linear relationships with coefficients of 0.989 for iron and 0.994 for bovine serum albumin, respectively. en-copyright= kn-copyright= en-aut-name=DanchanaKaewta en-aut-sei=Danchana en-aut-mei=Kaewta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwasakiHiroshi en-aut-sei=Iwasaki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ThayawutthikunYada en-aut-sei=Thayawutthikun en-aut-mei=Yada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaetearPhoonthawee en-aut-sei=Saetear en-aut-mei=Phoonthawee kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanetaTakashi en-aut-sei=Kaneta en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=3 en-affil=Flow Innovation-Research for Science and Technology Laboratories (FIRST Labs), Mahidol University kn-affil= affil-num=4 en-affil=Flow Innovation-Research for Science and Technology Laboratories (FIRST Labs), Mahidol University kn-affil= affil-num=5 en-affil=Department of Chemistry, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=4 article-no= start-page=e1088 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=2023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Decreased expression of hyaluronan synthase and loss of hyaluronan-rich cells in the anterior tibial fascia of the rat model of chemotherapy-induced peripheral neuropathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Previous studies on chemotherapy-induced peripheral neuropathy (CIPN) have focused on neuronal damage. Although some studies have revealed that the fascia is an important sensory organ, currently, we do not know about chemotherapy drug-induced fascial dysfunction.
Objectives: This study aimed to explore the fascia as a nonneural cause of mechanical hypersensitivity in CIPN by investigating the expression of hyaluronic acid synthase (HAS) and histology of the fascia in an animal model of CIPN.
Methods: Rats were intraperitoneally administered with vincristine (VCR). Mechanical hypersensitivities of the hind paw and the anterior tibial muscle were assessed. The expression of HAS mRNA in the fascia of the anterior tibial muscles was quantitated using reverse transcription polymerase chain reaction. Immunohistochemistry was also performed for HAS2, hyaluronic acid-binding protein, and S100A4 in the fascia.
Results: Vincristine administration significantly decreased mechanical withdrawal thresholds in the hind paw and the anterior tibial muscle after day 3. Quantitative polymerase chain reaction showed significant downregulation of HAS mRNAs in the fascia of VCR-treated rats. Immunohistochemical analysis showed that the number of cells with strong HAS2 immunoreactivity, classified as fasciacytes by morphology and colocalized marker S100A4, decreased significantly in the VCR group.
Conclusion:Hyaluronic acid plays a critical role in somatic pain sensation. Damaged fascia could be a possible cause of musculoskeletal pain in patients with CIPN. This study suggests that fascia is a nonneural cause and novel therapeutic target for chemotherapy-induced "peripheral neuropathy." en-copyright= kn-copyright= en-aut-name=WangRuilin en-aut-sei=Wang en-aut-mei=Ruilin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaYoshikazu en-aut-sei=Matsuoka en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SueNobutaka en-aut-sei=Sue en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakatsukaKosuke en-aut-sei=Nakatsuka en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuboiChika en-aut-sei=Tsuboi en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Chemotherapy-induced peripheral neuropathy kn-keyword=Chemotherapy-induced peripheral neuropathy en-keyword=Fascia kn-keyword=Fascia en-keyword=Fasciacyte kn-keyword=Fasciacyte en-keyword=Hyaluronic acid kn-keyword=Hyaluronic acid en-keyword=Musculoskeletal pain kn-keyword=Musculoskeletal pain en-keyword=Neuropathic pain kn-keyword=Neuropathic pain END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=2078 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ADAR1 is a promising risk stratification biomarker of remnant liver recurrence after hepatic metastasectomy for colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy. en-copyright= kn-copyright= en-aut-name=HataNanako en-aut-sei=Hata en-aut-mei=Nanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakedaSho en-aut-sei=Takeda en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UmedaHibiki en-aut-sei=Umeda en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KishimotoHiroyuki en-aut-sei=Kishimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MoriYoshiko en-aut-sei=Mori en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=18 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=5 article-no= start-page=101485 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Significance of the comprehensive geriatric assessment in the administration of chemotherapy to older adults with cancer: Recommendations by the Japanese Geriatric Oncology Guideline Committee en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: The number of older patients with cancer is expected to continue to increase owing to the aging population. Recently, the usefulness of geriatric assessment (GA) conducted by multiple staff members from different medical backgrounds has been reported; however, a consensus on the effectiveness of GA has not yet been achieved.
Materials and Methods: We, as the Japanese Geriatric Oncology Guideline Committee for elderly patients with cancer, conducted a literature search of randomized controlled trials published before August 2021 that used GA or comprehensive GA (CGA) as an intervention for patients with cancer undergoing chemotherapy. As the key outcomes for answering the clinical question, we focused on survival benefit, adverse events, and quality of life (QOL). After a systematic review of these studies, the expert panel member developed recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.
Results: For older patients with cancer, GA or CGA is suggested during or before chemotherapy (weakly recommended). Chemotherapy-induced adverse events were significantly reduced by GA/CGA interventions without any adverse effects on survival. Health-related QOL tended to improve with the GA/CGA interventions.
Discussion: Although, in our opinion, GA/CGA does require time and resources, it poses no harm patients. Therefore, we suggest expanding the human resources and educating skills of medical providers for clinical implementation of GA/CGA. en-copyright= kn-copyright= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueDaisuke en-aut-sei=Inoue en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugimotoKen en-aut-sei=Sugimoto en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaChie en-aut-sei=Tanaka en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurofushiKeiko en-aut-sei=Murofushi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkuyamaToru en-aut-sei=Okuyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanukiShigeaki en-aut-sei=Watanuki en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ImamuraChiyo K. en-aut-sei=Imamura en-aut-mei=Chiyo K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakaiDaisuke en-aut-sei=Sakai en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakuraiNaomi en-aut-sei=Sakurai en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WatanabeKiyotaka en-aut-sei=Watanabe en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TamuraKazuo en-aut-sei=Tamura en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SaekiToshiaki en-aut-sei=Saeki en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshiguroHiroshi en-aut-sei=Ishiguro en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, University of Fukui kn-affil= affil-num=3 en-affil=Department of General Geriatric Medicine, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=6 en-affil=Department of Psychiatry / Palliative Care Center, Nagoya City University West Medical Center kn-affil= affil-num=7 en-affil=National Center for Global Health and Medicine, National College of Nursing kn-affil= affil-num=8 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=9 en-affil=Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Cancer Solutions Co.,Ltd kn-affil= affil-num=11 en-affil=Division of Medical Oncology, Department of Medicine, School of Medicine, Teikyo University kn-affil= affil-num=12 en-affil=NPO Clinical Hematology/Oncology Treatment Study Group kn-affil= affil-num=13 en-affil=Breast Oncology Service, Saitama Medical University International Medical Center kn-affil= affil-num=14 en-affil=Breast Oncology Service, Saitama Medical University International Medical Center kn-affil= en-keyword=Comprehensive geriatric assessment kn-keyword=Comprehensive geriatric assessment en-keyword=Guideline kn-keyword=Guideline en-keyword=Systematic review kn-keyword=Systematic review END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=9 article-no= start-page=848 end-page=855 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230621 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endoscopic evaluation by the Kyoto classification of gastritis combined with serum anti-Helicobacter pylori antibody testing reliably risk-stratifies subjects in a population-based gastric cancer screening program en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background　We previously demonstrated that the Kyoto classification of gastritis was useful for judging the status of Helicobacter pylori infection in a population-based screening program, and that adding H. pylori antibody test improved its accuracy (UMIN000028629). Here, we tested whether our endoscopic diagnosis of H. pylori infection status reliably estimated gastric cancer risk in the program.
