start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e00463-25 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=Analysis of the drug target of the anti-tuberculosis compound OCT313: phosphotransacetylase is a potential drug target for anti-mycobacterial agents en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tuberculosis (TB) is one of the most common infectious diseases caused by bacteria worldwide. The increasing prevalence of multidrug-resistant TB (MDR-TB) and latent TB infection (LTBI) has intensified the global TB burden. Therefore, the development of new drugs for MDR-TB and LTBI is urgently required. We have reported that the derivative of dithiocarbamate sugar derivative, 2-acetamido-2-deoxy--D-glucopyranosyl N,N-dimethyldithiocarbamate (OCT313), exhibits anti-mycobacterial activity against MDR-MTB. Here, we identified the target of OCT313. In experimentally generated OCT313-resistant bacteria, adenine at position 1,092 in the metabolic enzyme phosphotransacetylase (PTA) gene was replaced with cytosine. This mutation is a nonsynonymous mutation that converts methionine to leucine at position 365 in the PTA protein. OCT313 inhibited the enzymatic activity of recombinant wild-type PTA, but not of the mutant PTA (M365L). PTA is an enzyme that produces acetyl-coenzyme A (acetyl-CoA) from acetyl phosphate and CoA and is involved in metabolic pathways; therefore, it was expected to also be active against dormant Mycobacterium tuberculosis bacilli. OCT313 exhibits antibacterial activity in the Wayne model of dormancy using Mycobacterium bovis BCG, and overexpression of PTA in OCT313-resistant bacilli restored sensitivity to OCT313. Collectively, the target of OCT313 is PTA, and OCT313 is a promising antimicrobial candidate for MDR-TB and LTBI. en-copyright= kn-copyright= en-aut-name=TakiiTakemasa en-aut-sei=Takii en-aut-mei=Takemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaTomohiro en-aut-sei=Hasegawa en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItohSaotomo en-aut-sei=Itoh en-aut-mei=Saotomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaedaShinji en-aut-sei=Maeda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WadaTakayuki en-aut-sei=Wada en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoritaYasuhiro en-aut-sei=Horita en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiyamaAkihito en-aut-sei=Nishiyama en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoSohkichi en-aut-sei=Matsumoto en-aut-mei=Sohkichi 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= en-aut-name=KimishimaAoi en-aut-sei=Kimishima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsamiYukihiro en-aut-sei=Asami en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HidaShigeaki en-aut-sei=Hida en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OnozakiKikuo en-aut-sei=Onozaki en-aut-mei=Kikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=2 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=3 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=4 en-affil=Graduate School of Pharmaceutical Sciences, Hokkaido University of Sciences kn-affil= affil-num=5 en-affil=Department of Microbiology, Graduate School of Human Life and Ecology, Osaka Metropolitan University kn-affil= affil-num=6 en-affil=Department of Clinical Pharmaceutics, Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=7 en-affil=Department of Bacteriology, Niigata University School of Medicine kn-affil= affil-num=8 en-affil=Department of Bacteriology, Niigata University School of Medicine kn-affil= affil-num=9 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=11 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=12 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=13 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= en-keyword=phosphotransacetylase kn-keyword=phosphotransacetylase en-keyword=acetyl coenzyme A kn-keyword=acetyl coenzyme A en-keyword=dithiocarbamate kn-keyword=dithiocarbamate en-keyword=N-acetyl glucosamine kn-keyword=N-acetyl glucosamine en-keyword=anti-mycobacterial agents kn-keyword=anti-mycobacterial agents en-keyword=latent tuberculosis infection kn-keyword=latent tuberculosis infection END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=40522 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long intervals between repetitive concussions reduce risk of cognitive impairment and limit microglial activation, astrogliosis, and tauopathy in adolescent rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although previous studies have demonstrated the effects of concussions do not accumulate as the time interval between injuries increases, little is known about the relationship between this interval and the effects of repetitive concussions. The objective of this study is to explore the relationship between the time interval and changes in behavior and histology following repetitive concussions. Male adolescent rats received concussions by weight drop and were randomly assigned to one of five experimental groups, receiving concussions three times either daily, every other day, once per week, once every 2 weeks, or receiving sham procedures. Only rats that received daily concussions exhibited cognitive impairment, while the other groups did not. No groups showed motor or anxiety-like impairments. Histological analysis revealed accumulation of microglia, as well as astrogliosis, in the prefrontal cortex, corpus callosum, dentate gyrus, and cornu Ammonis 1 region of the hippocampus in rats subjected to daily concussions. Accumulation of phosphorylated tau was also observed in the prefrontal cortex and cornu Ammonis 1. Longer intervals between concussions may reduce the risk of cognitive impairment and limit microglial activation, astrogliosis, and phosphorylated tau accumulation. These findings may help guide decisions on the appropriate timing for return to play in humans. en-copyright= kn-copyright= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinKyohei en-aut-sei=Kin en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaseTakayuki en-aut-sei=Nagase en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiTatsuya en-aut-sei=Sasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugaharaChiaki en-aut-sei=Sugahara en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaiKoji en-aut-sei=Kawai en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanimotoShun en-aut-sei=Tanimoto en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyakeHayato en-aut-sei=Miyake en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaijoTomoya en-aut-sei=Saijo en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital 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, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Yasuhara Clinic kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= en-keyword=Concussion kn-keyword=Concussion en-keyword=Return to play kn-keyword=Return to play en-keyword=Sports-related head injury kn-keyword=Sports-related head injury en-keyword=Microglia kn-keyword=Microglia en-keyword=Astrocyte kn-keyword=Astrocyte en-keyword=Tauopathy kn-keyword=Tauopathy END 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=27 cd-vols= no-issue=1 article-no= start-page=219 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Does perioperative discontinuation of anti-rheumatic drugs increase postoperative complications in orthopedic surgery for rheumatoid arthritis? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective This study aimed to investigate whether discontinuation of biological or targeted synthetic antirheumatic disease-modifying drugs (bDMARDs or tsDMARDs) influences the incidence of postoperative complications in patients with rheumatoid arthritis (RA) undergoing orthopedic surgery.
Methods A retrospective multicenter cohort study including patients receiving bDMARDs or tsDMARDs who underwent orthopedic surgery was conducted. Data collected encompassed the duration of drug discontinuation and postoperative adverse events, such as delayed wound healing, surgical site infection (SSI), disease flare-ups, and mortality. The association between drug discontinuation and these outcomes was analyzed. Multivariate analyses were conducted to identify potential risk factors for these events.
Results A total of 2,060 cases were initially enrolled. After applying inclusion and exclusion criteria, data from 1,953 patients were analyzed. No significant differences were observed between the groups regarding delayed wound healing, SSI, or mortality. However, the incidence of disease flare-ups was substantially higher in the drug discontinuation group and in the interleukin (IL)-6 inhibitor group. Multivariate analysis identified that tumor necrosis factor and IL-6 inhibitor use was associated with a higher risk of delayed wound healing relative to T-cell function modifiers.
Conclusion In orthopedic surgery for patients with RA, maintaining the standard or the half of administration interval of bDMARD appears safe in the preoperative period. However, the drug discontinuation may increase the risk of postoperative flare-ups, particularly with IL-6 inhibitors. In addition, T-cell function modifiers may be associated with a lower risk of delayed wound healing, suggesting their safety profile in this context. en-copyright= kn-copyright= en-aut-name=ItoHiromu en-aut-sei=Ito en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaHajime en-aut-sei=Ishikawa en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiShigeyoshi en-aut-sei=Tsuji en-aut-mei=Shigeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MochizukiTakeshi en-aut-sei=Mochizuki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EbinaKosuke en-aut-sei=Ebina en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=MatsumotoTakumi en-aut-sei=Matsumoto en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KubotaAyako en-aut-sei=Kubota en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakajimaArata en-aut-sei=Nakajima en-aut-mei=Arata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KanekoAtsushi en-aut-sei=Kaneko en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsushitaIsao en-aut-sei=Matsushita en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HaraRyota en-aut-sei=Hara en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakurabaKoji en-aut-sei=Sakuraba en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=AkasakiYukio en-aut-sei=Akasaki en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsubaraTsukasa en-aut-sei=Matsubara en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MochidaYuichi en-aut-sei=Mochida en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KanbeKatsuaki en-aut-sei=Kanbe en-aut-mei=Katsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NakagawaNatsuko en-aut-sei=Nakagawa en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MurataKoichi en-aut-sei=Murata en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MomoharaShigeki en-aut-sei=Momohara en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Kurashiki Central Hospital kn-affil= affil-num=2 en-affil=Department of Rheumatology, Niigata Rheumatic Center kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Osaka Minami Medical Center kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, International University of Health and Welfare kn-affil= affil-num=5 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Kamagaya General Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Osaka University Faculty of Medicine Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Nagoya University Hospital kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, University of Tokyo kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Toho University Omori Medical Center kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery and Rehabilitation, Toho University Sakura Medical Center kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Nagoya Medical Center kn-affil= affil-num=13 en-affil=Department of Rehabilitation Medicine, Kanazawa Medical University kn-affil= affil-num=14 en-affil=The Center for Rheumatic Diseases, Nara Medical University kn-affil= affil-num=15 en-affil=Department of Orthopaedic Surgery, Kyushu Medical Center kn-affil= affil-num=16 en-affil=Department of Orthopaedic Surgery, Kyushu University kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Matsubara Mayflower Hospital kn-affil= affil-num=18 en-affil=Department of Orthopaedic Surgery, Yokohama City University Medical Center kn-affil= affil-num=19 en-affil=Department of Orthopaedic Surgery, Nippori Orthopaedics and Rheumatic Clinic kn-affil= affil-num=20 en-affil=Department of Orthopaedic Surgery, Kakogawa Medical Center kn-affil= affil-num=21 en-affil=Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Endowed Course for Advanced Therapy for Musculoskeletal Disorders, Keio University School of Medicine kn-affil= en-keyword=Rheumatoid arthritis kn-keyword=Rheumatoid arthritis en-keyword=Orthopaedic surgery kn-keyword=Orthopaedic surgery en-keyword=DMARD kn-keyword=DMARD en-keyword=Perioperative complications kn-keyword=Perioperative complications 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-1-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-1-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/g 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=1873 cd-vols= no-issue=2 article-no= start-page=120091 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=SPRED2 controls the severity of cisplatin-induced acute kidney injury by inhibiting ERK activation and TNF production in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cisplatin is an effective chemotherapeutic agent used to treat solid tumors, but its clinical use is limited by acute kidney injury (AKI), in which ERK signaling plays a crucial role. Here, we investigated whether Sprouty-related EVH1 domain-containing protein 2 (SPRED2), an endogenous inhibitor of the Ras/Raf/ERK pathway, protects against cisplatin-induced AKI. Spred2?/? mice showed more severe renal injury and stronger ERK activation than wild-type (WT) mice, whereas pretreatment with the MEK inhibitor U0126 markedly attenuated the injury. In HK-2 cells (proximal tubular cells), SPRED2 knockdown enhanced cisplatin-induced apoptosis and caspase-3 activation, accompanied by decreased Bcl-2 expression. Spred2?/? kidneys displayed increased macrophage infiltration and elevated Tnf, Il1b, and Ccl2 expression. Neutralization of TNF with anti-TNF antibody ameliorated renal injury and reduced the levels of Il1b and Ccl2 mRNA in Spred2?/? mice. In vitro, TNF slightly decreased the viability of control and SPRED2 knockdown HK-2 cells without cisplatin treatment, but the decreased viability was augmented in SPRED2 knockdown cells by cisplatin. Immunohistochemistry revealed that macrophages were the predominant TNF-positive cell population. Bone marrow?derived macrophages from Spred2?/? mice produced higher levels of TNF in response to cisplatin compared with control cells, and this increase was markedly suppressed by U0126.