Methods　Data were collected from1345 subjects who underwent endoscopic follow-up 4 years after the end of the registration. We analyzed the association of three diagnostic methods of H. pylori infection with gastric cancer detection: (1) endoscopic diagnosis based on the Kyoto classification of gastritis; (2) serum diagnosis according to the ABC method (H. pylori antibody and pepsinogen I and II); and (3) endoscopic diagnosis together with H. pylori antibody test.
Results　During the follow-up, 19 cases of gastric cancer were detected. By Kaplan–Meier analysis, the detection rates of cancer were significantly higher in the past or current H. pylori infection groups than in the never-infected group with all 3 methods. By the Cox proportional hazards model, the hazard ratio for cancer detection was highest in evaluation with the combined endoscopic diagnosis and the antibody test (method 3; hazard ratio 22.6, 95% confidence interval 2.99–171) among the three methods (the endoscopic diagnosis (method 1); 11.3, 2.58–49.8, and the ABC method (method 2); 7.52, 2.49–22.7).
Conclusions　Endoscopic evaluation of H. pylori status with the Kyoto classification of gastritis, especially combined with serum anti-Helicobacter pylori antibody testing, reliably risk-stratified subjects in a population-based gastric cancer screening program. en-copyright= kn-copyright= en-aut-name=HiraiRyosuke en-aut-sei=Hirai en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraiMami en-aut-sei=Hirai en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimodateYuichi en-aut-sei=Shimodate en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MouriHirokazu en-aut-sei=Mouri en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuedaKazuhiro en-aut-sei=Matsueda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoHiroshi en-aut-sei=Yamamoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MizunoMotowo en-aut-sei=Mizuno en-aut-mei=Motowo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= en-keyword=Cancer screening kn-keyword=Cancer screening en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=Helicobacter pylori kn-keyword=Helicobacter pylori en-keyword=Gastrointestinal endoscopy kn-keyword=Gastrointestinal endoscopy en-keyword=Atrophic gastritis kn-keyword=Atrophic gastritis END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=11 article-no= start-page=2971 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Conventional Cancer Therapies Can Accelerate Malignant Potential of Cancer Cells by Activating Cancer-Associated Fibroblasts in Esophageal Cancer Models en-subtitle= kn-subtitle= en-abstract= kn-abstract=Esophageal cancer is one of the most aggressive tumors, and the outcome remains poor. One contributing factor is the presence of tumors that are less responsive or have increased malignancy when treated with conventional chemotherapy, radiotherapy, or a combination of these. Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Focusing on conventional cancer therapies, we investigated how CAFs acquire therapeutic resistance and how they affect tumor malignancy. In this study, low-dose chemotherapy or radiotherapy-induced normal fibroblasts showed enhanced activation of CAFs markers, fibroblast activation protein, and α-smooth muscle actin, indicating the acquisition of malignancy in fibroblasts. Furthermore, CAFs activated by radiotherapy induce phenotypic changes in cancer cells, increasing their proliferation, migration, and invasion abilities. In in vivo peritoneal dissemination models, the total number of tumor nodules in the abdominal cavity was significantly increased in the co-inoculation group of cancer cells and resistant fibroblasts compared to that in the co-inoculation group of cancer cells and normal fibroblasts. In conclusion, we demonstrated that conventional cancer therapy causes anti-therapeutic effects via the activation of fibroblasts, resulting in CAFs. It is important to select or combine modalities of esophageal cancer treatment, recognizing that inappropriate radiotherapy and chemotherapy can lead to resistance in CAF-rich tumors. en-copyright= kn-copyright= en-aut-name=KomotoSatoshi en-aut-sei=Komoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoTakuya en-aut-sei=Kato en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiTeruki en-aut-sei=Kobayashi en-aut-mei=Teruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NarusakaToru en-aut-sei=Narusaka en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoHiroaki en-aut-sei=Sato en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatsuraYuki en-aut-sei=Katsura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=cancer-associated fibroblast kn-keyword=cancer-associated fibroblast en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=tumor microenvironment kn-keyword=tumor microenvironment END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=6 article-no= start-page=e7595 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230620 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ANCA-associated vasculitis with scleritis, corneal melt, and perforation rescued by rituximab: Case report and literature review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Key Clinical Message: Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, specifically with myeloperoxidase (MPO)-ANCA, would have a risk for developing corneal melt and perforation abruptly in a short period. It is desirable to have a team of collaboration of rheumatologists and other specialties.
Abstract: An 80-year old man who had been diagnosed 5.5 years previously as ANCA-associated vasculitis by temporal artery biopsy developed corneal melt and perforation with scleritis in both eyes. He underwent successful cataract surgery and retained ambulatory vision with the aid of intravenous rituximab. Two additional patients with similar manifestations were found in the literature. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Hiramatsu‐AsanoSumie en-aut-sei=Hiramatsu‐Asano en-aut-mei=Sumie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SawachikaHiroshi en-aut-sei=Sawachika en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraHirotake en-aut-sei=Nishimura en-aut-mei=Hirotake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Rheumatology, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Rheumatology, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Pathology, Kawasaki Medical School kn-affil= en-keyword=ANCA-associated vasculitis kn-keyword=ANCA-associated vasculitis en-keyword=corneal melt and perforation kn-keyword=corneal melt and perforation en-keyword=rituximab kn-keyword=rituximab en-keyword=scleritis kn-keyword=scleritis en-keyword=temporal artery biopsy kn-keyword=temporal artery biopsy END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=3 article-no= start-page=311 end-page=318 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Femoral Stem Fixation Selection in Hip-Fracture Bipolar Hemiarthroplasties, and Factors Affecting Surgeons’ Confidence in Their Ability to Teach about Cemented Stems: A Questionnaire in a Region of Japan with Super-Aged Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Japan’s hip fracture management guidelines now recommend the use of cemented stems in cases of bone fragility. However, the current stem selection practices in bipolar hemiarthroplasty (BHA) in a super-aging area in Japan remain unclear. This study aimed to examine the stem selection policies, the surgeons’ concerns about cemented stems, and factors affecting their confidence in their ability to coach others on cemented stem procedures. Ninety-four orthopedic surgeons (27 facilities) responded to our web-based questionnaire conducted in January/February 2022. Cementless stem was the first choice of 97.8% of the surgeons; <15% of the respondents expected to increase their use of cemented stems in the future. The cement technique was the greatest concern; almost half of the surgeons described having insufficient experience with cemented stems. The factor that most affected the surgeons’ expertise in using cemented stems is the number of surgeries they had conducted with a cemented stem (multivariable analysis odds ratio 8.42, p=0.001). Greater experience was associated with increased expertise of the surgeons in using cemented stems, with a threshold of 11 cases showing sensitivity of 41.7% and specificity of 98.3% for their confidence to instruct cemented stems. en-copyright= kn-copyright= en-aut-name=MiuraTakanori en-aut-sei=Miura en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KijimaHiroaki en-aut-sei=Kijima en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakoshiNaohisa en-aut-sei=Miyakoshi en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Tazawako Hospital kn-affil= affil-num=2 en-affil=Akita Hip Research Group, Akita University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Akita Hip Research Group, Akita University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Akita Hip Research Group, Akita University Graduate School of Medicine kn-affil= en-keyword=hip fracture kn-keyword=hip fracture en-keyword=arthroplasty kn-keyword=arthroplasty en-keyword=bone cement kn-keyword=bone cement en-keyword=questionnaire kn-keyword=questionnaire END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=3 article-no= start-page=263 end-page=272 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Early Fluid Balance Is Associated with 90-Day Mortality in Patients Receiving Continuous Renal Replacement Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Continuous renal replacement therapy (CRRT) is widely used to control fluid balance, but the optimal fluid balance to improve the prognosis of patients remains debated. Appropriate fluid management may depend on hemodynamic status. We investigated the association between 90-day mortality and fluid balance/mean arterial pressure (MAP) in patients receiving CRRT. This single-center retrospective study was conducted between May 2018 and March 2021. Based on the cumulative fluid balance at 72 h after initiation of CRRT, the cases were divided into negative (< 0 mL) and positive (> 0 mL) fluid balance groups. Ninety-day mortality was higher in the positive fluid balance group (p=0.009). At 4 h before and after CRRT initiation, the mean MAP was lower in the positive fluid balance group (p<0.05). After multivariate cox adjustment, 72-h positive fluid balance was independently associated with 90-day mortality (p=0.004). In addition, the cumulative fluid balance was associated with 90-day mortality (p<0.05) in cases without shock, high APACHE II score, sepsis, dialysis dependence, or vasopressor use. A 72-h positive fluid balance was associated with 90-day mortality in patients receiving CRRT. en-copyright= kn-copyright= en-aut-name=GuoYusheng en-aut-sei=Guo en-aut-mei=Yusheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KosakaJunko en-aut-sei=Kosaka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=fluid management kn-keyword=fluid management en-keyword=continuous renal replacement therapy kn-keyword=continuous renal replacement therapy en-keyword=mortality kn-keyword=mortality en-keyword=mean arterial pressure kn-keyword=mean arterial pressure en-keyword=daily cumulative fluid balance kn-keyword=daily cumulative fluid balance END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=1 article-no= start-page=65 end-page=66 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ERRATA: FDM simulation of long-period ground motions around Oita Prefecture, Japan, using a land-ocean unified 3D structure model kn-title=訂正：地形を考慮した陸海統合3次元地震波速度構造モデルを用いた大分県周辺の長周期地震動シミュレーション en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OKUNAKATatsuya en-aut-sei=OKUNAKA en-aut-mei=Tatsuya kn-aut-name=奥仲達也 kn-aut-sei=奥仲 kn-aut-mei=達也 aut-affil-num=1 ORCID= en-aut-name=KOMATSUMasanao en-aut-sei=KOMATSU en-aut-mei=Masanao kn-aut-name=小松正直 kn-aut-sei=小松 kn-aut-mei=正直 aut-affil-num=2 ORCID= en-aut-name=TAKENAKAHiroshi en-aut-sei=TAKENAKA en-aut-mei=Hiroshi kn-aut-name=竹中博士 kn-aut-sei=竹中 kn-aut-mei=博士 aut-affil-num=3 ORCID= en-aut-name=YOSHIMIMasayuki en-aut-sei=YOSHIMI en-aut-mei=Masayuki kn-aut-name=吉見雅行 kn-aut-sei=吉見 kn-aut-mei=雅行 aut-affil-num=4 ORCID= en-aut-name=NAKAMURATakeshi en-aut-sei=NAKAMURA en-aut-mei=Takeshi kn-aut-name=中村武史 kn-aut-sei=中村 kn-aut-mei=武史 aut-affil-num=5 ORCID= en-aut-name=OKAMOTOTaro en-aut-sei=OKAMOTO en-aut-mei=Taro kn-aut-name=岡元太郎 kn-aut-sei=岡元 kn-aut-mei=太郎 aut-affil-num=6 ORCID= affil-num=1 en-affil=Formerly Department of Earth Sciences, Okayama University kn-affil=元・岡山大学理学部地球科学科 affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil=岡山大学大学院自然科学研究科 affil-num=3 en-affil=Department of Earth Sciences, Okayama University kn-affil=岡山大学学術研究院自然科学学域 affil-num=4 en-affil=Geological Survey of Japan, National Institute of Advanced Industrial Science and Technology kn-affil=国立研究開発法人産業技術総合研究所活断層・火山研究部門 affil-num=5 en-affil=Formerly Japan Agency for Marine-Earth Science and Technology kn-affil=元・国立研究開発法人海洋研究開発機構 affil-num=6 en-affil=Department of Earth and Planetary Sciences, School of Science, Tokyo Institute of Technology kn-affil=東京工業大学理学院地球惑星科学系 END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=1 article-no= start-page=49 end-page=63 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Onset time and location of the main rupture of the 2018 Hokkaido Eastern Iburi, Japan, earthquake kn-title=2018 年北海道胆振東部地震の初期の破壊過程 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The rupture process at the beginning stage of the 2018 Hokkaido Eastern Iburi, Japan, earthquake (MJ 6.7) is investigated by analyzing P-wave records from local strong-motion stations. The records show about 3 s of small amplitude arrival (so-called "initial rupture phase") followed by the onset of the main energy release ("main rupture phase"). In this paper we address the issue: where the seismic energy release corresponding to the main rupture phase started at the primary stage of the main rupture, by locating the main rupture onset position. For this aim we applied the 2D and the 3D search methods to estimate the relative location of the onset of the main rupture with respect to the hypocenter, and the time difference between them. The 2D method assumes a plausible initial fault plane and locates the main rupture onset position on the initial fault plane, while the 3D method does not require such assumed fault planes. In the 2D method we employed each of the nodal planes of the first-motion focal mechanism as the initial rupture plane. The 3D method was able to give a better solution than the 2D one. It suggests that the main rupture initiation point might not be on the same fault plane as the hypocenter is. The solution shows that the main rupture onset point is 5.8 km southward and 2.5 km upward from the hypocenter, with the rupture time of 3.3 s from the origin time. It is consistent with the previous studies on the relationship between the magnitude and the initial rupture duration. en-copyright= kn-copyright= en-aut-name=KOWARIHirofumi en-aut-sei=KOWARI en-aut-mei=Hirofumi kn-aut-name=小割啓史 kn-aut-sei=小割 kn-aut-mei=啓史 aut-affil-num=1 ORCID= en-aut-name=KOMATSUMasanao en-aut-sei=KOMATSU en-aut-mei=Masanao kn-aut-name=小松正直 kn-aut-sei=小松 kn-aut-mei=正直 aut-affil-num=2 ORCID= en-aut-name=TAKENAKAHiroshi en-aut-sei=TAKENAKA en-aut-mei=Hiroshi kn-aut-name=竹中博士 kn-aut-sei=竹中 kn-aut-mei=博士 aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Earth Sciences, Okayama University kn-affil=岡山大学大学院自然科学研究科 affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil=岡山大学大学院自然科学研究科 affil-num=3 en-affil=Department of Earth Sciences, Okayama University kn-affil=岡山大学学術研究院自然科学学域 en-keyword=2018 Hokkaido Eastern Iburi earthquake kn-keyword=2018 Hokkaido Eastern Iburi earthquake en-keyword=fault plane kn-keyword=fault plane en-keyword=initial rupture kn-keyword=initial rupture en-keyword=strong motion kn-keyword=strong motion END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230316 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dexmedetomidine improves acute lung injury by activating autophagy in a rat hemorrhagic shock and resuscitation model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dexmedetomidine (DEX) can reduce lung injury in a hemorrhagic shock (HS) resuscitation (HSR) model in rats by inhibiting inflammation. Here, we aimed to investigate if these effects of DEX are due to autophagy activation. Therefore, we established HSR rat models and divided them into four groups. HS was induced using a blood draw. The rats were then resuscitated by reinjecting the drawn blood and saline. The rats were sacrificed 24 h after resuscitation. Lung tissues were harvested for histopathological examination, determination of wet/dry lung weight ratio, and detection of the levels of autophagy-related marker proteins LC3, P62, Beclin-1, and the ATG12-ATG5 conjugate. The morphological findings of hematoxylin and eosin staining in lung tissues and the pulmonary wet/dry weight ratio showed that lung injury improved in HSR + DEX rats. However, chloroquine (CQ), an autophagy inhibitor, abolished this effect. Detecting the concentration of autophagy-related proteins showed that DEX administration increased LC3, ATG12-ATG5, and Beclin-1 expression and decreased P62 expression. The expression levels of these proteins were similar to those in the HSR group after CQ + DEX administration. In summary, DEX induced autophagic activation in an HSR model. These findings suggest that DEX administration partially ameliorates HSR-induced lung injury via autophagic activation. en-copyright= kn-copyright= en-aut-name=LuYifu en-aut-sei=Lu en-aut-mei=Yifu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimizuHiroko en-aut-sei=Shimizu en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraRyu en-aut-sei=Nakamura en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiYaqiang en-aut-sei=Li en-aut-mei=Yaqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoRisa en-aut-sei=Sakamoto en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriEmiko en-aut-sei=Omori en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiToru en-aut-sei=Takahashi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=8 en-affil=Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=4 article-no= start-page=2447 end-page=2457 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of perivascular fat attenuation on computed tomography and heart failure with preserved ejection fraction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims　Heart failure with a preserved ejection fraction (HFpEF) is associated with chronic inflammation. We aimed to investigate the association between pericoronary adipose tissue attenuation (PCATA) on coronary computed tomography angiography as a novel noninvasive marker of pericoronary inflammation and the presence of HFpEF.