These findings indicate that endogenous SPRED2 protects kidneys from cisplatin-induced AKI by limiting ERK activation, tubular apoptosis, and TNF-mediated inflammation. en-copyright= kn-copyright= en-aut-name=YangXu en-aut-sei=Yang en-aut-mei=Xu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HeJiali en-aut-sei=He en-aut-mei=Jiali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=KunkelSteven L. en-aut-sei=Kunkel en-aut-mei=Steven L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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 Pathology, University of Michigan Medical School kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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= en-keyword=Cisplatin kn-keyword=Cisplatin en-keyword=ERK kn-keyword=ERK en-keyword=Macrophage kn-keyword=Macrophage en-keyword=SPRED2 kn-keyword=SPRED2 en-keyword=TNF kn-keyword=TNF END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=12 article-no= start-page=1455 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of ROS and NO in Plant Responses to Individual and Combined Salt Stress and Waterlogging en-subtitle= kn-subtitle= en-abstract= kn-abstract=During the climate change era, plants are increasingly exposed to multiple environmental challenges occurring simultaneously or sequentially. Among these, salt stress and waterlogging are two major factors that severely constrain crop productivity worldwide and often occur together. To survive under such conditions, plants have evolved sophisticated systems to scavenge harmful levels of reactive oxygen species (ROS). Despite their cytotoxic potential, ROS also act as key signaling molecules that interact with nitric oxide (NO), Ca2+, protein kinases, ion homeostasis pathways, and plant hormones. These signaling and acclimatory mechanisms are closely associated with the functions of energy-regulating organelles?chloroplasts and mitochondria?which are major sources of ROS under both individual and combined stresses. While many of these responses are shared between salt stress, waterlogging and their combination, it is likely that specific signaling mechanisms are uniquely activated when both stresses occur together?mechanisms that cannot be inferred from responses to each stress alone. Such specificity may depend on precise coordination among organelle-derived signals and the tight regulation of their cross-communication. Within this network, ROS and NO likely serve as central hubs, fine-tuning the integration of multiple signaling pathways that enable plants to adapt to complex and fluctuating stress environments. en-copyright= kn-copyright= en-aut-name=AneeTaufika Islam en-aut-sei=Anee en-aut-mei=Taufika Islam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SewelamNasser A. en-aut-sei=Sewelam en-aut-mei=Nasser A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BautistaNonnatus S. en-aut-sei=Bautista en-aut-mei=Nonnatus S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirayamaTakashi en-aut-sei=Hirayama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University kn-affil= affil-num=2 en-affil=Botany Department, Faculty of Science, Tanta University kn-affil= affil-num=3 en-affil=Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Ba?os kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University kn-affil= en-keyword=chloroplasts kn-keyword=chloroplasts en-keyword=mitochondria kn-keyword=mitochondria en-keyword=nitric oxide (NO) kn-keyword=nitric oxide (NO) en-keyword=reactive oxygen species (ROS) kn-keyword=reactive oxygen species (ROS) en-keyword=salt stress kn-keyword=salt stress en-keyword=stress combination waterlogging kn-keyword=stress combination waterlogging 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=20251127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Avoiding splenectomy in splenic sclerosing angiomatoid nodular transformation through endoscopic ultrasound-guided tissue acquisition: a 36-month follow-up case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 48-mm splenic mass was incidentally discovered in a 78-year-old man upon computed tomography. Follow-up imaging at 12 months revealed enlargement to 60 mm, prompting endoscopic ultrasound-guided tissue acquisition with a 22-gauge needle. Histopathological analysis confirmed that it was a sclerosing angiomatoid nodular transformation. The patient was asymptomatic and had no hematologic abnormalities; therefore, splenectomy was not performed. After biopsy, the lesion regressed from 60 mm to 46 mm, possibly owing to hematoma formation or vascular disruption, and remained stable during 36 months of follow-up. Although splenectomy has been performed in most reported cases of sclerosing angiomatoid nodular transformation because of diagnostic uncertainty, a few recent reports have demonstrated that sclerosing angiomatoid nodular transformation can be diagnosed by endoscopic ultrasound-guided tissue acquisition, thereby avoiding splenectomy. This case highlights the diagnostic utility of endoscopic ultrasound-guided tissue acquisition and supports spleen-preserving management for biopsy-proven sclerosing angiomatoid nodular transformation. en-copyright= kn-copyright= en-aut-name=OkuyamaTakaki en-aut-sei=Okuyama en-aut-mei=Takaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MorimotoKosaku en-aut-sei=Morimoto en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KimuraShogo en-aut-sei=Kimura en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyakeTakayoshi en-aut-sei=Miyake en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatomiTakuya en-aut-sei=Satomi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeiKensuke en-aut-sei=Takei en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InoueShogo en-aut-sei=Inoue en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakenakaRyuta en-aut-sei=Takenaka en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=5 en-affil=Department of Pathology, Tsuyama Chuo Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=8 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=9 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= en-keyword=Sclerosing angiomatoid nodular transformation kn-keyword=Sclerosing angiomatoid nodular transformation en-keyword=Spleen kn-keyword=Spleen en-keyword=Endoscopic ultrasound-guided tissue acquisition kn-keyword=Endoscopic ultrasound-guided tissue acquisition en-keyword=Conservative management kn-keyword=Conservative management en-keyword=Biopsy kn-keyword=Biopsy 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=20251123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A rare case of supratentorial ependymosarcoma harboring ZFTA::RELA fusion en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ependymosarcoma is an exceedingly rare variant of ependymoma characterized by a mixture of ependymomatous and sarcomatous components. We report a case of supratentorial ependymosarcoma harboring a ZFTA::RELA fusion in a 10-year-old girl. Histologically, the tumor comprised an ependymomatous component resembling clear cell ependymoma and a sarcomatous component. ZFTA::RELA fusion was confirmed in both components. Genome-wide methylation profiling classified both components as supratentorial ependymoma, ZFTA fusion?positive by the German Cancer Research Center (DKFZ) CNS tumor classifier v12b8. However, their copy number alteration profiles were distinct. The ependymomatous component exhibited a gain of chromosome 1q and a loss of chromosomes 1p, 9, and 19q, while the sarcomatous component showed a loss of chromosome 14. These findings suggest that both components may have differentiated from a common precursor despite their distinct morphologies. The patient underwent gross total resection followed by adjuvant chemoradiotherapy and remains recurrence-free eight years post-treatment. Further investigation of additional cases is warranted to better understand the pathogenesis of this rare tumor. en-copyright= kn-copyright= en-aut-name=MatsumotoYuji en-aut-sei=Matsumoto en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SurugaYasuki en-aut-sei=Suruga en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatomiKaishi en-aut-sei=Satomi en-aut-mei=Kaishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueYohei en-aut-sei=Inoue en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HattoriYasuhiko en-aut-sei=Hattori en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KurozumiKazuhiko en-aut-sei=Kurozumi en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NobusawaSumihito en-aut-sei=Nobusawa en-aut-mei=Sumihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiratoJunko en-aut-sei=Hirato en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IchimuraKoichi en-aut-sei=Ichimura en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IchikawaTomotsugu en-aut-sei=Ichikawa en-aut-mei=Tomotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Pathology, Faculty of Medicine, Kyorin University kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Neurosurgery, Hamamatsu University Hospital kn-affil= affil-num=8 en-affil=Department of Human Pathology, Gunma University School of Medicine kn-affil= affil-num=9 en-affil=Department of Pathology, Public Tomioka General Hospital kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Pathology, Faculty of Medicine, Kyorin University kn-affil= affil-num=14 en-affil=Department of Neurosurgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Ependymoma kn-keyword=Ependymoma en-keyword=Ependymosarcoma kn-keyword=Ependymosarcoma en-keyword=ZFTA kn-keyword=ZFTA en-keyword=RELA kn-keyword=RELA en-keyword=Methylation profiling kn-keyword=Methylation profiling END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=6 article-no= start-page=104265 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel leukocytapheresis method using highly concentrated sodium citrate solution for the manufacturing of tisagenlecleucel en-subtitle= kn-subtitle= en-abstract= kn-abstract=For the manufacturing of tisagenlecleucel (tisa-cel) requires the non-mobilized mononuclear cell collection (MNC). CD3+ cell collection is performed using the same protocol as autologous peripheral blood stem cell harvest (auto-PBSCH), but this procedure necessitates the same target CD3+ cell yields regardless of age or body weight, which may take several days especially in pediatric and small female patients with low white blood cell counts. We previously demonstrated a novel method using highly concentration sodium citrate (HSC), which reduced the need for an anticoagulant (AC) solution and shortened the procedure time in auto-PBSCH. This novel method was expected to offer advantages for smaller patients, prompting us to investigate its application in leukocytapheresis for the manufacturing of tisa-cel. We retrospectively analyzed consecutive leukocytapheresis data obtained using Spectra Optia continuous MNC mode between November 2022 and June 2024 at our institution (n?=?9). In six of nine patients, pre-leukocytapheresis CD3+ cell counts were less than 500 /L, but all could obtain the target CD3+ cell yields in one day upon processing blood volume adjustment. When we compared patients who had received CD3+ cell collection using normal-concentration sodium citrate (NSC) as our previously reported using propensity score-matched pair analysis, the total AC solution volume was significantly lower (1168 vs. 316?mL, p? Study Design and Methods: We retrospectively analyzed consecutive auto-PBSCH data obtained using the Spectra Optia continuous mononuclear cell collection mode between May 2017 and May 2025 at our institution.
Results: Leukocytapheresis was performed using NSC in 36 patients and HSC in 22. In the HSC group, patients tended to be younger, had significantly lower body weight, and had significantly fewer hematopoietic tumors as primary diseases compared to the NSC group. After propensity score-matched cohort adjusted for patient background, the total amount of AC solution was significantly lower (694 [range, 77?1648] vs. 298?mL [range, 64?797], p?=?.02), and procedure time was significantly shorter (224 [range, 117?395] vs. 181?min [range, 103?309], p?=?.048) in the HSC group. Furthermore, the loss rates of magnesium and potassium were lower in the HSC group.
Conclusion: This novel leukocytapheresis method demonstrated the efficacy and safety in auto-PBSCH, while minimizing the patient burden. en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkeuchiKazuhiro en-aut-sei=Ikeuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimonoJoji en-aut-sei=Shimono en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=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=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=acid citrate dextrose solution A kn-keyword=acid citrate dextrose solution A en-keyword=anticoagulant kn-keyword=anticoagulant en-keyword=autologous kn-keyword=autologous en-keyword=highly concentrated sodium citrate kn-keyword=highly concentrated sodium citrate en-keyword=peripheral blood stem cell kn-keyword=peripheral blood stem cell END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e95808 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=Risk Stratification for the Prediction of Skeletal-Related Events in Patients With Bone Metastases From Non-small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Skeletal-related events (SREs) frequently occur in patients with bone metastases from non-small cell lung cancer (NSCLC). This study aimed to identify risk factors for SREs in patients with NSCLC. Based on these factors, we also aimed to stratify patients into subgroups to facilitate the assessment of SRE risk. This retrospective analysis used medical records of 139 patients with NSCLC bone metastases who received treatment at our institution between 2011 and 2014. The incidence of SREs was assessed, and SRE-free survival was analyzed using the Kaplan-Meier method. Clinical information collected at registration was assessed to identify factors associated with the onset of SREs within six months. Univariate analysis was performed using Fisherfs exact test, and multivariate analysis was performed using Cox regression. Of the 139 patients, 36 (26%) developed SREs after registration. The SRE-free survival rates were 80% and 64% at 6 and 12 months, respectively. The univariate and multivariate analyses revealed that the absence of epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangement (hazard ratio (HR): 4.51, 95% confidence interval (CI): 1.32-15.7, p = 0.017) and a lactate dehydrogenase (LDH) level ?400 U/L (HR: 8.08, 95% CI: 1.78-36.6, p = 0.0067) were risk factors for SRE presentation within six months. Patients were classified into the following three subgroups: with EGFR mutation or ALK rearrangement and LDH level <400 U/L; without EGFR mutation or ALK rearrangement and LDH level <400 U/L; with/without EGFR mutation or ALK rearrangement and LDH level ?400 U/L. The corresponding six-month SRE-free survival rates were 92%, 69%, and 34%, respectively, showing significant differences (p < 0.001). Close monitoring is recommended for patients with LDH levels ?400 U/L in daily clinical practice, particularly with the help of the proficiency of orthopedic and radiological experts, to prevent complications such as pathological fractures and paraplegia. en-copyright= kn-copyright= en-aut-name=SakamotoYoshihiro en-aut-sei=Sakamoto en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaMasanori en-aut-sei=Hamada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatayamaYoshimi en-aut-sei=Katayama en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiharaShinsuke en-aut-sei=Sugihara en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anaplastic lymphoma kinase kn-keyword=anaplastic lymphoma kinase en-keyword=bone metastases kn-keyword=bone metastases en-keyword=epidermal growth factor receptor-tyrosine kinase kn-keyword=epidermal growth factor receptor-tyrosine kinase en-keyword=lactate dehydrogenase kn-keyword=lactate dehydrogenase en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=skeletal related events kn-keyword=skeletal related events END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3 article-no= start-page=e80656 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250316 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Charcot Spine Arthropathy at the Lumbosacral Level in a Patient With Ankylosis of the Spine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Charcot spinal arthropathy, a rare refractory progressive disease, is characterized by symptoms such as pain, deformity, and neurological impairment, which can significantly reduce functional ability, quality of life, and life expectancy. We report a case of Charcot spine at the L5/S1 level with long segment ankylosis to the L5 vertebra. We first performed thorough debridement via a posterior approach. We used antibiotic-containing cement as a spacer to fill the dead space, facilitating the second surgery approach. In the second surgery, transdiscal screws, which have a low profile and strong force, were used as anchors, and bulk bone harvested from both iliac bones was grafted to the intervertebral space. The lumbosacral alignment was kyphotic, and the patient could sit and move independently. Disimpaction was impossible, and a stoma had to be created. en-copyright= kn-copyright= en-aut-name=OdaYoshiaki en-aut-sei=Oda en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TetsunagaTomoko en-aut-sei=Tetsunaga en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinoharaKensuke en-aut-sei=Shinohara en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Musculoskeletal Traumatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=ankylosing spine kn-keyword=ankylosing spine en-keyword=charcot spine kn-keyword=charcot spine en-keyword=charcot spine arthropathy kn-keyword=charcot spine arthropathy en-keyword=lumbosacral segment kn-keyword=lumbosacral segment en-keyword=paraplegia kn-keyword=paraplegia en-keyword=transdiscal screw kn-keyword=transdiscal screw 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=CEJ‰^𐧌䂷VCkiYi̍EӍזECa2+`lCNGC2̋@\ kn-title=Functional characterization of a guard cell Ca2+ channel 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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=XɂĎᇊ֘AۉזẺe󂯂DIL-8ĎᇑiIȂ͂炫s kn-title=Cancer?associated fibroblasts promote pro?tumor functions of neutrophils in pancreatic cancer via IL?8: potential suppression by pirfenidon en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YAGITomohiko en-aut-sei=YAGI