Methods and results　This retrospective study included 607 outpatients (median age, 65 years; 50% male) who underwent both echocardiography and coronary computed tomography angiography. Patients with obstructive coronary artery disease were excluded from this study. PCATA was compared between patients with and without HFpEF, which was diagnosed according to the Heart Failure Association (HFA)-PEFF score. PCATA was assessed at the proximal 40-mm segments of all three major coronary arteries on coronary computed tomography angiography. Patients with HFpEF had higher PCATA in all coronary arteries compared to the control participants: left anterior descending artery (LAD), -65.2 +/- 6.9 Hounsfield units (HU) vs. -68.1 +/- 6.7 HU; left circumflex artery (LCX), -62.7 +/- 6.8 HU vs. -65.4 +/- 6.6 HU; and right coronary artery (RCA), -63.6 +/- 8.5 HU vs. -65.5 +/- 7.7 HU (P < 0.01). Multivariate logistic regression analysis, including conventional risk factors, revealed that PCATA per standard deviation in the LAD (odds ratio [OR], 1.449; 95% confidence interval [CI], 1.152-1.823), LCX (OR, 1.634; 95% CI, 1.283-2.081), and RCA (OR, 1.388; 95% CI, 1.107-1.740) were independently associated with HFpEF. The association between PCATA and HFpEF was mostly consistent across various patient clinical characteristics. The left ventricular mass and left atrial volume index showed a mild correlation with LAD-PCATA (rho = 0.13 [P rho = 0.24 [P < 0.01]) and LCX-PCATA (rho = 0.16 [P rho = 0.23 [P < 0.01]).
Conclusions　High PCATA score was significantly associated with the presence of HFpEF. Our results suggest that inflammation in the pericoronary artery adipose tissue is one of the underlying mechanisms of HFpEF. en-copyright= kn-copyright= en-aut-name=NishiharaTakahiro en-aut-sei=Nishihara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchikawaKeishi en-aut-sei=Ichikawa en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakayamaRie en-aut-sei=Nakayama en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Adipose tissue kn-keyword=Adipose tissue en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Coronary artery kn-keyword=Coronary artery en-keyword=Heart failure kn-keyword=Heart failure en-keyword=Inflammation kn-keyword=Inflammation END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=5 article-no= start-page=193 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230426 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diagnostic Performance of Cardiac Computed Tomography for Detecting Patent Foramen Ovale: Evaluation Using Transesophageal Echocardiography and Catheterization as Reference Standards en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Patent foramen ovale (PFO) is associated with various diseases such as cryptogenic stroke, migraine, and platypnea-orthodeoxia syndrome. This study aimed to evaluate the diagnostic performance of cardiac computed tomography (CT) for PFO detection. Materials and Methods: Consecutive patients diagnosed with atrial fibrillation and who underwent catheter ablation with pre-procedural cardiac CT and transesophageal echocardiography (TEE) were enrolled in this study. The presence of PFO was defined as (1) the confirmation of PFO using TEE and/or (2) the catheter crossing the interatrial septum (IAS) into the left atrium during ablation. CT findings indicative of PFO included (1) the presence of a channel-like appearance (CLA) on the IAS and (2) a CLA with a contrast jet flow from the left atrium to the right atrium. The diagnostic performance of both a CLA alone and a CLA with a jet flow was evaluated for PFO detection. Results: Altogether, 151 patients were analyzed in the study (mean age, 68 years; men, 62%). Twenty-nine patients (19%) had PFO confirmed by TEE and/or catheterization. The diagnostic performance of a CLA alone was as follows: sensitivity, 72.4%; specificity, 79.5%; positive predictive value (PPV), 45.7%; negative predictive value (NPV), 92.4%. The diagnostic performance of a CLA with a jet flow was as follows: sensitivity, 65.5%; specificity, 98.4%; PPV, 90.5%; NPV, 92.3%. The diagnostic performance of a CLA with a jet flow was statistically superior to that of a CLA alone (p = 0.045), and the C-statistics were 0.76 and 0.82, respectively. Conclusion: A CLA with a contrast jet flow in cardiac CT has a high PPV for PFO detection, and its diagnostic performance is superior to that of a CLA alone. en-copyright= kn-copyright= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IchikawaKeishi en-aut-sei=Ichikawa en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizunoTomofumi en-aut-sei=Mizuno en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakayamaRie en-aut-sei=Nakayama en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawadaSatoshi en-aut-sei=Kawada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AkagiTeiji en-aut-sei=Akagi en-aut-mei=Teiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil= Department of General Internal Medicine 3, Kawasaki Medical School kn-affil= en-keyword=patent foramen ovale kn-keyword=patent foramen ovale en-keyword=cardiac computed tomography kn-keyword=cardiac computed tomography en-keyword=transesophageal echocardiography kn-keyword=transesophageal echocardiography en-keyword=catheterization kn-keyword=catheterization en-keyword=channel-like appearance kn-keyword=channel-like appearance en-keyword=channel-like appearance with contrast jet flow kn-keyword=channel-like appearance with contrast jet flow END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=3 article-no= start-page=e0283426 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230329 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Consistently low levels of histidine-rich glycoprotein as a new prognostic biomarker for sepsis: A multicenter prospective observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Few sepsis biomarkers accurately predict severity and mortality. Previously, we had reported that first-day histidine-rich glycoprotein (HRG) levels were significantly lower in patients with sepsis and were associated with mortality. Since the time trends of HRG are unknown, this study focused on the time course of HRG in patients with sepsis and evaluated the differences between survivors and non-survivors.
Methods
A multicenter prospective observational study was conducted involving 200 patients with sepsis in 16 Japanese hospitals. Blood samples were collected on days 1, 3, 5, and 7, and 28-day mortality was used for survival analysis. Plasma HRG levels were determined using a modified quantitative sandwich enzyme-linked immunosorbent assay.
Results
First-day HRG levels in non-survivors were significantly lower than those in survivors (mean, 15.7 [95% confidence interval (CI), 13.4-18.1] vs 20.7 [19.5-21.9] mu g/mL; P = 0.006). Although there was no time x survivors/non-survivors interaction in the time courses of HRG (P = 0.34), the main effect of generalized linear mixed models was significant (P < 0.001). In a univariate Cox proportional hazards model with each variable as a time-dependent covariate, higher HRG levels were significantly associated with a lower risk of mortality (hazard ratio, 0.85 [95% CI, 0.78-0.92]; P < 0.001). Furthermore, presepsin levels (P = 0.02) and Sequential Organ Function Assessment scores (P < 0.001) were significantly associated with mortality. Harrell's C-index values for the 28-day mortality effect of HRG, presepsin, procalcitonin, and C-reactive protein were 0.72, 0.70, 0.63, and 0.59, respectively.