en-aut-mei=Tomohiko kn-aut-name=ؒF kn-aut-sei= kn-aut-mei=F aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w 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=ADAR1̎ᇊ֘A}Nt@[W͉wÖ@UĂAÕWIƂȂ”\ 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= en-copyright= kn-copyright= en-aut-name=OTSUKI (UMEDA)Hibiki en-aut-sei=OTSUKI (UMEDA) en-aut-mei=Hibiki kn-aut-name=΁i~cj kn-aut-sei=΁i~cj 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=Rww@㎕w 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=EGFRMETWIƂdِR̂łA~o^}uALKZ`qz񏬍זExזEɑ΂L kn-title=Efficacy of amivantamab, a bi-specific antibody targeting EGFR and MET, in ALK-rearranged non-small-cell lung cancer cell lines en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NISHITatsuya en-aut-sei=NISHI en-aut-mei=Tatsuya kn-aut-name=B kn-aut-sei= kn-aut-mei=B aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w 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=HIF-PHjQ܂TזEɋ[_fԂUARᇖƉu𑝋邱ƂŃ}CNTeCg^咰̑B} 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= en-copyright= kn-copyright= en-aut-name=CHENYUEHUA en-aut-sei=CHEN en-aut-mei=YUEHUA kn-aut-name=?x? kn-aut-sei=? kn-aut-mei=x? aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w 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=֘AۉזEUC^[CL6WIƂ݊]ڂɑ΂VKÐ헪 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= en-copyright= kn-copyright= en-aut-name=MITSUIEma en-aut-sei=MITSUI en-aut-mei=Ema kn-aut-name=b kn-aut-sei= kn-aut-mei=b aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w 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=_opɂ`זElpזẼVOZтɋԉ kn-title=Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KOBAYASHIHiroki en-aut-sei=KOBAYASHI en-aut-mei=Hiroki kn-aut-name=эGI kn-aut-sei= kn-aut-mei=GI aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w 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=EGFR`qψٗzxɂRj[hq-1ȇjQ܂ɂ}Nt@[W}IV`juURᇖƉȗ kn-title=Colony-stimulating factor-1 receptor inhibitor augments osimertinib-induced anti-tumor immunity via suppression of macrophages in lung cancer harboring EGFR mutation en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OKAWASachi en-aut-sei=OKAWA en-aut-mei=Sachi 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=Rww@㎕w 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=2^Aa҂ɂH㒆bl̕ϓƐt@\QAʃAu~AƂ̊֘Aɂ‚:ώ@ kn-title=The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UCHIYAMANatsumi en-aut-sei=UCHIYAMA en-aut-mei=Natsumi kn-aut-name=RޒÎ kn-aut-sei=R kn-aut-mei=ޒÎ aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w 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`-X̔DPAaɂ kn-title=Role of galectin-9 in the development of gestational diabetes mellitus en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ALBUAYJAN HAYA HAMED H en-aut-sei=ALBUAYJAN HAYA HAMED H en-aut-mei= 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=Rww@㎕w 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=o^NXɂ铱Ö@́AAu~lႢɂ炸A`Iv^̓ᇐ咰҂ɒIȗv炷 kn-title=Induction Therapy With Oral Tacrolimus Provides Long-Term Benefit in Thiopurine-Na?ve Refractory Ulcerative Colitis Patients Despite Low Serum Albumin Levels en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=IGAWAShoko en-aut-sei=IGAWA en-aut-mei=Shoko kn-aut-name=Ďq kn-aut-sei= kn-aut-mei=Ďq aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w 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=זERCCL2ɂᇊ֘A}Nt@[WWςx]ڑi@ kn-title=Osteosarcoma cell?derived CCL2 facilitates lung metastasis via accumulation of tumor-associated macrophages en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KONDOHiroya en-aut-sei=KONDO en-aut-mei=Hiroya kn-aut-name=ߓG kn-aut-sei=ߓ kn-aut-mei=G aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w 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=ǐVU牺gDւXڐAɂ鐶ы@\̉PF}EXfɂ錟 kn-title=Grafting Islets to a Prevascularized Subcutaneous Site to Improve Transplant Survival and Function: A Mouse Model en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OKADATsuyoshi en-aut-sei=OKADA en-aut-mei=Tsuyoshi kn-aut-name=c kn-aut-sei=c 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=Rww@㎕w 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=LRP4Agrin͓ϐɂĒ߂qg֐ߓזEɂ-JejVOi`BɊ֗^ kn-title=LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in -Catenin Signaling in Human Articular Chondrocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NANIWAShuichi en-aut-sei=NANIWA en-aut-mei=Shuichi kn-aut-name=QԐ kn-aut-sei=Q 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=Rww@㎕w 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=cɂe̋i͎qǂ̃AM[XN𑝉F21Iocf kn-title=Maternal smoking during infancy increases the risk of allergic disease in children: a nationwide longitudinal survey in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SHIGEHARAKenji en-aut-sei=SHIGEHARA en-aut-mei=Kenji kn-aut-name=Όi kn-aut-sei=Ό kn-aut-mei=i aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w 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=]fbgɂqgύRԎזEiSB623j̔]ڐAƐӉ^ы^̎Ì kn-title=Therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) with voluntary and forced exercise in a rat model of ischemic stroke en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NAGASETakayuki en-aut-sei=NAGASE en-aut-mei=Takayuki kn-aut-name=iV kn-aut-sei=i kn-aut-mei=V aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w 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=O]ǂ̍ČђʓIfF̔oє̌yxO]bǵA~NOÅAAXgOAǁAу^EIp`[𔺂sQN kn-title=Repeated non-hemorrhagic and non-contusional mild traumatic brain injury in rats elicits behavioral impairment with microglial activation, astrogliosis, and tauopathy: Reproducible and quantitative model of chronic traumatic encephalopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SUGAHARAChiaki en-aut-sei=SUGAHARA en-aut-mei=Chiaki kn-aut-name=疾 kn-aut-sei= kn-aut-mei=疾 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w 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=BǂݏQ̌`qiDYX1C1j̃bg]玿Bɂ鎞Ԕp^[ kn-title=Spatiotemporal expression pattern of dyslexia susceptibility 1 candidate 1 (DYX1C1) during rat cerebral cortex development en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ZENSHOKazumasa en-aut-sei=ZENSHO en-aut-mei=Kazumasa kn-aut-name=Ta^ kn-aut-sei=T kn-aut-mei=a^ aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=Rww@㎕w END start-ver=1.4 cd-journal=joma no-vol=55 cd-vols= no-issue=4 article-no= start-page=313 end-page=326 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review en-subtitle= kn-subtitle= en-abstract= kn-abstract=In recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability. Tropomyosin receptor kinase (TRK) inhibitors have shown considerable efficacy against tumors harboring neurotrophic receptor tyrosine kinase (NTRK) fusion genes, highlighting the growing importance of personalized medicine in cancer treatment. Advanced sequencing technologies enable the rapid analysis of numerous genetic abnormalities in tumors, facilitating the identification of patients with positive biomarkers. These advances have increased the likelihood of providing effective, tailored treatments. NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies. Consequently, the treatment outcomes for NTRK fusion-positive tumors have improved significantly, reflecting a shift toward more personalized therapeutic approaches. This review focuses on NTRK fusion-positive sarcomas and comprehensively evaluates their epidemiology, clinical features, and radiological and histological characteristics. We also investigated the treatment landscape, including the latest methodologies involving TRK inhibitors, and discussed the long-term efficacy of these inhibitors, and their optimal order of use. Notably, larotrectinib has demonstrated a high response rate in infantile fibrosarcoma, and its efficacy has been confirmed even in advanced cases. However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes. en-copyright= kn-copyright= en-aut-name=KubotaYuta en-aut-sei=Kubota en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawanoMasanori en-aut-sei=Kawano en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwasakiTatsuya en-aut-sei=Iwasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItonagaIchiro en-aut-sei=Itonaga en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakuNobuhiro en-aut-sei=Kaku en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TanakaKazuhiro en-aut-sei=Tanaka en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery , Science of Functional Recovery and Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= en-keyword=NTRK fusion-positive sarcoma kn-keyword=NTRK fusion-positive sarcoma en-keyword=larotrectinib kn-keyword=larotrectinib en-keyword=entrectinib kn-keyword=entrectinib en-keyword=infantile fibrosarcoma kn-keyword=infantile fibrosarcoma en-keyword=NTRK-rearranged spindle cell neoplasms kn-keyword=NTRK-rearranged spindle cell neoplasms END start-ver=1.4 cd-journal=joma no-vol=94 cd-vols= no-issue=11 article-no= start-page=3653 end-page=3665 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=Survey of Barley Sodium Transporter HvHKT1;1 Variants and Their Functional Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Barley (Hordeum vulgare L.) employs the Na+ transporter HvHKT1;1, which is an N+-selective transporter. This study characterized the full-length HvHKT1;1 (HvHKT1;1-FL) and three mRNA variants (HvHKT1;1-V1, -V2, and -V3), which encode polypeptides of 64.7, 54.0, 40.5, and 32.9 kDa, respectively. Tissue-specific expression profiling revealed that HvHKT1;1-FL is the most abundant transcript across leaf, sheath, and root tissues under normal conditions, with the highest expression in leaves. Under 150 mM NaCl stress, HvHKT1;1-FL and its variants showed a dynamic, time-dependent expression pattern, with peak leaf expression at 2 h, sheath expression at 12 h, and root expression at 2 h, suggesting their roles in early stress response. Functional analysis using two-electrode voltage-clamp measurements demonstrated that HvHKT1;1-FL is highly selective for Na+, with minimal conductance for K+, Li+, Rb+, or Cs+. It demonstrated high Na+ transport efficiency, characterized by higher Vmax and lower Km values, while the variants showed reduced Na+ currents, lower Vmax, and higher Km values, indicating decreased Na+ transport capacity. Reversal potential analyses further confirmed Na+ selectivity, with HvHKT1;1-FL displaying the strongest preference for Na+. Notably, while all variants retained Na+ selectivity, they showed reduced efficiency, as indicated by a more negative reversal potential in low Na+ conditions. These findings highlight the functional diversity among HvHKT1;1 variants, with HvHKT1;1-FL playing a dominant role in Na+ transport. The tissue-specific regulation of these variants under salinity stress underscores their importance in barleyfs adaptive responses. en-copyright= kn-copyright= en-aut-name=ImranShahin en-aut-sei=Imran en-aut-mei=Shahin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Department of Agronomy, Khulna Agricultural University kn-affil= en-keyword=Barley kn-keyword=Barley en-keyword=HvHKT1;1 kn-keyword=HvHKT1;1 en-keyword=Na+ transport kn-keyword=Na+ transport en-keyword=mRNA variants kn-keyword=mRNA variants en-keyword=TEVC kn-keyword=TEVC END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=42195 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elucidation of puberulic acid?induced nephrotoxicity using stem cell-based kidney organoids en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent cases of acute kidney injury (AKI) in Japan have been linked to Beni-koji CholesteHelp supplements, with puberulic acid identified as a potential nephrotoxic contaminant. To address the need for a reliable in vitro nephrotoxicity testing platform, we developed a screening model using kidney organoids derived from adult rat kidney stem (KS) cells. The organoids were exposed to known nephrotoxicants, including cisplatin and gentamicin, to validate the system. Puberulic acid toxicity was evaluated in both KS cell-derived organoids and wild-type mice. The organoids recapitulated tubular injury induced by known nephrotoxins and showed significant Kim-1 mRNA upregulation. Puberulic acid-treated organoids and mice exhibited morphological features of acute tubular necrosis (ATN), mitochondrial damage, and reduced cytochrome c oxidase subunit IV (COX-IV) expression. Markers of oxidative stress and apoptosis, such as 8-hydroxy-2f-deoxyguanosine (8-OHdG) and cleaved caspase-3, were also elevated. These findings suggest that puberulic acid induces mitochondrial dysfunction and oxidative stress, leading to tubular cell death. Puberulic acid-induced nephrotoxicity was demonstrated using our kidney organoid model. KS cell-derived kidney organoids may provide a simple, reproducible, and rapid platform for nephrotoxicity assessment, which may complement conventional animal experiments. 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=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Kidney organoid kn-keyword=Kidney organoid en-keyword=Kidney stem cell kn-keyword=Kidney stem cell en-keyword=Puberulic acid kn-keyword=Puberulic acid en-keyword=Nephrotoxicity kn-keyword=Nephrotoxicity en-keyword=Mitochondrial dysfunction kn-keyword=Mitochondrial dysfunction END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=5 article-no= start-page=e70057 end-page= 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=A Case of IgA Nephropathy With Membranoproliferative Glomerulonephritis-Like Features Miyu Kanazawa, en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 73-year-old man was referred due to the onset of nephrotic-range proteinuria. He had been diagnosed with rheumatoid arthritis 18?years prior and had achieved remission with treatment, including methotrexate and janus kinase (JAK) inhibitor. Although routine follow-ups had not revealed any urinary abnormalities, subsequent tests detected proteinuria and hematuria in the absence of infection or other symptoms. As the urinary abnormalities persisted, with a serum albumin decrease and proteinuria measuring 5.7?g/day, indicating nephrotic syndrome, the patient was referred to our hospital for further evaluation, and a renal biopsy was performed. Light microscopy revealed mesangial cell proliferation, endocapillary proliferation and double-contoured basement membranes. Immunofluorescence microscopy showed IgA-dominant deposits in both mesangial areas and glomerular capillary walls. Transmission electron microscopy demonstrated electron-dense deposits in the mesangium and subendothelial regions, leading to the diagnosis of membranoproliferative glomerulonephritis (MPGN)-type IgA nephropathy. Immunostaining with the Gd-IgA1 (galactose-deficient IgA1)-specific antibody (KM55) was positive, consistent with the diagnosis. Following the initiation of steroid therapy, proteinuria rapidly decreased, achieving complete remission within 5?months. IgA nephropathy with MPGN-like features often presents as nephrotic syndrome, differing from the typical pathological and clinical presentation of IgA nephropathy, making differentiation from secondary MPGN and other diseases sometimes challenging. This case suggests that KM55 staining may offer additional information in differentiating atypical IgA nephropathy with non-classical pathological features. en-copyright= kn-copyright= en-aut-name=KanazawaMiyu en-aut-sei=Kanazawa en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=AokiRyoya en-aut-sei=Aoki en-aut-mei=Ryoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SueMihiro en-aut-sei=Sue en-aut-mei=Mihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyakeHiromasa en-aut-sei=Miyake en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= affil-num=1 en-affil=Okayama University Medical School 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=Okayama University Medical School 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 Chronic Kidney Disease and Cardiovascular Disease, 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= en-keyword=Gd-IgA1 kn-keyword=Gd-IgA1 en-keyword=IgA nephropathy kn-keyword=IgA nephropathy en-keyword=membranoproliferative glomerulonephritis kn-keyword=membranoproliferative glomerulonephritis en-keyword=nephrotic syndrome kn-keyword=nephrotic syndrome en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=5762 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hypoglycemia and hyperinsulinemia induced by phenolic uremic toxins in CKD and DKD patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Patients with end-stage renal disease have lower fasting plasma glucose and HbA1c levels, with significantly higher insulin levels. For a long time, it has been believed that this higher insulin level in renal failure is due to decreased insulin clearance caused by reduced renal function. However, here we reported that accumulation of the gut microbiota-derived uremic toxin, phenyl sulfate (PS) in the renal failure, increased insulin secretion from the pancreas by enhanced glucose-stimulated insulin secretion. Other endogenous sulfides compounds which accumulated as in the renal failure also increased glucose-stimulated insulin secretion from ?-cell. With RNA-seq analyses and gene knock down, we demonstrated that insulin secretion evoked by PS was mediated by Ddah2. In addition, we also found that PS increased insulin resistance through lncRNA expression and Erk phosphorylation in the adipocytes. To confirm the relationship between PS and glucose metabolism in human, we recruited 2 clinical cohort studies (DKD and CKD) including 462 patients, and found that there was a weak negative correlation between PS and HbA1c. Because these trials did not measure fasting insulin level, we alternatively used the urinary C-peptide/creatinine ratio (UCPCR) as an indicator of insulin resistance. We found that PS may induce insulin resistance in patients with eGFR? Methods: Fourteen MDA5-DM patients with multiple adverse prognostic factors were studied. Seven received the BRT-Tx regimen, and the remaining seven, previously treated with TC-Tx, served as historical controls. Twelve-month survival was assessed. Transcriptome analysis was performed for six patients (BRT=3, TC=3), beginning with cluster analysis to evaluate whether changes in peripheral blood gene expression varied according to treatment or prognosis. Gene ontology analysis characterized expression profiles in survivors and distinguished treatment effects. Alterations in the type I, II, and III interferon signatures were also assessed.