Conclusions
HRG levels in non-survivors were consistently lower than those in survivors during the first seven days of sepsis. Repeatedly measured HRG levels were significantly associated with mortality. Furthermore, the predictive power of HRG for mortality may be superior to that of other singular biomarkers, including presepsin, procalcitonin, and C-reactive protein. en-copyright= kn-copyright= en-aut-name=KawanoueNaoya en-aut-sei=Kawanoue en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaKosuke en-aut-sei=Kuroda en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasudaHiroko en-aut-sei=Yasuda en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OiwaMasahiko en-aut-sei=Oiwa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiSatoshi en-aut-sei=Suzuki en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HosoiHiroki en-aut-sei=Hosoi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Data Science Division, Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=西南日本中国地方の後期新生代火山岩のハフニウム・ホウ素・リチウム・マグネシウム同位体システマティクス：沈み込み帯で発生するスラブ由来の流体の特性と輸送メカニズムの解明 kn-title=Hf-B-Li-Mg isotope systematics of late Cenozoic volcanic rocks from the Chugoku district, Southwest Japan: Implications for the property and transport mechanism of slab-derived fluids in the subduction zone en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ZHANGWei en-aut-sei=ZHANG en-aut-mei=Wei kn-aut-name=张伟 kn-aut-sei=张 kn-aut-mei=伟 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama university kn-affil=岡山大学大学院自然科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=岡山での新型コロナウィルス流行時における自損行為による救急搬送－記述疫学研究 kn-title=Emergency Dispatches for Suicide Attempts During the COVID-19 Outbreak in Okayama, Japan: A Descriptive Epidemiological Study en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HABUHiroshi en-aut-sei=HABU en-aut-mei=Hiroshi kn-aut-name=土生裕 kn-aut-sei=土生 kn-aut-mei=裕 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=9 article-no= start-page=1319 end-page=1322 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fulminant Myocarditis for Non-small-cell Carcinoma of the Lung with Nivolumab and Ipilimumab Plus Chemotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 59-year-old man with a high level of antinuclear antibody received nivolumab and ipilimumab plus che-motherapy for lung cancer. Two weeks after the second course, he was admitted with a fever and severe fa-tigue. Laboratory studies showed elevated markers of myocardial damage, and a myocardial biopsy showed inflammatory cell infiltration, damaged myocardial fibers. Myocarditis was diagnosed as an immune-related adverse event (irAE), and high-dose corticosteroids were initiated. However, his cardiac function rapidly worsened, and he died on the fifth day after admission. There is no established treatment strategy for fulmi-nant myocarditis as an irAE, and the further exploration of viable treatment strategies is required. en-copyright= kn-copyright= en-aut-name=NishimuraTomoka en-aut-sei=Nishimura en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=myocarditis kn-keyword=myocarditis en-keyword=nivolumab plus ipilimumab kn-keyword=nivolumab plus ipilimumab en-keyword=irAE kn-keyword=irAE en-keyword=case report kn-keyword=case report END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=5 article-no= start-page=ytad214 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A successful bridge to recovery with Impella 5.0 and subsequent hybrid cardiac resynchronization therapy in systemic right ventricle failure: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background　Impella 5.0 is currently used as a temporary mechanical circulatory support device in cardiogenic shock (CS). However, Impella 5.0 implantation for the systemic right ventricle (sRV) has not been well documented.
Case summary　A 50-year-old man with atrial switch for dextro-transposition of the great arteries was transferred to our hospital for the treatment of embolic acute myocardial infarction of the left main trunk lesion with CS. To stabilize haemodynamics, we implanted Impella 5.0 via the left subclavian artery in the sRV. After optimal medical therapy initiation and gradual weaning of Impella 5.0, Impella 5.0 was successfully explanted. An electrocardiogram was obtained, which showed complete right branch block with a QRS duration of 172 ms. Acute invasive haemodynamic evaluation of cardiac resynchronization therapy (CRT) pacing showed that dP/dt increased from 497 to 605 mmHg/s (21.7% improvement), and hybrid cardiac resynchronization therapy defibrillator (CRTD) with a sRV epicardial lead was subsequently implanted. The patient was discharged without inotropic support.
Discussion　Coronary artery embolism is a rare but serious complication of dextro-transposition of the great arteries after atrial switch operations. Impella 5.0 implantation is a feasible bridge strategy for refractory CS due to sRV failure. Although CRT implantation in patients with sRV is controversial, an acute invasive haemodynamic evaluation can help assess its potential benefits. en-copyright= kn-copyright= en-aut-name=IwasakiKeiichiro en-aut-sei=Iwasaki en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Transposition of great arteries kn-keyword=Transposition of great arteries en-keyword=Impella kn-keyword=Impella en-keyword=Mechanical circulatory support kn-keyword=Mechanical circulatory support en-keyword=Cardiac resynchronization therapy kn-keyword=Cardiac resynchronization therapy en-keyword=Case report kn-keyword=Case report END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=6 article-no= start-page=e027046 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230321 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Heat Exposure Following the Rainy Season Is Associated With an Increased Risk of Cardiovascular Emergency Among the Elderly in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Despite the impact of heat exposure caused by global warming, few studies have investigated the hourly effects of heat exposure and the risk of cardiovascular disease (CVD) in the elderly. We examined the associations between short-term heat exposure and the risk of CVD in the elderly in Japan and evaluated possible effect-measure modifications by rainy seasons that occur in East Asia.
Methods and Results: We conducted a time-stratified case-crossover study. The study included 6527 residents in Okayama City, Japan, aged >= 65 years who were transported to emergency hospitals between 2012 and 2019 for the onset of CVD during and a few months after the rainy seasons. We examined the linear associations between temperature and CVD-related emergency calls for each year and for hourly preceding intervals before the emergency call during the most relevant months. Heat exposure during 1 month after the end of the rainy season was associated with CVD risk; the odds ratio (OR) for a 1 degrees C increase in temperature was 1.34 (95% CI, 1.29-1.40). When we further explored the nonlinear association by using the natural cubic spline model, we found a J-shaped relationship. Exposures 0 to 6 hours before the case event (preceding intervals 0-6 hours) were associated with CVD risk, particularly for the preceding interval 0 to 1 hour (OR, 1.33 [95% CI, 1.28-1.39]). For longer periods, the highest risk was at preceding intervals 0 to 23 hours (OR, 1.40 [95% CI, 1.34-1.46]).
Conclusions: Elderly individuals may be more susceptible to CVD after heat exposure during the month after the rainy season. As shown by finer temporal resolution analyses, short-term exposure to increasing temperature can trigger CVD onset. en-copyright= kn-copyright= en-aut-name=FujimotoRyohei en-aut-sei=Fujimoto en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KashimaSaori en-aut-sei=Kashima en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Environmental Health Sciences Laboratory, Graduate School of Advanced Science and Engineering, Hiroshima University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cardiovascular disease kn-keyword=cardiovascular disease en-keyword=climate change kn-keyword=climate change en-keyword=end of the rainy season kn-keyword=end of the rainy season en-keyword=heat exposure kn-keyword=heat exposure END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=22 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Delayed emergence from anesthesia caused by an intraoperative cerebral embolism of a malignant peripheral nerve sheath tumor in a neurofibromatosis type 1 patient: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background　Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas which commonly arise from neurofibromatosis type 1. Lung metastases of the tumors are well-known, but intraoperative cerebral tumor embolisms of MPNSTs have not been reported in literature.