Results: In the TC-Tx group, four of seven patients succumbed to RP-ILD, whereas all seven BRT-Tx patients survived the 12-month observation period. Only one BRT-Tx patient required combined rescue therapies, including plasma exchange, and one case of unexplained limbic encephalitis (LE) occurred. Cytomegalovirus reactivation was observed in both groups (BRT: 5/7; TC: 6/7). Transcriptomic analysis revealed no treatment-specific clustering of differentially expressed genes (DEGs) before and after therapy. However, survivors and nonsurvivors formed distinct clusters, with survivors showing significant posttreatment suppression of B-cell-related gene expression. Moreover, interferon signature scores were significantly lower after treatment in survivors than in nonsurvivors. BRT-Tx effectively suppressed B-cell-mediated immune responses and maintained a low interferon signature, while TC-Tx resulted in nonspecific gene suppression, and in nonsurvivors, an elevated interferon signature was observed.
Conclusion: BRT-Tx has the potential to improve survival in MDA5-DM patients by effectively targeting hyperactive immune pathways. The combination of rituximab and tacrolimus is expected to disrupt B-cell?T-cell interactions and reduce autoantibody production, whereas baricitinib may suppress both IFN and GM-CSF signaling, regulating excessive autoimmunity mediated by cells such as macrophages. Unlike TC-Tx, BRT-Tx avoids cyclophosphamide-associated risks such as infertility and secondary malignancies. Future randomized controlled trials are warranted to validate its efficacy and safety. en-copyright= kn-copyright= en-aut-name=TokunagaMoe en-aut-sei=Tokunaga en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaiYu en-aut-sei=Nakai en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoYoshiharu en-aut-sei=Sato en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiratsukaMitori en-aut-sei=Hiratsuka en-aut-mei=Mitori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=NakatsueTakeshi en-aut-sei=Nakatsue en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaekiTakako en-aut-sei=Saeki en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmayaharaTakatsune en-aut-sei=Umayahara en-aut-mei=Takatsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=KoyamaYoshinobu en-aut-sei=Koyama en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital kn-affil= affil-num=3 en-affil=DNA Chip Research Inc., Medical Laboratory kn-affil= affil-num=4 en-affil=DNA Chip Research Inc., Medical Laboratory 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=Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital kn-affil= affil-num=7 en-affil=Division of Rheumatology and Nephrology, Department of Internal Medicine, Nagaoka Red Cross Hospital kn-affil= affil-num=8 en-affil=Division of Dermatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital 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=Division of Rheumatology, Center for Autoimmune Diseases, Japanese Red Cross Okayama Hospital kn-affil= en-keyword=anti-MDA5 antibody-positive dermatomyositis (MDA5-DM) kn-keyword=anti-MDA5 antibody-positive dermatomyositis (MDA5-DM) en-keyword=JAK inhibitor kn-keyword=JAK inhibitor en-keyword=baricitinib kn-keyword=baricitinib en-keyword=rituximab kn-keyword=rituximab en-keyword=multitargeted treatment kn-keyword=multitargeted treatment en-keyword=IFN signature kn-keyword=IFN signature en-keyword=transcriptome analysis kn-keyword=transcriptome analysis 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=17 cd-vols= no-issue=10 article-no= start-page=e94951 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251019 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bladder Trigone as a Sensory Hub: A Narrative Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=The bladder trigone is an anatomically and functionally distinct region within the lower urinary tract (LUT), characterized by a dense network of afferent sensory fibers, specialized urothelial interactions, and prominent mechanotransduction mechanisms. Its intricate neuroarchitecture enables precise detection of bladder filling and coordination of micturition, whereas dysregulation of these pathways contributes to lower urinary tract symptoms (LUTS), including urgency, frequency, and bladder pain. Despite its recognized clinical relevance, the structural and functional basis of trigonal sensory signaling - and its role - remain incompletely understood.
This review synthesizes current evidence on trigonal afferent organization, integrating data from anatomical mapping, receptor profiling, electrophysiological characterization, and translational research. Seminal anatomical observations are combined with recent advances in mechanotransduction and purinergic, peptidergic, and transient receptor potential (TRP) signaling to provide a comprehensive perspective. The trigone exhibits three principal afferent classes: (1) intraepithelial fibers penetrating umbrella cells, marked by P2X purinoceptor 3 (P2X3), transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP), and substance P (SP); (2) subepithelial plexuses surrounding microvasculature, enriched in vasoactive neuropeptides and exhibiting plastic hypertrophy in overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS); and (3) encapsulated corpuscular endings at the lamina propria-detrusor junction, expressing PIEZO1/2 and acid-sensing ion channels (ASICs) for rapid adaptation. In trigeminal dorsal root ganglion (DRG) neurons, high expression of PIEZO2, P2RX3, and voltage-gated sodium channel, type 1.8 (Nav1.8) was observed, revealing their role as the foundation for multisensory information processing. Functional assays highlight distinct mechanotransductive and chemosensory pathways, with aging, inflammation, and neurotrophic factors driving afferent plasticity underlying abnormal bladder sensation, such as urgency, frequency, and pain. Early clinical trials of P2X3 antagonists and intravesical TRPV1 inhibitors demonstrate promising symptomatic benefits. Collectively, evidence positions the bladder trigone as a critical sensory hub where neuronal, urothelial, and immune signals converge to regulate bladder sensation. Understanding its molecular and structural specialization may inform the development of region-specific neuromodulatory therapies targeting sensory urgency and afferent-driven bladder dysfunction. en-copyright= kn-copyright= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeTomofumi en-aut-sei=Watanabe en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=bladder trigone kn-keyword=bladder trigone en-keyword=botulinum toxin kn-keyword=botulinum toxin en-keyword=lower urinary tract symptoms kn-keyword=lower urinary tract symptoms en-keyword=sensory afferents kn-keyword=sensory afferents en-keyword=varicosities kn-keyword=varicosities END start-ver=1.4 cd-journal=joma no-vol=786 cd-vols= no-issue= article-no= start-page=152753 end-page= 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=Hydrogen-rich gas enhances mitochondrial membrane potential and respiratory function recovery in Caco-2 cells post-ischemia-reperfusion injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Ischemia-reperfusion (I/R) injury induces oxidative stress, leading to damage in highly susceptible intestinal tissues. Molecular hydrogen (H2) has shown therapeutic potential in I/R injuries, with our prior research showing its efficacy in improving outcomes in rat intestinal transplantation models. However, its impact on mitochondrial function remain insufficiently understood. This study aims to elucidate how H2 modulates mitochondrial function impaired by I/R injury.
Methods: To assess the effects of H2 on I/R injury, cells were divided into three groups: a control group, a hypoxic group (99 % N2, 1 % O2, without H2 for 3, 6, or 24 h), and a hypoxic-H2 group (99 % H2, 1 % O2, for the same durations). After treatment, cells were reoxygenated under normoxic conditions (21 % O2) for 1, 2, 4, or 6 h. Mitochondrial membrane potential, oxygen consumption, and ATP production were measured. Reactive oxygen species production and apoptotic and metabolic regulators were also assessed.
Results: H2 markedly promoting mitochondrial recovery following I/R injury, by enhancing ATP production, restoring mitochondrial membrane potential, and improving oxygen consumption. It also reduced ROS levels and suppressed pro-apoptotic signaling. Notably, H2 suppressed the expression of HIF1 and PDK1, suggesting that H2 may act upstream of hypoxia-driven signaling pathways. These changes promoted oxidative phosphorylation and overall cellular function during reperfusion.
Conclusions: Our findings reveal that H2 therapy supports mitochondrial function, suppresses ROS, and modulates hypoxia-driven pathways in I/R injury. These insights advance the understanding of H2's potential in addressing I/R injury and provide a foundation for its application in other hypoxia-related conditions. en-copyright= kn-copyright= en-aut-name=SeyaMizuki en-aut-sei=Seya en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MengYing en-aut-sei=Meng en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinoriKosaki en-aut-sei=Yoshinori en-aut-mei=Kosaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=WatanabeAkihiro en-aut-sei=Watanabe en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaTaihei en-aut-sei=Yamada en-aut-mei=Taihei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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, Disaster and Critical Care Medicine, Hyogo Medical University kn-affil= affil-num=10 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University 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= affil-num=12 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Intestinal ischemia-reperfusion injury kn-keyword=Intestinal ischemia-reperfusion injury en-keyword=Molecular hydrogen kn-keyword=Molecular hydrogen en-keyword=Hydrogen gas therapy kn-keyword=Hydrogen gas therapy en-keyword=Caco-2 cells kn-keyword=Caco-2 cells en-keyword=Mitochondrial function kn-keyword=Mitochondrial function en-keyword=Hypoxia-inducible factor-1 (HIF1) kn-keyword=Hypoxia-inducible factor-1 (HIF1) END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=1 article-no= start-page=e70221 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pediatric stroke risk and neurotrauma from roller coasters in amusement parks en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although rare, neurotrauma has been documented as a potential risk of high-speed, high-acceleration amusement park rides such as roller coasters. These attractions generate rapid acceleration, deceleration, sharp turns, and significant gravitational forces, which may stress the central nervous system and cerebrovascular structures. This review analyzed pediatric stroke cases (children 15?years old or younger) linked to roller-coaster rides reported in PubMed and summarized the key mechanisms and clinical features associated with such neurotrauma. Documented complications include internal and vertebral carotid artery dissections, with or without stroke, subdural hemorrhage, intraparenchymal hemorrhage, and post-traumatic migraines. The aim of this review is to alert healthcare providers to the possibility of stroke induced by roller-coaster rides, emphasizing the importance of timely diagnosis and management to prevent adverse outcomes. Key considerations include the recognition of risk factors, public education on potential risks, and strategies for preventing complications in at-risk populations. Although intracranial hemorrhage from roller-coaster rides is rare, individuals with predisposing conditions, such as prior head trauma or vascular abnormalities, should be evaluated carefully when presenting with neurological symptoms after such activities. en-copyright= kn-copyright= en-aut-name=MorikawaTomoki en-aut-sei=Morikawa en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TokiokaKohei en-aut-sei=Tokioka en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=amusement parks kn-keyword=amusement parks en-keyword=brain injuries kn-keyword=brain injuries en-keyword=carotid artery dissection kn-keyword=carotid artery dissection en-keyword=stroke kn-keyword=stroke en-keyword=vertebral artery dissection kn-keyword=vertebral artery dissection END start-ver=1.4 cd-journal=joma no-vol=254 cd-vols= no-issue= article-no= start-page=108998 end-page= 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=Cellulose nanofibers boost soil water availability, plant growth, and irrigation water use efficiency under deficit irrigation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Under climate change, even previously rainfall-prone areas may experience droughts, and effective strategies are vital for soil conservation. Owing to their cutting-edge water absorption and storage properties, cellulose nanofibers (CNF) are expected to increase soil water availability and help plants resist water stress. However, the role of CNF in improving plant growth and soil water retention under various irrigation regimes is not yet known. We evaluated the effects of CNFs on plant available water (PAW), germination, plant growth, and irrigation water use efficiency (IWUE) under both adequate and deficit irrigation conditions. Plant cultivation experiments were conducted using different CNF dosages (0%, 0.1%, 0.5%, and 1.0%), irrigation levels (I100, I50, and I25), and soil types (sandy and silty loam). The results indicated that CNF significantly increased field capacity (FC) and PAW in both soil types, with PAW in CNF-amended soils increasing by up to 110% and 88% in sandy and silty loam soil, respectively, at 1% CNF dosage. In germination tests, CNF showed no phytotoxicity and supported the germination process during water stress, with enhancements of up to 64% and 163% at I50 and up to 125% and 214% at I25 in germination percentage and germination index, respectively. Plant growth experiments revealed that CNF addition helped plants resist water stress, maintaining plant height and weight close to those under full irrigation, while using 50% less water. IWUE analyses demonstrated that CNF enhanced IWUE, with increases of up to 56% under sufficient watering (I100), 169% under moderate water stress (I50), and 120% under severe water stress (I25), at 1% CNF dosage. These findings highlight the potential of CNF as a multifaceted amendment, offering practical solutions for addressing water scarcity challenges and contributing to more resilient and sustainable agricultural practices. en-copyright= kn-copyright= en-aut-name=NgoAn Thuy en-aut-sei=Ngo en-aut-mei=An Thuy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NguyenManh Cong en-aut-sei=Nguyen en-aut-mei=Manh Cong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaedaMorihiro en-aut-sei=Maeda en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriYasushi en-aut-sei=Mori en-aut-mei=Yasushi 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=Nong Lam University kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Cellulose nanofibers kn-keyword=Cellulose nanofibers en-keyword=Available water kn-keyword=Available water en-keyword=Plant growth kn-keyword=Plant growth en-keyword=Irrigation water use efficiency kn-keyword=Irrigation water use efficiency en-keyword=Deficit irrigation kn-keyword=Deficit irrigation en-keyword=Water stress kn-keyword=Water stress END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=2 article-no= start-page=650 end-page=653 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful Transplantation of Multiple Organs from Donor after Helium Asphyxiation: First Case Report in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Helium inhalation has increased, but most cases are either minor injuries or deaths; there have not yet been any reported cases of brain death leading to organ donation. We report a patient who attempted helium inhalation and was declared brain dead and became an organ donor without complications. To the best of our knowledge, this is the first reported case of deceased organ donation following helium asphyxiation in Japan. The patient in cardiac arrest was found with a helium-filled vinyl bag sealed around the neck. During emergency medical transport to the hospital, a spontaneous return of circulation was obtained after 31 minutes of cardiopulmonary resuscitation. Upon hospital arrival, the physical examination revealed dilated pupils with no response to light. Electrocardiography showed widespread ST-segment depression and ST-segment elevation in augmented Vector Right, as well as elevated cardiac enzymes and decreased myocardial contractility. Head computed tomography revealed diffuse cerebral edema and loss of the gray-white matter boundary without signs of air embolism in the cerebral and coronary arteries. Despite comprehensive post-cardiac arrest care with recovery of organ function, brain death was confirmed on day 4 after hospitalization. The family consented to organ donation on the 11th day of hospitalization. The heart, lungs, liver, and two kidneys were successfully transplanted and all organs functioned. All organ grafts were functioning well at the 3-month follow-up. Our case demonstrates that brain death caused by helium inhalation is not a contraindication to organ donation. en-copyright= kn-copyright= en-aut-name=JinnoShunta en-aut-sei=Jinno en-aut-mei=Shunta 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=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=brain death kn-keyword=brain death en-keyword=heart arrest kn-keyword=heart arrest en-keyword=helium kn-keyword=helium END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=185 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tattoo-associated toxic shock syndrome: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Toxic shock syndrome (TSS) is a rare but life-threatening complication occasionally reported after tattooing.
Case presentation: : A 29-year-old Japanese man was admitted to Okayama University Hospital, Okayama, Japan, in early spring 2025, one week after receiving a tattoo on his right shoulder and upper arm in Osaka. He presented with fever, gastrointestinal symptoms, hypotension, and multi-organ failure. Despite a failure to isolate a causative pathogen, he met clinical criteria for TSS. Supportive care and broad-spectrum antibiotics led to full recovery.
Conclusions: TSS can occur after tattooing, even in individuals without apparent immunodeficiency. Pathogenic organisms may be unidentifiable; however, clinical diagnosis should not be delayed, and early therapeutic interventions are essential to improve outcomes. en-copyright= kn-copyright= en-aut-name=KuboTakuya en-aut-sei=Kubo en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=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= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Blood culture kn-keyword=Blood culture en-keyword=Critically ill kn-keyword=Critically ill en-keyword=Septic shock kn-keyword=Septic shock en-keyword=Tattooing kn-keyword=Tattooing en-keyword=Toxic shock syndrome kn-keyword=Toxic shock syndrome END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=18 article-no= start-page=1481 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Oral Peritumoral Tissue on Infiltration and Differentiation of Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=The recruitment of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) of oral squamous carcinoma (OSCC) affects significant cancer invasion; however, in the normal host tissue that is located in the cancerfs surrounding area, this is poorly investigated. In this study, we examined the impact of gingival connective tissue cells (GCTCs) and periodontal ligament cells (PDLCs), which are involved in the invasive pathway of OSCC, on oral cancer invasion via TAMs recruitment. Transwell (migration) assays were used to examine the effects of GCTCs and PDLCs on the migration of macrophages, which indicated that the interaction between GCTCs and HSC-2/HSC-3 (human oral squamous cell carcinoma cell line) promoted the recruitment of macrophages, whereas the interaction between PDLCs was inhibited. An indirect co-culture was then used to examine the effects of GCTCs and PDLCs on the differentiation of macrophages, which indicated that the interaction between GCTCs enhanced their ability to transform into M2-type macrophages. Furthermore, the effects of GCTCs and PDLCs on the recruitment of CD45(+) monocytes, F4/80(+) M0 macrophages, iNOS(+) M1 macrophages, and CD163(+) M2 TAMs were assayed by immunohistochemistry. The results revealed that the interaction between GCTCs and HSC-2/HSC-3 promoted the infiltration of CD45(+) monocytes, F4/80(+) M0 macrophages, and CD163(+) M2 TAMs, whereas the PDLCs inhibited it, while their effect on iNOS(+) M1 macrophages was limited. Collectively, the GCTCs contributed to the infiltration of TAMs into the TME of OSCC cells, whereas the PDLCs exerted an inhibitory effect. These findings suggest a potential regulatory mechanism underlying the progression of OSCC. en-copyright= kn-copyright= en-aut-name=PiaoTianyan en-aut-sei=Piao en-aut-mei=Tianyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ArashimaTakuma en-aut-sei=Arashima en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhaoYulu en-aut-sei=Zhao en-aut-mei=Yulu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MinZin Zin en-aut-sei=Min en-aut-mei=Zin Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=oral squamous cell carcinoma (OSCC) kn-keyword=oral squamous cell carcinoma (OSCC) en-keyword=gingival connective tissue cells (GCTCs) kn-keyword=gingival connective tissue cells (GCTCs) en-keyword=periodontal ligament cells (PDLCs) kn-keyword=periodontal ligament cells (PDLCs) en-keyword=tumor-associated macrophages (TAMs) kn-keyword=tumor-associated macrophages (TAMs) en-keyword=macrophage polarity kn-keyword=macrophage polarity en-keyword=tumor microenvironment (TME) kn-keyword=tumor microenvironment (TME) END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=17 article-no= start-page=2770 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250825 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Refining the Role of Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the tumor microenvironment, various immune and stromal cells, such as fibroblasts and vascular endothelial cells, contribute to tumor growth and progression by interacting with cancer cells. Tumor-associated macrophages (TAMs) have attracted attention as major players in the tumor microenvironment. The origin of TAMs is believed to be the infiltration of monocytes derived from bone marrow progenitor cells into tumor tissues and their differentiation into macrophages, whereas tissue-resident macrophages derived from yolk sacs have recently been reported. TAMs infiltrating tumor tissues act in a tumor-promoting manner through immunosuppression, angiogenesis, and the promotion of cancer cell invasion. Reflecting the nature of TAMs, increased TAM invasion and TAM-specific gene expression in tumor tissues may be the new biomarkers for cancer. Moreover, new therapeutic strategies targeting TAMs, such as transformation into immunostimulatory macrophages, suppression of TAM infiltration, and promotion of phagocytosis, are being investigated, and many clinical trials are underway. As the origin and function of TAMs are further elucidated, TAM-targeted therapy is expected to become a new option for the immunotherapy of various cancers, including oral cancers. en-copyright= kn-copyright= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TianyanPiao en-aut-sei=Tianyan en-aut-mei=Piao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ArashimaTakuma en-aut-sei=Arashima en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChangAnqi en-aut-sei=Chang en-aut-mei=Anqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MinZin Zin en-aut-sei=Min en-aut-mei=Zin Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiMasae en-aut-sei=Fujii en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=tumor-associated macrophage (TAM) kn-keyword=tumor-associated macrophage (TAM) en-keyword=oral squamous cell carcinoma (OSCC) kn-keyword=oral squamous cell carcinoma (OSCC) en-keyword=macrophage polarity kn-keyword=macrophage polarity en-keyword=invasion kn-keyword=invasion en-keyword=carcinogenesis kn-keyword=carcinogenesis END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=14 article-no= start-page=4055 end-page=4070 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CXCR4 Inhibition Induces Tumor Necrosis by Selectively Targeting the Proliferating Blood Vessels in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=The C-X-C chemokine receptor type 4 (CXCR4) is a G protein-coupled transmembrane receptor that contributes to tumor growth and angiogenesis. While prior studies have primarily focused on CXCR4 expression in cancer cells and its role in metastasis, a few have examined its involvement in tumor-associated vasculature. In this study, we reported for the first time that CXCR4 expression within the tumor vasculature is significantly associated with higher pathological grades of human oral squamous cell carcinoma (OSCC) (p<0.03). A previous study reported that inhibiting CXCR4 with AMD3100 induces tumor cell death and enhances the efficacy of the chemotherapeutic agent cisplatin. These findings suggest that CXCR4 is an important target for cancer treatment. However, the tumor vascular system is known to be heterogeneous within the tumor microenvironment (TME), which may influence the treatment outcomes. Therefore, this study aimed to explore the effect of CXCR4 antagonism on various blood vessels present within the oral squamous cell carcinoma (OSCC) tumor stroma. Although the efficiency of AMD3100 was not significant in MOC cancer cells, necrosis was induced in the TME when applied to a poorly differentiated OSCC model, highlighting the role of the TME. Notably, CXCR4 is found to be highly overlapped with CD105+ angiogenic tumor vessels among various vascular markers. Treatment with AMD3100 leads to a marked reduction in the CD105+ vessels and impairs the maturation of tumor micro-vessels, explaining the cause of observed necrosis. Thus, CXCR4 serves as a promising biomarker in OSCC, and its inhibition with AMD3100 offers the therapeutic potential, particularly in cases with advanced pathological grades. en-copyright= kn-copyright= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaSaori en-aut-sei=Yoshida en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MinZin Zin en-aut-sei=Min en-aut-mei=Zin Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Preliminary Examination Room, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= en-keyword=CXCR4 kn-keyword=CXCR4 en-keyword=tumor angiogenesis kn-keyword=tumor angiogenesis en-keyword=chemokine receptors kn-keyword=chemokine receptors en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=oral squamous cell carcinoma (OSCC) kn-keyword=oral squamous cell carcinoma (OSCC) en-keyword=AMD3100 kn-keyword=AMD3100 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e64296 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Giant Choledochal Cyst in a Child With Spinocerebellar Ataxia: A Potential Molecular Link Through Aberrant Cytosolic Calcium Signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SumitomoHiromi en-aut-sei=Sumitomo en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanameTadashi en-aut-sei=Kaname en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakenouchiToshiki en-aut-sei=Takenouchi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Genome Medicine, National Center for Child Health and Development kn-affil= affil-num=4 en-affil=Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=calcium signaling kn-keyword=calcium signaling en-keyword=cerebellar ataxia 29 kn-keyword=cerebellar ataxia 29 en-keyword=cerebellar atrophy kn-keyword=cerebellar atrophy en-keyword=choledochal cyst kn-keyword=choledochal cyst en-keyword=congenital biliary dilatation kn-keyword=congenital biliary dilatation en-keyword=inositol 1,4,5-trisphosphate receptors kn-keyword=inositol 1,4,5-trisphosphate receptors en-keyword=ITPR1 kn-keyword=ITPR1 END start-ver=1.4 cd-journal=joma no-vol=2025 cd-vols= no-issue=1 article-no= start-page=e240121 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adult hypophosphatasia presenting with recurrent acute joint pain en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms. en-copyright= kn-copyright= en-aut-name=YoshidaHayao en-aut-sei=Yoshida en-aut-mei=Hayao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurakamiTakaaki en-aut-sei=Murakami en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OgawaAtsubumi en-aut-sei=Ogawa en-aut-mei=Atsubumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SunouchiTakashi en-aut-sei=Sunouchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HidakaNaoko en-aut-sei=Hidaka en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoNobuaki en-aut-sei=Ito en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurakamiHiromi en-aut-sei=Murakami en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawasakiHidenori en-aut-sei=Kawasaki en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakajimaKatsumi en-aut-sei=Nakajima en-aut-mei=Katsumi 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=YamamotoTaizo en-aut-sei=Yamamoto en-aut-mei=Taizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Diabetes and Endocrinology, Shiga General Hospital kn-affil= affil-num=2 en-affil=Department of Diabetes and Endocrinology, Shiga General Hospital kn-affil= affil-num=3 en-affil=Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Division of Nephrology and Endocrinology, The University of Tokyo Hospital kn-affil= affil-num=5 en-affil=Division of Nephrology and Endocrinology, The University of Tokyo Hospital kn-affil= affil-num=6 en-affil=Osteoporosis Center, The University of Tokyo Hospital kn-affil= affil-num=7 en-affil=Department of Genomic Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Genomic Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Diabetes and Endocrinology, Shiga General Hospital kn-affil= affil-num=11 en-affil=Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Diabetes and Endocrinology, Shiga General Hospital kn-affil= en-keyword=hypophosphatasia kn-keyword=hypophosphatasia en-keyword=genetic disorders kn-keyword=genetic disorders en-keyword=bone kn-keyword=bone END start-ver=1.4 cd-journal=joma no-vol=122 cd-vols= no-issue=5 article-no= start-page=689 end-page=699 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cytomegalovirus reactivation in patients with large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chimeric antigen receptor (CAR) T-cell therapy has improved outcomes of relapsed and/or refractory large B-cell lymphoma (r/r LBCL). However, its off-tumor effects result in severe prolonged humoral immune deficiency. Cytomegalovirus (CMV) is a latent virus that can be life-threatening in immunosuppressed patients. In the setting of CAR T-cell therapy, Asian race is a risk factor for clinically significant CMV infection. However, the effect of CAR T-cell therapy on CMV reactivation in Japanese patients remains unclear. Previous reports used polymerase chain reaction (PCR), but we used the pp65 antigenemia assay to retrospectively investigate long-term effects in patients with r/r LBCL. The study included 46 patients. Nine (19.6%) developed CMV reactivation, with a median onset of 13 days. Six of these patients received preemptive therapy, and none developed CMV end-organ disease. Primary refractory disease, grade 2?4 cytokine release syndrome, and high-dose corticosteroids were risk factors for CMV reactivation. Long-term follow-up showed that CMV reactivation rarely occurred later than 28 days post-infusion. Our study using the pp65 antigenemia assay showed a similar incidence of CMV reactivation, onset, and risk factors to those in the previous reports using PCR. en-copyright= kn-copyright= en-aut-name=HayashinoKenta en-aut-sei=Hayashino en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MasunariTaro en-aut-sei=Masunari en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashidaRisa en-aut-sei=Hashida en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkaSatoshi en-aut-sei=Oka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraYuki en-aut-sei=Fujiwara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KamoiChihiro en-aut-sei=Kamoi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=3 en-affil=Department of Hematology, Chugoku Central Hospital kn-affil= affil-num=4 en-affil=Division of Hematology, Ehime Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Science Center kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=16 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= en-keyword=Cytomegalovirus reactivation kn-keyword=Cytomegalovirus reactivation en-keyword=Large B-cell lymphoma kn-keyword=Large B-cell lymphoma en-keyword=CAR T-cell therapy kn-keyword=CAR T-cell therapy en-keyword=Hypogammaglobulinemia kn-keyword=Hypogammaglobulinemia 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=20251019 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of methotrexate-dosing regimens for GVHD prophylaxis on clinical outcomes of HLA-matched allogeneic HSCT en-subtitle= kn-subtitle= en-abstract= kn-abstract=Severe graft-versus-host disease (GVHD) remains a major complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT), necessitating optimal immunosuppressive strategies. This retrospective study used data from the Japanese Transplant Registry Unified Management Program to compare three methotrexate (MTX)-dosing regimens for GVHD prophylaxis in patients undergoing human leucocyte antigen (HLA)-matched allo-HSCT: a low-dose 3-day regimen (Ld3:10?mg/m2 on day 1, 7?mg/m2 on days 3 and 6), a low-dose 4-day regimen (Ld4: Ld3 with an additional 7?mg/m2 on day 11) and an original-dose 3-day regimen (Od3: 15?mg/m2 on day 1, 10?mg/m2 on days 3 and 6). Among 2537 analysed patients, Ld3 was the most commonly used regimen. Multivariate analyses showed no significant differences in the cumulative incidence of grade II?IV acute GVHD among regimens. However, Od3 was associated with an increased risk of grade III?IV acute GVHD, and Ld4 was linked to delayed neutrophil engraftment. This study is the first large-scale retrospective analysis of the impact of different MTX-dosing regimens on the outcomes of HLA-matched allo-HSCT, providing valuable insights into optimal MTX-dosing strategies in clinical practice. en-copyright= kn-copyright= en-aut-name=SuzukiTomotaka en-aut-sei=Suzuki en-aut-mei=Tomotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JoTomoyasu en-aut-sei=Jo en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshifujiKota en-aut-sei=Yoshifuji en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTadakazu en-aut-sei=Kondo en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishidaTetsuya en-aut-sei=Nishida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OnishiYasushi en-aut-sei=Onishi en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SawaMasashi en-aut-sei=Sawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HasegawaYuta en-aut-sei=Hasegawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SerizawaKentaro en-aut-sei=Serizawa en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OtaShuichi en-aut-sei=Ota en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YoshimitsuMakoto en-aut-sei=Yoshimitsu en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=3 en-affil=Department of Hematology, Institute of Science Tokyo kn-affil= affil-num=4 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=5 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital kn-affil= affil-num=6 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Centre kn-affil= affil-num=7 en-affil=Department of Hematology, Japanese Red Cross Aichi Medical Centre Nagoya Daiichi Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Tohoku University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Haematopoietic Stem Cell Transplantation, National Cancer Centre Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Anjo Kosei Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Sapporo Hokuyu Hospital kn-affil= affil-num=15 en-affil=Department of Hematology, Kanagawa Cancer Centre kn-affil= affil-num=16 en-affil=Department of Hematology and Rheumatology, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=17 en-affil=Japanese Data Centre for Haematopoietic Cell Transplantation kn-affil= affil-num=18 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=allo-HSCT kn-keyword=allo-HSCT en-keyword=dosing regimens kn-keyword=dosing regimens en-keyword=graft-versus-host disease kn-keyword=graft-versus-host disease en-keyword=GVHD prophylaxis kn-keyword=GVHD prophylaxis en-keyword=methotrexate kn-keyword=methotrexate END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=5 article-no= start-page=e70138 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Late]Onset?Invasive Aspergillosis With Pituitary Involvement and Dysfunction Following CD19 Chimeric Antigen Receptor T]Cell Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Invasive fungal infection (IFI) after chimeric antigen receptor (CAR) T-cell therapy is less common than bacterial and viral infections, but can be fatal once it develops. As most cases occur within 30 days after CAR T-cell infusion, late-onset IFI?particularly mould infection?appears to be under-recognised.
Discussion: We report an illustrative case of pituitary aspergillosis developing as late as one year after CD19 CAR T-cell therapy, highlighting a persistent risk in certain patients with delayed immune reconstitution.
Conclusion: This case underscores the need for continued vigilance and individualised antifungal strategies to prevent IFI beyond the early post-infusion period.
Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission. en-copyright= kn-copyright= en-aut-name=IkedaDaisuke en-aut-sei=Ikeda en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NawadaTomohiro en-aut-sei=Nawada en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinoharaTakayuki en-aut-sei=Shinohara en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaganoTomohiro en-aut-sei=Nagano en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KubotaSaya en-aut-sei=Kubota en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiyamaRyuichiro en-aut-sei=Hiyama en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoMasaya en-aut-sei=Ueno en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MakitaMasanori en-aut-sei=Makita en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=The Center for Graduate Medical Education, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Fungal Infection, National Institute of Infectious Diseases kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Chugoku Central Hospital kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=aspergillosis kn-keyword=aspergillosis en-keyword=CD19 CAR T kn-keyword=CD19 CAR T en-keyword=invasive fungal infection kn-keyword=invasive fungal infection en-keyword=pituitary kn-keyword=pituitary END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=18 article-no= start-page=4640 end-page=4653 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC en-subtitle= kn-subtitle= en-abstract= kn-abstract=Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials. en-copyright= kn-copyright= en-aut-name=AkahoshiYu en-aut-sei=Akahoshi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InamotoYoshihiro en-aut-sei=Inamoto en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SpyrouNikolaos en-aut-sei=Spyrou en-aut-mei=Nikolaos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakasoneHideki en-aut-sei=Nakasone en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DinizMarcio A. en-aut-sei=Diniz en-aut-mei=Marcio A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AyukFrancis en-aut-sei=Ayuk en-aut-mei=Francis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChoeHannah K. en-aut-sei=Choe en-aut-mei=Hannah K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EtoTetsuya en-aut-sei=Eto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EtraAaron M. en-aut-sei=Etra en-aut-mei=Aaron M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HexnerElizabeth O. en-aut-sei=Hexner en-aut-mei=Elizabeth O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HiramotoNobuhiro en-aut-sei=Hiramoto en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HoganWilliam J. en-aut-sei=Hogan en-aut-mei=William J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HollerErnst en-aut-sei=Holler en-aut-mei=Ernst kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KataokaKeisuke en-aut-sei=Kataoka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawakitaToshiro en-aut-sei=Kawakita en-aut-mei=Toshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TanakaTakashi en-aut-sei=Tanaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=UchidaNaoyuki en-aut-sei=Uchida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=VasovaIngrid en-aut-sei=Vasova en-aut-mei=Ingrid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YoshiharaSatoshi en-aut-sei=Yoshihara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=IshimaruFumihiko en-aut-sei=Ishimaru en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ChenYi-Bin en-aut-sei=Chen en-aut-mei=Yi-Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamuraRyotaro en-aut-sei=Nakamura en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=FerraraJames L. M. en-aut-sei=Ferrara en-aut-mei=James L. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=LevineJohn E. en-aut-sei=Levine en-aut-mei=John E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TeshimaTakanori en-aut-sei=Teshima en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=2 en-affil=Department of Blood and Marrow Transplantation and Cellular Therapy, Fujita Health University School of Medicine kn-affil= affil-num=3 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=4 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=5 en-affil=Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf kn-affil= affil-num=8 en-affil=Division of Hematology, Blood and Marrow Transplantation Program, The Ohio State University Comprehensive Cancer Center kn-affil= affil-num=9 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Hamanomachi Hospital kn-affil= affil-num=11 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=12 en-affil=Department of Medicine and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Department of Hematology, Kobe City Medical Center General Hospital kn-affil= affil-num=14 en-affil=Division of Hematology, Mayo Clinic kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Internal Medicine III, University of Regensburg kn-affil= affil-num=16 en-affil=Division of Molecular Oncology, National Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Department of Hematology, National Hospital Organization Kumamoto Medical Center kn-affil= affil-num=18 en-affil=Department of Hematology, Kanagawa Cancer Center kn-affil= affil-num=19 en-affil=Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital kn-affil= affil-num=21 en-affil=Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universit?t Erlangen-N?rnberg and University Hospital Erlangen kn-affil= affil-num=22 en-affil=Department of Hematology, Hyogo Medical University Hospital kn-affil= affil-num=23 en-affil=Technical Department, Japanese Red Cross Blood Service Headquarters kn-affil= affil-num=24 en-affil=Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=25 en-affil=Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital kn-affil= affil-num=26 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=27 en-affil=Department of Hematology and Hematopoietic Cell Transplantation, City of Hope kn-affil= affil-num=28 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=29 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=30 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=31 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=32 en-affil=Department of Hematology, Hokkaido University Faculty of Medicine and Graduate School of Medicine 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=2025 dt-pub=20250908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of ciclosporin monotherapy in non-severe aplastic anaemia not requiring transfusions: Results from a multicentre phase II study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The efficacy of ciclosporin (CsA) to treat transfusion-independent non-severe aplastic anaemia (TI-NSAA) has not yet been systematically evaluated. We conducted a prospective trial in patients with TI-NSAA treated with CsA monotherapy. CsA (3.5?mg/kg/day) was administered to patients with TI-NSAA aged ?16. The CsA dose was adjusted to maintain a blood CsA level of ?600?ng/mL at 2?h post-administration. Blood cell counts were assessed after 8, 16 and 52?weeks of therapy. Thirty-two evaluable patients from 21 institutions were enrolled. The median age was 63.5 (range: 16?83) years. At 8?weeks, haematological improvement, with increases in haemoglobin (Hb) ?1.5?g/dL (haematological improvement in erythrocytes [HI-E]) and platelet count ?30?~?109/L (haematological improvement in platelets [HI-P]), was observed in 0/25 (0%) and 6/32 (19%) evaluable cases respectively. HI-E and HI-P occurred in 1/25 (4%) and 10/32 (31%) patients at 16?weeks, respectively, and at 52?weeks in 5/25 (20%) and 16/32 (50%) patients respectively. Nine grade 3 adverse events (AEs) occurred in six patients, but there were no grade ?4 AEs. Ten of the 32 patients experienced grade 2 renal toxicity. Low-dose CsA is effective in TI-NSAA patients and demonstrates minimal renal toxicity. However, at least 16?weeks are necessary to adequately evaluate its efficacy. en-copyright= kn-copyright= en-aut-name=IshiyamaKen en-aut-sei=Ishiyama en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamazakiMasahide en-aut-sei=Yamazaki en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaruyamaHiroyuki en-aut-sei=Maruyama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosonoNaoko en-aut-sei=Hosono en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamaguchiHiroki en-aut-sei=Yamaguchi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanimotoKazuki en-aut-sei=Tanimoto en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiuraHiroyuki en-aut-sei=Sugiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UsukiKensuke en-aut-sei=Usuki en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshimuraKenichi en-aut-sei=Yoshimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OgawaSeishi en-aut-sei=Ogawa en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KanakuraYuzuru en-aut-sei=Kanakura en-aut-mei=Yuzuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsumuraItaru en-aut-sei=Matsumura en-aut-mei=Itaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AkashiKoichi en-aut-sei=Akashi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakaoShinji en-aut-sei=Nakao en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Kanazawa University Hospital kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Keiju Medical Center kn-affil= affil-num=3 en-affil=Department of Hematology, Kanazawa University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, University of Fukui Hospital kn-affil= affil-num=5 en-affil=Department of Hematology, Nippon Medical School kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Japanese Red Cross Fukuoka Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers kn-affil= affil-num=9 en-affil=Department of Hematology, NTT Medical Center Tokyo kn-affil= affil-num=10 en-affil=Department of Biostatistics and Health Data Science, Graduate School of Medical Science, Nagoya City University kn-affil= affil-num=11 en-affil=Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University kn-affil= affil-num=12 en-affil=Sumitomo Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology, Kanazawa University Hospital kn-affil= en-keyword=ciclosporin kn-keyword=ciclosporin en-keyword=prospective study kn-keyword=prospective study en-keyword=renal toxicity kn-keyword=renal toxicity en-keyword=transfusion-independent non-severe aplastic anaemia kn-keyword=transfusion-independent non-severe aplastic anaemia END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=6 article-no= start-page=e098532 end-page= 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=Protocol for a multicentre, open-label, dose-escalation phase I/II study evaluating the tolerability, safety, efficacy and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with aggressive natural killer cell leukaemia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Aggressive natural killer cell leukaemia (ANKL) is a rare form of NK cell lymphoma with a very low incidence and poor prognosis. While multi-agent chemotherapy including L-asparaginase has been used to treat ANKL patients, they often cannot receive adequate chemotherapy at diagnosis due to liver dysfunction. PPMX-T003, a fully human monoclonal antibody targeting the transferrin receptor 1, shows promise in treating ANKL by helping patients recover from fulminant clinical conditions, potentially enabling a transition to chemotherapy. This study aimed to evaluate the tolerability, safety, efficacy, and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with ANKL.