Case presentation　A 52-year-old female patient with neurofibromatosis type 1 underwent a right lung partial resection for lung tumors. She was extubated after adequate recovery of spontaneous breathing; however, she could not respond to verbal commands. In the intensive care unit, her neurological examination revealed conjugate eye deviation, right hemiparalysis, and aphasia. Magnetic resonance imaging revealed acute cerebral ischemia, so she underwent an endovascular thrombectomy. The histopathological diagnosis of emboli was a MPNST, which was identical with that of the resected lung tumor.
Conclusion　We report the first case of delayed emergence caused by a cerebral tumor embolism of MPNST during partial lung resection. en-copyright= kn-copyright= en-aut-name=KawanoKeishi en-aut-sei=Kawano en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaniMakiko en-aut-sei=Tani en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Anesthesiology, Okayama City Hospital kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= en-keyword=Delayed emergence kn-keyword=Delayed emergence en-keyword=Cerebral tumor embolism kn-keyword=Cerebral tumor embolism en-keyword=Endovascular thrombectomy kn-keyword=Endovascular thrombectomy en-keyword=Neurofibromatosis type 1 kn-keyword=Neurofibromatosis type 1 en-keyword=Malignant peripheral nerve sheath tumor kn-keyword=Malignant peripheral nerve sheath tumor en-keyword=Lung surgery kn-keyword=Lung surgery END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=4 article-no= start-page=582 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230326 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Effect of Medical Cooperation in the CKD Patients: 10-Year Multicenter Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. Methods: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. Results: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 +/- 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). Conclusion: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD. en-copyright= kn-copyright= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaeshimaYohei en-aut-sei=Maeshima en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkuyamaYuka en-aut-sei=Okuyama en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtakaNozomu en-aut-sei=Otaka en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UjikeHaruyo en-aut-sei=Ujike en-aut-mei=Haruyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitagawaMasashi en-aut-sei=Kitagawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KinomuraMasaru en-aut-sei=Kinomura en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OtaKosuke en-aut-sei=Ota en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaruyamaKeisuke en-aut-sei=Maruyama en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HiramatsuMakoto en-aut-sei=Hiramatsu en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OshiroYoshiyuki en-aut-sei=Oshiro en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MoriokaShigeru en-aut-sei=Morioka en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TakiueKeiichi en-aut-sei=Takiue en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OmoriKazuyoshi en-aut-sei=Omori en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FukushimaMasaki en-aut-sei=Fukushima en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=GamouNaoyuki en-aut-sei=Gamou en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HirataHiroshi en-aut-sei=Hirata en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=5 en-affil=Kagawa Prefectural Central Hospital kn-affil= affil-num=6 en-affil=Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=National Hospital Organization Okayama Medical Center kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Okayama Saiseikai General Hospital kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=National Hospital Organization Okayama Medical Center kn-affil= affil-num=17 en-affil=Okayama Saiseikai General Hospital kn-affil= affil-num=18 en-affil=Okayama Saiseikai General Hospital, kn-affil= affil-num=19 en-affil=Kawasaki Medical School General Medical Center kn-affil= affil-num=20 en-affil=Okayama Central Hospital kn-affil= affil-num=21 en-affil=Okayama City Hospital kn-affil= affil-num=22 en-affil=Shigei Medical Research Hospital kn-affil= affil-num=23 en-affil=Shigei Medical Research Hospital kn-affil= affil-num=24 en-affil=Japanese Red Cross Okayama Hospital kn-affil= affil-num=25 en-affil=Akebono Clinic kn-affil= affil-num=26 en-affil=Sato Clinic kn-affil= affil-num=27 en-affil=Okayama University kn-affil= affil-num=28 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=chronic kidney disease (CKD) kn-keyword=chronic kidney disease (CKD) en-keyword=medical cooperation kn-keyword=medical cooperation en-keyword=patient care team kn-keyword=patient care team en-keyword=OCKD-NET kn-keyword=OCKD-NET END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=5 article-no= start-page=523 end-page=526 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Buruli ulcer caused by Mycobacterium ulcerans subsp. shinshuense: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Buruli ulcer is the third most common mycobacterial infection worldwide and is mainly diagnosed in tropical regions. Globally, this progressive disease is caused by Mycobacterium ulcerans; however, Mycobacterium ulcerans subsp. shinshuense, an Asian variant, has been exclusively identified in Japan. Because of insufficient clinical cases, the clinical features of M. ulcerans subsp. shinshuense–associated Buruli ulcer remain unclear. A 70-year-old Japanese woman presented with erythema on her left backhand. The skin lesion deteriorated without an apparent etiology of inflammation, and she was referred to our hospital 3 months after disease onset. A biopsy specimen was incubated in 2% Ogawa medium at 30 °C. After 66 days, we detected small yellow-pigmented colonies, suggesting scotochromogens. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI Biotyper; Bruker Daltonics, Billerica, MA, USA) indicated that the organism was Mycobacterium pseudoshottsii or Mycobacterium marinum. However, additional PCR testing for the insertion sequence 2404 (IS2404) was positive, suggesting that the pathogen was either M. ulcerans or M. ulcerans subsp. shinshuense. Further examination by 16S rRNA sequencing analysis, focusing on nucleotide positions 492, 1247, 1288, and 1449–1451, we finally identified the organism as M. ulcerans subsp. shinshuense. The patient was successfully treated with 12 weeks of clarithromycin and levofloxacin treatment. Mass spectrometry is the latest microbial diagnostic method; however, it cannot be used to identify M. ulcerans subsp. shinshuense. To accurately detect this enigmatic pathogen and uncover its epidemiology and clinical characteristics in Japan, more accumulation of clinical cases with accurate identification of the causative pathogen is essential. en-copyright= kn-copyright= en-aut-name=FujimoriTakumi en-aut-sei=Fujimori en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyamotoYuji en-aut-sei=Miyamoto en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoshinoYoshihiko en-aut-sei=Hoshino en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KakehiAyaka en-aut-sei=Kakehi en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkuraMami en-aut-sei=Okura en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MinabeHiroshi en-aut-sei=Minabe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YokoyamaYukika en-aut-sei=Yokoyama en-aut-mei=Yukika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HigashikageAkihito en-aut-sei=Higashikage en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Dermatology, Shimane University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases kn-affil= affil-num=6 en-affil=Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases kn-affil= affil-num=7 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=9 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=10 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= en-keyword=Buruli ulcer kn-keyword=Buruli ulcer en-keyword=Mycobacterium ulcerans kn-keyword=Mycobacterium ulcerans en-keyword=Mycobacterium ulcerans subsp kn-keyword=Mycobacterium ulcerans subsp en-keyword=shinshuense kn-keyword=shinshuense en-keyword=16S rRNA sequencing analysis kn-keyword=16S rRNA sequencing analysis END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=4 article-no= start-page=364 end-page=376 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between High Pericoronary Adipose Tissue Computed Tomography Attenuation and Impaired Flow-Mediated Dilation of the Brachial Artery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a noninvasive biomarker for pericoronary inflammation and is associated with cardiac mortality. We aimed to investigate the association between PCAT attenuation and endothelial dysfunction assessed using flow-mediated dilation (FMD).
Methods: A total of 119 outpatients who underwent both coronary CTA and FMD measurements were examined. PCAT attenuation values were assessed at the proximal 40-mm segments of all three major coronary arteries on coronary CTA. Endothelial function was assessed using FMD. Patients were then classified into two groups: those with endothelial dysfunction (FMD ＜4%, n=44) and those without endothelial dysfunction (FMD ≥ 4%, n=75).