Methods and analysis This multicentre, open-label, dose-escalation phase I/II study will be conducted at nine hospitals in Japan. Patients diagnosed with ANKL (whether as a primary or recurrent disease) and exhibiting abnormal liver function or hepatomegaly due to the primary disease will be included. The primary endpoint is the tolerability and safety of repeated continuous intravenous administration of PPMX-T003 in the first course, based on adverse events and dose-limiting toxicities. PPMX-T003 will be administered as a continuous intravenous infusion every 24?hours for five consecutive days, followed by a 2-day break. Pretreatment will be provided to minimise the risk of infusion-related reactions. Initial doses of PPMX-T003 will be 0.5, 1.0 or 2.0 mg/kg, with subsequent dose increases determined by the Data and Safety Monitoring Committee. The sample size is set at seven participants, with enrolment increased to up to 12 participants if dose-limiting toxicities occur, based on feasibility due to the rarity of ANKL. Descriptive statistics will summarise data according to initial dose, and pharmacokinetic analysis will be conducted based on administered dose.
Ethics and dissemination This study was approved by the institutional review boards at participating hospitals. The results will be disseminated in peer-reviewed journals.
Trial registration number jRCT2061230008 (jRCT); NCT05863234 (ClinicalTrials.gov). en-copyright= kn-copyright= en-aut-name=FukuharaNoriko en-aut-sei=Fukuhara en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnizukaMakoto en-aut-sei=Onizuka en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=AndoKiyoshi en-aut-sei=Ando en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Hematology, Tohoku University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Tokai University School of Medicine Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=6 en-affil=Department of Hematology, Hiroshima University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=98 cd-vols= no-issue= article-no= start-page=103224 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=The vicious cycle between nutrient deficiencies and antibiotic-induced nutrient depletion at the host cell-pathogen interface: Coenzyme Q10 and omega-6 as key molecular players en-subtitle= kn-subtitle= en-abstract= kn-abstract=The increasing prevalence of antibiotic resistance and pathological inflammation underscores the importance of understanding the underlying biochemical and immune processes that govern the host-pathogen interface. Nutrient deficiency, compounded by antibiotic-induced nutrient depletion, forms a vicious cycle of overt inflammation, contributing to bacterial toxin translocation in human inter-organ and intra-organs milieus. Coenzyme Q10 (CoQ10) and omega-6 linoleic acid (LA 18:26) are integral to cellular membrane integrity and immune defense. However, the complex enzymatic steps at the host cell-pathogen interface remain poorly understood. This study is particularly timely, as it explores these knowledge gaps, which can inform the development of nutritional and therapeutic strategies that modulate or target these mechanisms. Using an infectious-inflamed cell co-culture model of the gut-liver axis, we exposed triple cell co-cultures of human intestinal epithelial cells (T84), macrophage-like THP-1 cells, and hepatic cells (Huh7) to linoleic acid-producing Lactobacillus casei (L. casei) and Pseudomonas aeruginosa strain PAO1 (PAO1). The cultures were incubated for 6?h in medium with or without ceftazidime antibiotic. PAO1 and L. casei exerted opposing effects on the secretion of Th1 cytokines IL-1, IL-6, and the Th 2-type cytokine IL-10. Inoculation with PAO1 decreased CoQ10 and linoleic acid levels compared to uninfected controls. L. casei restored cellular health and biofunctionality impaired by PAO1, indicating its benefit to the host's well-being. The antibiotic ceftazidime exerted dual effects, alleviating PAO1 toxicity while marginally disrupting the beneficial effects of L. casei. Our results show how the vicious cycle of nutrient deficiency and antibiotic-induced nutrient loss reinforces pathological inflammation at the host cell-pathogen interface and highlights the need for more appropriate targeted antibiotic use that preserves essential nutrients like CoQ10 and omega-6 fatty acids. Inflammatory responses driven by opportunistic pathogens and LA-producing bacteria represent opposing immunometabolic pathways that may provide insights into novel approaches for treating infection and reducing antibiotic resistance. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Bl?merSophia en-aut-sei=Bl?mer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=?ahi?n KayaAysel en-aut-sei=?ahi?n Kaya en-aut-mei=Aysel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Kr?gerSandra en-aut-sei=Kr?ger en-aut-mei=Sandra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=R?ckenChristoph en-aut-sei=R?cken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Sch?ferHeiner en-aut-sei=Sch?fer en-aut-mei=Heiner kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BockelmannWilhelm en-aut-sei=Bockelmann en-aut-mei=Wilhelm kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= affil-num=2 en-affil=Faculty of Medicine, Christian-Albrechts-University of Kiel kn-affil= affil-num=3 en-affil=Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University kn-affil= affil-num=4 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=5 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=6 en-affil=Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel kn-affil= affil-num=7 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=9 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= en-keyword=Antibiotics kn-keyword=Antibiotics en-keyword=Coenzyme Q10 kn-keyword=Coenzyme Q10 en-keyword=Infection kn-keyword=Infection en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Micronutrients kn-keyword=Micronutrients en-keyword=Oxidative stress kn-keyword=Oxidative stress 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=20251110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Approximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome. en-copyright= kn-copyright= en-aut-name=TanakayaKohji en-aut-sei=Tanakaya en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaguchiTatsuro en-aut-sei=Yamaguchi en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirataKeiji en-aut-sei=Hirata en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaMasayoshi en-aut-sei=Yamada en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KumamotoKensuke en-aut-sei=Kumamoto en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkiyamaYasuki en-aut-sei=Akiyama en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshimaruKei en-aut-sei=Ishimaru en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKoichi en-aut-sei=Okamoto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawasakiYuko en-aut-sei=Kawasaki en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KomineKeigo en-aut-sei=Komine en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakamotoAkira en-aut-sei=Sakamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=ShibataYoshiko en-aut-sei=Shibata en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShimamotoYusaku en-aut-sei=Shimamoto en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShimodairaHideki en-aut-sei=Shimodaira en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SekineShigeki en-aut-sei=Sekine en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakaoAkinari en-aut-sei=Takao en-aut-mei=Akinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakaoMisato en-aut-sei=Takao en-aut-mei=Misato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TakamizawaYasuyuki en-aut-sei=Takamizawa en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakeuchiYoji en-aut-sei=Takeuchi en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TanabeNoriko en-aut-sei=Tanabe en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ChinoAkiko en-aut-sei=Chino en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=ChoHourin en-aut-sei=Cho en-aut-mei=Hourin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=DoiSatoru en-aut-sei=Doi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=NakajimaTakeshi en-aut-sei=Nakajima en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamoriSakiko en-aut-sei=Nakamori en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakayamaYoshiko en-aut-sei=Nakayama en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NagasakiToshiya en-aut-sei=Nagasaki en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HasumiHisashi en-aut-sei=Hasumi en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=BannoKouji en-aut-sei=Banno en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=HinoiTakao en-aut-sei=Hinoi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=FujiyoshiKenji en-aut-sei=Fujiyoshi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HorimatsuTakahiro en-aut-sei=Horimatsu en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=MasudaKenta en-aut-sei=Masuda en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=MiguchiMasashi en-aut-sei=Miguchi en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=MizuuchiYusuke en-aut-sei=Mizuuchi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=MiyakuraYasuyuki en-aut-sei=Miyakura en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=MutohMichihiro en-aut-sei=Mutoh en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=YoshiokaTakahiro en-aut-sei=Yoshioka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=TanakaShinji en-aut-sei=Tanaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=SakamotoKazuhiro en-aut-sei=Sakamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SakamakiKentaro en-aut-sei=Sakamaki en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=ItabashiMichio en-aut-sei=Itabashi en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=IshidaHideyuki en-aut-sei=Ishida en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=TomitaNaohiro en-aut-sei=Tomita en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=SugiharaKenichi en-aut-sei=Sugihara en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=AjiokaYoichi en-aut-sei=Ajioka en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= affil-num=1 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=2 en-affil=Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=3 en-affil=Department of Surgery 1, University of Occupational and Environmental Health kn-affil= affil-num=4 en-affil=Endoscopy Division, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Genome Medical Science and Medical Genetics, Faculty of Medicine, Kagawa University kn-affil= affil-num=6 en-affil=Department of Surgery 1, University of Occupational and Environmental Health kn-affil= affil-num=7 en-affil=Division of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime University kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science kn-affil= affil-num=9 en-affil=College of Nursing, University of Hyogo kn-affil= affil-num=10 en-affil=Department of Medical Oncology, Tohoku University Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital 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=Himawari-No-Kai (Sunflower Association), a Patient Advocacy Group for Individuals and Families Affected By Lynch Syndrome kn-affil= affil-num=14 en-affil=Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Division of Medical Oncology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University kn-affil= affil-num=16 en-affil=Department of Pathology, Keio University School of Medicine kn-affil= affil-num=17 en-affil=Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=18 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=19 en-affil=Department of Colorectal Surgery, National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=22 en-affil=Department of Surgery, Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=23 en-affil=Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research kn-affil= affil-num=24 en-affil=Endoscopy Center, Tokyo Medical University Hospital kn-affil= affil-num=25 en-affil=Harmony Line (Association for Patients and Families With Familial Adenomatous Polyposis) kn-affil= affil-num=26 en-affil=Division of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer Institute kn-affil= affil-num=27 en-affil=Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=28 en-affil=Department of Pediatrics, Shinshu University School of Medicine kn-affil= affil-num=29 en-affil=Department of Gastroenterological Surgery, Saitama Cancer Center kn-affil= affil-num=30 en-affil=Department of Urology, Yokohama City University kn-affil= affil-num=31 en-affil=Center of Maternal -Fetal/Neonatal Medicine, Hiroshima University Hospital kn-affil= affil-num=32 en-affil=Department of Clinical and Molecular Genetics, Hiroshima University Hospital kn-affil= affil-num=33 en-affil=Department of Surgery, Kurume University School of Medicine kn-affil= affil-num=34 en-affil=Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital kn-affil= affil-num=35 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=36 en-affil=Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital kn-affil= affil-num=37 en-affil=Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=38 en-affil=Department of Colon and Pelvic Surgery, Cancer Prevention and Genetic Counseling, Tochigi Cancer Center kn-affil= affil-num=39 en-affil=Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=40 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=41 en-affil=JA Onomichi General Hospital kn-affil= affil-num=42 en-affil=Koshigaya Municipal Hospital kn-affil= affil-num=43 en-affil=Faculty of Health Data Science, Juntendo University kn-affil= affil-num=44 en-affil=Saiseikai Kazo Hospital kn-affil= affil-num=45 en-affil=Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=46 en-affil=Division of Cancer Treatment , Toyonaka Municipal Hospital kn-affil= affil-num=47 en-affil=Institute of Science Tokyo kn-affil= affil-num=48 en-affil=Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=Hereditary colorectal cancer kn-keyword=Hereditary colorectal cancer en-keyword=Guidelines kn-keyword=Guidelines en-keyword=Familial adenomatous polyposis kn-keyword=Familial adenomatous polyposis en-keyword=Lynch syndrome kn-keyword=Lynch syndrome END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=6 article-no= start-page=1297 end-page=1301 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gallbladder edema as a clue to zolbetuximab-associated protein-losing enteropathy in gastric cancer: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a rare case of protein-losing enteropathy (PLE) during zolbetuximab treatment in a 73-year-old woman with Stage IVB gastric cancer. After chemo-immunotherapy and curative surgery, 3rd-line treatment with capecitabine, oxaliplatin, and zolbetuximab was initiated due to recurrence. The patient developed persistent right upper abdominal pain; imaging revealed gallbladder wall edema, followed by mild gastric wall edema, despite unremarkable laboratory findings. Protein-losing scintigraphy demonstrated abnormal gastric protein leakage, leading to a diagnosis of PLE. While gastrointestinal toxicity is known with zolbetuximab, this is, to our knowledge, the first clinically diagnosed case of PLE in which gallbladder edema served as a diagnostic clue. As treatment strategies for advanced gastric cancer grow increasingly complex, achieving maximum therapeutic benefit requires not only optimal drug selection but also timely recognition and management of adverse events. With the broader use of zolbetuximab, clinicians should be mindful of this rare but potentially significant complication. en-copyright= kn-copyright= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko 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=HanzawaShunya en-aut-sei=Hanzawa en-aut-mei=Shunya 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=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=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=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=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, 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 Gastroenterology and Hepatology, 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= en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=Zolbetuximab kn-keyword=Zolbetuximab en-keyword=CLDN 18.2 kn-keyword=CLDN 18.2 en-keyword=Protein-losing enteropathy kn-keyword=Protein-losing enteropathy en-keyword=Gallbladder edema kn-keyword=Gallbladder edema END start-ver=1.4 cd-journal=joma no-vol=81 cd-vols= no-issue= article-no= start-page=152587 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The diagnostic utility and frequency of CD56 expression in plasma cell myeloma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plasma cell myeloma (PCM) is a hematological malignancy characterized by systemic proliferation of neoplastic plasma cells within the bone marrow. Diagnosis requires clinical findings and immunohistochemical staining, including CD138, CD79a, cyclin D1, immunoglobulin (Ig), and (Ig). However, CD79a and cyclin D1 have limited sensitivity and specificity, and Ig/Ig assessment is often difficult due to overstaining. Therefore, more reliable antibodies are needed to accurately diagnose PCM. In this study, we examined the diagnostic utility of CD56 expression in PCM. We retrospectively performed immunostaining for CD138, CD56, CD79a, cyclin D1, Ig, and Ig in bone marrow samples from 116 patients with PCM.