Results: In all three coronary arteries, PCAT attenuation was significantly higher in patients with endothelial dysfunction than in those without endothelial dysfunction. Multivariate logistic regression analysis revealed that PCAT attenuation in the right coronary artery (odds ratio [OR]=1.543; 95% confidence interval [CI]=1.004–2.369, p=0.048) and left anterior descending artery (OR=1.525, 95% CI=1.004–2.369, p=0.049) was an independent predictor of endothelial dysfunction. Subgroup analysis of patients with adverse CTA findings (significant stenosis and/or high-risk plaque) and those with coronary artery calcium score ＞100 showed that high PCAT attenuation in all three coronary arteries was a significant predictor of endothelial dysfunction.
Conclusion: High PCAT attenuation was significantly associated with FMD-assessed endothelial dysfunction in patients with suspected coronary artery disease. Our results suggest that endothelial dysfunction is one of the pathophysiological mechanisms linking pericoronary inflammation to cardiac mortality. en-copyright= kn-copyright= en-aut-name=IchikawaKeishi en-aut-sei=Ichikawa en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhnoYuko en-aut-sei=Ohno en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiharaTakahiro en-aut-sei=Nishihara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TodaHironobu en-aut-sei=Toda en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshidaMasatoki en-aut-sei=Yoshida en-aut-mei=Masatoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medical technology, Kawasaki University of Medical Welfare kn-affil= affil-num=4 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Center kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Coronary computed tomography angiography kn-keyword=Coronary computed tomography angiography en-keyword=Perivascular coronary inflammation kn-keyword=Perivascular coronary inflammation en-keyword=Endothelial dysfunction kn-keyword=Endothelial dysfunction en-keyword=Flow-mediated dilation kn-keyword=Flow-mediated dilation END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue=5 article-no= start-page=e2022JB025670 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230425 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lithium Isotope Constraints on Slab and Mantle Contribution to Arc Magmas en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dehydration of subducting oceanic lithosphere (slab) induces Li-isotope fractionation between the fluid and the slab, suggested by the δ7Li variation (∼10‰) in exhumed subduction complexes. Given that arc magmas represent melt of the supraslab mantle, a large δ7Li variation is anticipated for arc volcanic rocks. However, the δ7Li values in these rocks are mostly homogeneous within the range of mid-ocean ridge basalts (+1.6 to +5.6‰). The lack of a subduction-related δ7Li signature has been explained by (1) homogenization by mixing of different magma sources, (2) loss of Li from the slab via dehydration, or (3) homogenization by diffusive exchange of slab-derived Li and the mantle. The Chugoku district in SW Japan is an ideal place to study the process responsible for Li-isotope variation in arc magmas, since the Chugoku volcanic rocks show large δ7Li variation (–1.9 to +7.4‰). High δ7Li values (+6.3 to +7.4‰) are found in some high-Sr andesites and dacites (adakites) whereas low δ7Li values (–1.0 to –0.1‰) are found in high-Mg andesites. The parental magmas of these rocks have been sourced from subducted oceanic crust and sediments, respectively, with various extents of the interaction with wedge mantle. The limited extents of Li isotope modification are indicated by the similarity of the δ7Li values of these rocks and their supposed sources. The models for a slab dehydration and a diffusive exchange between slab-derived melt and mantle demonstrate that the δ7Li signatures of the sources can be preserved in the adakites if they ascent rapidly in mantle. en-copyright= kn-copyright= en-aut-name=ZhangWei en-aut-sei=Zhang en-aut-mei=Wei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraEizo en-aut-sei=Nakamura en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= en-keyword=SW Japan kn-keyword=SW Japan en-keyword=slab kn-keyword=slab en-keyword=lithium isotope kn-keyword=lithium isotope en-keyword=arc magma kn-keyword=arc magma en-keyword=melt transport kn-keyword=melt transport END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230406 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanical stretching determines the orientation of osteoblast migration and cell division en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteoblasts alignment and migration are involved in the directional formation of bone matrix and bone remodeling. Many studies have demonstrated that mechanical stretching controls osteoblast morphology and alignment. However, little is known about its effects on osteoblast migration. Here, we investigated changes in the morphology and migration of preosteoblastic MC3T3-E1 cells after the removal of continuous or cyclic stretching. Actin staining and time-lapse recording were performed after stretching removal. The continuous and cyclic groups showed parallel and perpendicular alignment to the stretch direction, respectively. A more elongated cell morphology was observed in the cyclic group than in the continuous group. In both stretch groups, the cells migrated in a direction roughly consistent with the cell alignment. Compared to the other groups, the cells in the cyclic group showed an increased migration velocity and were almost divided in the same direction as the alignment. To summarize, our study showed that mechanical stretching changed cell alignment and morphology in osteoblasts, which affected the direction of migration and cell division, and velocity of migration. These results suggest that mechanical stimulation may modulate the direction of bone tissue formation by inducing the directional migration and cell division of osteoblasts. en-copyright= kn-copyright= en-aut-name=TakemotoFumiko en-aut-sei=Takemoto en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Uchida-FukuharaYoko en-aut-sei=Uchida-Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkamuraHirohiko en-aut-sei=Okamura en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkegameMika en-aut-sei=Ikegame en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, kn-affil= affil-num=4 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cell alignment kn-keyword=Cell alignment en-keyword=Cell division kn-keyword=Cell division en-keyword=Mechanical stress kn-keyword=Mechanical stress en-keyword=Migration kn-keyword=Migration en-keyword=Osteoblasts kn-keyword=Osteoblasts END start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue=2 article-no= start-page=79 end-page=85 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Multicenter clinical trials that take cardiovascular care one step further kn-title=循環器診療を一歩進める多施設共同臨床試験 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name=伊藤浩 kn-aut-sei=伊藤 kn-aut-mei=浩 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil=岡山大学学術研究院医歯薬学域　循環器内科学 en-keyword=多施設共同臨床試験 (multicentertrial) kn-keyword=多施設共同臨床試験 (multicentertrial) en-keyword=遠隔診療 (remote medicalcare) kn-keyword=遠隔診療 (remote medicalcare) en-keyword=動脈硬化性心血管疾患 (atherosclerotic cardiovascular disease) kn-keyword=動脈硬化性心血管疾患 (atherosclerotic cardiovascular disease) en-keyword=心不全 (heart failure) kn-keyword=心不全 (heart failure) en-keyword=糖尿病 (diabetes mellitus) kn-keyword=糖尿病 (diabetes mellitus) END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=2 article-no= start-page=161 end-page=167 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prolonged Double-Low Time and the Incidence of Postoperative Delirium in Surgical ICU Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=An intraoperative double-low condition is defined as concurrent low values for bispectral index (BIS) and mean arterial pressure (MAP), and may predict perioperative outcomes. We hypothesized that prolonged double-low times might be associated with an increased incidence of postoperative delirium. We conducted a single-center retrospective observational study on patients who had been admitted to our hospital’s intensive care unit (ICU) after surgery and whose BIS and MAP data had been recorded during general anesthesia. The primary outcome was the incidence of postoperative delirium. A double-low condition was defined as BIS < 45 and MAP <75 mmHg. The total double-low time was calculated in 1-min increments and used to divide the patients into quintiles. Multiple logistic regression analyses were conducted. Among the 334 patients included in the study, the incidence of postoperative delirium was 15.6% (n=52). Multiple logistic regression analysis revealed that a prolonged double-low time, defined as a total double-low time of > 42 min (i.e., third, fourth, and fifth quintiles), was significantly associated with an increased incidence of postoperative delirium (adjusted odds ratio: 2.61, 95% confidence interval: 1.27-5.37, p=0.009). Prolonged double-low time during general anesthesia was independently associated with an increased incidence of postoperative delirium in surgical ICU patients. en-copyright= kn-copyright= en-aut-name=YamanoiTomoko en-aut-sei=Yamanoi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiSatoshi en-aut-sei=Suzuki en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KakuRyuji en-aut-sei=Kaku en-aut-mei=Ryuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Intensive Care Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Anesthesiology, Mie University Hospital kn-affil= affil-num=4 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=postoperative delirium kn-keyword=postoperative delirium en-keyword=bispectral index kn-keyword=bispectral index en-keyword=hypotension kn-keyword=hypotension en-keyword=double-low condition kn-keyword=double-low condition en-keyword=general anesthesia kn-keyword=general anesthesia END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevalence of transthyretin amyloidosis among heart failure patients with preserved ejection fraction in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims Heart failure with preserved ejection fraction (HFpEF), which is caused by wide various conditions, has become a major public health problem. Transthyretin amyloid cardiomyopathy (ATTR-CM), which is thought to be an underdiagnosed disease, can cause HFpEF. Non-invasive diagnosis using 99mTechnetium (Tc)-pyrophosphate (PYP) scintigraphy enables accurate diagnosis of ATTR-CM. The aim of this study was to clarify the prevalence and characteristics of ATTR-CM among Japanese patients with HFpEF.
Methods and results This study was a multicentre, prospective, observational study conducted in Japan. We enrolled 373 patients with HFpEF [left ventricular (LV) ejection fraction ≥50%] aged ≥65 years who were admitted to the department of cardiology from September 2018 to January 2022. A 99mTc-PYP scintigraphy scan was performed during admission in all eligible patients. Cardiac 99mTc-PYP retention was graded according to a previously reported visual scale ranging from 0 to 3 points. The scan was considered positive when it revealed moderate-to-severe 99mTc-PYP uptake (Grade 2–3) in both ventricles. Patients were divided into ATTR-CM and non-ATTR-CM patients according to positive (Grade 2–3) or negative (Grade 0–1) 99mTc-PYP scintigraphy, respectively. Medical history, blood tests, electrocardiogram, echocardiography, and magnetic resonance imaging in the two groups of patients were compared. Among the 373 patients with HFpEF, 53 patients (14.2%; 95% confidence interval: 10.7–17.7) showed positive uptake on 99mTc-PYP scintigraphy. An endomyocardial biopsy was performed in 32 patients and confirmed amyloidosis in all cases. There were no significant differences between the two groups in age, severity of heart failure as assessed by the New York Heart Association (NYHA) functional classification, renal function values, left ventricular ejection fraction, and tricuspid regurgitant pressure gradient (ATTR-CM, n = 53 vs. non-ATTR-CM, n = 320). Patients in the ATTR-CM group had a higher N-terminal pro-brain natriuretic peptide level [2314 (1081–3398) vs. 900 (415–1828), P < 0.001], higher sensitive troponin T level (0.074 ± 0.049 vs. 0.035 ± 0.038, P < 0.001), and higher mean LV maximal wall thickness [12.5 (11–14) vs. 10.5 (9.5–11.5), P < 0.001].
Conclusions ATTR-CM is an underdiagnosed disease with a significant prevalence in Japanese patients with HFpEF. This study showed that results of examinations for ATTR-CM patients appear to be worse than those for non-ATTR-CM patients, but clinical severities of heart failure as assessed by the NYHA functional classification are similar in ATTR-CM and non-ATTR-CM patients, and the clinical overlap between ATTR-CM and non-ATTR-CM is high. en-copyright= kn-copyright= en-aut-name=NaitoTakanori en-aut-sei=Naito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AbeYukio en-aut-sei=Abe en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeHiroyuki en-aut-sei=Watanabe en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakuragiSatoru en-aut-sei=Sakuragi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaYusuke en-aut-sei=Katayama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KiharaHajime en-aut-sei=Kihara en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkizakiAtsutaka en-aut-sei=Okizaki en-aut-mei=Atsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawaiYusuke en-aut-sei=Kawai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshikawaMasaki en-aut-sei=Yoshikawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakaishiAtsushi en-aut-sei=Takaishi en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujioHideki en-aut-sei=Fujio en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtsukaHiroaki en-aut-sei=Otsuka en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OguraSoichiro en-aut-sei=Ogura en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ATTR HFpEF Registry Investigators en-aut-sei=ATTR HFpEF Registry Investigators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiology, Osaka City General Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Tokyo Bay Urayasu Ichikawa Medical Center kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Kihara Cardiovascular Clinic kn-affil= affil-num=8 en-affil=Department of Radiology, Asahikawa Medical University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama City Hospital kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=11 en-affil=Department of Cardiology, Mitoyo General Hospital kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil= kn-affil= en-keyword=Transthyretin amyloidosis kn-keyword=Transthyretin amyloidosis en-keyword=Heart failure kn-keyword=Heart failure en-keyword=Scintigraphy kn-keyword=Scintigraphy en-keyword=Left ventricular hypertrophy kn-keyword=Left ventricular hypertrophy END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=2183710 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electrochemical control of bone microstructure on electroactive surfaces for modulation of stem cells and bone tissue engineering en-subtitle= kn-subtitle= en-abstract= kn-abstract=Controlling stem cell behavior at the material interface is crucial for the development of novel technologies in stem cell biology and regenerative medicine. The composition and presentation of bio-factors on a surface strongly influence the activity of stem cells. Herein, we designed an electroactive surface that mimics the initial process of trabecular bone formation, by immobilizing chondrocyte-derived plasma membrane nanofragments (PMNFs) on its surface for rapid mineralization within 2 days. Moreover, the electroactive surface was based on the conducting polymer polypyrrole (PPy), which enabled dynamic control of the presentation of PMNFs on the surface via electrochemical redox switching, further resulting in the formation of bone minerals with different morphologies. Furthermore, bone minerals with contrasting surface morphologies had differential effects on the differentiation of human bone marrow-derived stem cells (hBMSCs) cultured on the surface. Together, this electroactive surface showed multifunctional characteristics, not only allowing dynamic control of PMNF presentation but also promoting the formation of bone minerals with different morphologies within 2 days. This electroactive substrate could be valuable for more precise control of stem cell growth and differentiation, and further development of more suitable microenvironments containing bone apatite for housing a bone marrow stem cell niche, such as biochips/bone-on-chips. en-copyright= kn-copyright= en-aut-name=CaoDanfeng en-aut-sei=Cao en-aut-mei=Danfeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MartinezJose G. en-aut-sei=Martinez en-aut-mei=Jose G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AnadaRisa en-aut-sei=Anada en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JagerEdwin W. H. en-aut-sei=Jager en-aut-mei=Edwin W. H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Sensor and Actuator Systems, Department of Physics, Chemistry and Biology (IFM), Linköping University kn-affil= affil-num=2 en-affil=Sensor and Actuator Systems, Department of Physics, Chemistry and Biology (IFM), Linköping University kn-affil= affil-num=3 en-affil=Advanced Research Center for Oral and Craniofacial Sciences Dental School, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Advanced Research Center for Oral and Craniofacial Sciences Dental School, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Sensor and Actuator Systems, Department of Physics, Chemistry and Biology (IFM), Linköping University kn-affil= en-keyword=Polypyrrole kn-keyword=Polypyrrole en-keyword=plasma membrane kn-keyword=plasma membrane en-keyword=redox switching kn-keyword=redox switching en-keyword=bone kn-keyword=bone en-keyword=chip kn-keyword=chip en-keyword=organ-on-chip kn-keyword=organ-on-chip END