CD56 expression was observed in 85/116 cases (73.3 %), CD79a was downregulated in 46/116 cases (39.7 %), and cyclin D1 expression was observed in 42/116 cases (36.2 %). The expression of CD56 was significantly higher than that of CD79a and cyclin D1 (both p < 0.001). The combination of two antibodies resulted in the highest detection rate when combining CD56 and CD79a (105/116, 90.5 %), which was significantly higher than the detection rates of CD56 and cyclin D1 (93/116, 80.2 %) and CD79a and cyclin D1 (75/116, 64.7 %) (both p < 0.001). In contrast, lymphoplasmacytic lymphoma and marginal zone lymphoma lacked CD56 and cyclin D1 expression. Furthermore, in cases where light chain restriction was undetectable (11/116, 9.5 %), all could be diagnosed as PCM based on CD56, CD79a, and cyclin D1. Among these, CD56 showed the highest detection rate (8/11, 72.7 %).
These findings highlight CD56 as a helpful marker for PCM diagnosis and support further clinical research.
en-copyright= kn-copyright= en-aut-name=ImaiMidori en-aut-sei=Imai en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaratakeTomoka en-aut-sei=Haratake en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaRio en-aut-sei=Yamada en-aut-mei=Rio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoSyoma en-aut-sei=Kato en-aut-mei=Syoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TabeMizuha en-aut-sei=Tabe en-aut-mei=Mizuha 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=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Diagnostic Pathology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=Plasma cell myeloma kn-keyword=Plasma cell myeloma en-keyword=Immunohistochemical staining kn-keyword=Immunohistochemical staining en-keyword=CD56 kn-keyword=CD56 END start-ver=1.4 cd-journal=joma no-vol=152 cd-vols= no-issue=22 article-no= start-page=dev204763 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ROS produced by Dual oxidase regulate cell proliferation and haemocyte migration during leg regeneration in the cricket en-subtitle= kn-subtitle= en-abstract= kn-abstract=Many animals regenerate lost body parts through several signalling pathways; however, the triggers that initiate regeneration remain unclear. In the present study, we focused on the role of reactive oxygen species (ROS) produced by the NADPH oxidase Dual oxidase (Duox) during cricket leg regeneration. The results showed that ROS levels were upregulated during leg regeneration and decreased by DuoxRNAi. In DuoxRNAi nymphs, wound closure and scab formation were incomplete 2?days after amputation, and hypertrophy occurred in the distal region of the regenerating legs at 5?days after amputation. In addition, the hypertrophic phenotype was induced by DuoxARNAi and NADPH oxidase inhibitor treatment. During hypertrophy, haemocytes, including plasmatocytes, oenocytoids and granulocytes, accumulated. Proliferation of haemocytes in regenerating legs was not increased by DuoxRNAi; however, haemocyte accumulation was regulated by the Spatzle (Spz) family molecules, which are Toll receptor ligands. As the exoskeleton of DuoxRNAi nymphs was thinner than that of the control, excessive haemocyte accumulation can cause hypertrophy in DuoxRNAi nymphs. Thus, Duox-derived ROS are involved in wound healing and haemocyte accumulation through the Spz/Toll signalling pathway during leg regeneration in crickets. en-copyright= kn-copyright= en-aut-name=Okumura-HironoMisa en-aut-sei=Okumura-Hirono en-aut-mei=Misa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BandoTetsuya en-aut-sei=Bando en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaYoshimasa en-aut-sei=Hamada en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Regeneration kn-keyword=Regeneration en-keyword=Reactive oxygen species (ROS) kn-keyword=Reactive oxygen species (ROS) en-keyword=NADPH oxidase (Nox) kn-keyword=NADPH oxidase (Nox) en-keyword=Dual oxidase (Duox) kn-keyword=Dual oxidase (Duox) en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Gryllus bimaculatus kn-keyword=Gryllus bimaculatus 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=20251124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of the small-field output factor in eclipse modeling methods using representative beam and measured data with averaged ionization chamber and diode detector measurements en-subtitle= kn-subtitle= en-abstract= kn-abstract=Beam modeling for radiotherapy treatment planning systems (RTPS) can be performed using representative beam data (RBD) or direct measurements. However, RBD typically excludes output factor (OPF) measurements for fields smaller than 3 ~ 3 cm2. The Eclipse treatment planning system addresses this limitation by incorporating measured OPF data for fields as small as 1 ~ 1 cm2. Although existing studies have primarily examined the accuracy of small-field OPFs for plastic scintillator detectors, studies directly comparing the OPF values obtained through RBD modeling with and without OPF measurements for small field sizes are limited. Therefore, this study proposes a novel measurement approach using data averaged from an ion chamber and diode detector for small-field dosimetry to provide critical insights into the integration of OPFs for these small field sizes in RBD-based beam modeling. We systematically evaluated the impact of small-field OPF measurements on beam modeling accuracy by comparing three distinct approaches: (1) RBD-based modeling without small-field OPF data, (2) RBD-based modeling incorporating measured small-field OPF data, and (3) modeling based solely on measured data, with and without the inclusion of 1 ~ 1 cm2 field sizes. In addition, we compared OPF values obtained from a W2 plastic scintillator detector with the averaged OPF values from a PinPoint 3D ion chamber and EDGE diode detector across multiple beam energies and flattening filter-free (FFF) configurations. Our analysis included field sizes ranging from 1 ~ 1 cm2 to 40 ~ 40 cm2. The results demonstrated that for square fields, OPF calculation differences between RBD modeling with and without measured data were < 1.5%, < 4.5%, and < 4.5% at 1 ~ 1 cm2, and < 0.5%, < 1.5%, and < 1.5% at 2? ~ ?2 cm2, respectively. The RBD group exhibited a trend in which the OPF difference increased with the expansion of the irradiation field size. Notably, the most significant variations between modeling approaches occurred along the upper jaw expansion direction in rectangular fields. This suggests that a thorough evaluation is necessary for modeling results with an OPF??? 1 ~ 1 cm2. This study highlights the advantages and disadvantages of beam modeling using measured OPF and RBD, providing valuable insights for future facilities that rely solely on RBD for beam modeling. en-copyright= kn-copyright= en-aut-name=NishiokaKunio en-aut-sei=Nishioka en-aut-mei=Kunio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuniiYuki en-aut-sei=Kunii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=SakamotoYuichi en-aut-sei=Sakamoto en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamotoAkira en-aut-sei=Nakamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiShotaro en-aut-sei=Takahashi en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Radiology, Tokuyama Central Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Tokuyama Central Hospital kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Radiology, Tokuyama Central Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Tokuyama Central Hospital kn-affil= affil-num=6 en-affil=Department of Radiology, Tokuyama Central Hospital kn-affil= en-keyword=Beam modeling kn-keyword=Beam modeling en-keyword=Plastic scintillator detector kn-keyword=Plastic scintillator detector 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=26 cd-vols= no-issue=11 article-no= start-page=e70168 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative Genomic Analysis Identifies FleQ and GcbB as Virulence-Associated Factors in Pseudomonas syringae pv. tabaci Strains en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pseudomonas syringae pv. tabaci (Pta) is an important plant pathogen, which causes wildfire disease in Nicotiana species. However, the genetic basis underlying strain-level differences in virulence remains largely unresolved. To address this, we performed a comparative genomic analysis between a highly virulent strain Pta6605 and a less virulent strain Pta7375. Despite high overall genome similarity, we identified key single-nucleotide polymorphisms, including premature stop-codon mutations in seven open reading frames in Pta7375. Notably, point mutations in two regulatory genes, such as fleQ, which encodes a transcription factor essential for flagellar biogenesis and biofilm formation, and gcbB, which encodes a GGDEF domain-containing diguanylate cyclase responsible for cyclic dimeric guanosine monophosphate (c-di-GMP) synthesis, were implicated in virulence disparity. Functional analyses using deletion and locus replacement mutants in the Pta6605 background revealed that the disruption of fleQ markedly reduced motility, flagellin production, c-di-GMP accumulation, biofilm formation and virulence level mirroring the Pta7375 phenotype. The gcbB replacement mutant showed reduced disease symptom development, although c-di-GMP levels remained comparable to the Pta6605 wild type. Locus replacement between strains confirmed that a point mutation in fleQ was the primary driver of reduced motility and flagellin expression in Pta7375. These findings indicate that the reduced virulence of Pta7375 is associated with impaired regulation of flagella-related genes and disruption of the FleQ-mediated c-di-GMP signalling, underscoring the value of comparative genomics in disentangling the complex regulatory networks that govern virulence in plant pathogens. en-copyright= kn-copyright= en-aut-name=HidayatMuhammad Taufiq en-aut-sei=Hidayat en-aut-mei=Muhammad Taufiq kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiokaKei en-aut-sei=Yoshioka en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimuraTakafumi en-aut-sei=Nishimura en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsaiShuta en-aut-sei=Asai en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasudaSachiko en-aut-sei=Masuda en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShirasuKen en-aut-sei=Shirasu en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=YamamotoMikihiro en-aut-sei=Yamamoto en-aut-mei=Mikihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Agriculture, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Center for Sustainable Resource Science, RIKEN-TRIP kn-affil= affil-num=6 en-affil=Center for Sustainable Resource Science, RIKEN-TRIP 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=comparative genomics kn-keyword=comparative genomics en-keyword=cyclic-di- GMP kn-keyword=cyclic-di- GMP en-keyword=fleQ kn-keyword=fleQ en-keyword=gcbB kn-keyword=gcbB en-keyword=Pseudomonas syringae kn-keyword=Pseudomonas syringae 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=20251119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Role of the Mylohyoid Line in the Spread of Mandibular Odontogenic Deep Neck Infection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Although mandibular odontogenic deep neck infections are occasionally fatal, the transmission pathway has not been elucidated.
Materials and Methods: This multicenter retrospective study was comprised of the patients of both sexes who were over 18?years of age and who had mandibular odontogenic deep neck abscesses. The patients' characteristics, laboratory tests, and radiographic findings were analyzed.
Results: One hundred eighteen patients with mandibular odontogenic deep neck abscesses were included. Bone resorption superior to the mylohyoid line and the related abscess formation in submandibular space or submental space were both significantly associated with the presence of sublingual space abscess. In addition, the type of causative tooth was not a risk factor for abscess formation in both the sublingual space and gsubmandibular or submentalh space.
Conclusions: When an odontogenic lesion is located superior to the mylohyoid line, the abscess tends to initially form in the sublingual space and subsequently spread to the submandibular or submental space. Since any mandibular tooth can lead to abscess formation in these regions, oral and maxillofacial surgeons should carefully assess the anatomical position of the lesion and accurately identify the causative tooth. en-copyright= kn-copyright= en-aut-name=IwataEiji en-aut-sei=Iwata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikutaShogo en-aut-sei=Kikuta en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanekoNaoki en-aut-sei=Kaneko en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKotaro en-aut-sei=Sato en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitagawaNorio en-aut-sei=Kitagawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuoKatsuhisa en-aut-sei=Matsuo en-aut-mei=Katsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SameshimaJunsei en-aut-sei=Sameshima en-aut-mei=Junsei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TachibanaAkira en-aut-sei=Tachibana en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawanoShintaro en-aut-sei=Kawano en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KusukawaJingo en-aut-sei=Kusukawa en-aut-mei=Jingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AkashiMasaya en-aut-sei=Akashi en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=4 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Nagoya University, Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=9 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital kn-affil= affil-num=11 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=12 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=13 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= en-keyword=causative tooth kn-keyword=causative tooth en-keyword=mylohyoid line kn-keyword=mylohyoid line en-keyword=odontogenic deep neck abscesses kn-keyword=odontogenic deep neck abscesses en-keyword=odontogenic deep neck infections kn-keyword=odontogenic deep neck infections en-keyword=transmission pathway kn-keyword=transmission pathway 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=20251023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative Analysis of a Dual DNA?RNA Panel and a DNA-Only Panel for Sarcoma: Real-World Data From a Nationwide Genomic Database en-subtitle= kn-subtitle= en-abstract= kn-abstract=Next-generation sequencing-based comprehensive cancer genomic profiling is promising in cancer management; however, most studies rely on tumor-only DNA panels from single institutions. In 2023, Japan introduced an insurance-covered cancer genomic profiling test?the GenMine TOP Cancer Genome Profiling System?a dual DNA?RNA panel with matched tumor?normal testing. This study evaluated its utility compared to a conventional DNA-only test (FoundationOne CDx) in managing sarcoma patients using a nationwide genetic profiling database provided by the Center for Cancer Genomics and Advanced Therapeutics. This study included 1046 patients registered between August 2023 and October 2024. The dual DNA?RNA test identified significantly more fusion genes (20.3% vs. 7.4%, p? Material and Methods: This retrospective study included 17 patients with 17 renal cell carcinomas who underwent transarterial ethiodized-oil marking before cryoablation. Tumor feeders were automatically detected on transarterial renal computed tomography angiography images using the automated feeder-detection software with three virtual-target definitions: small (ellipsoidal area maximized within the tumor contour), medium (ellipsoidal area covering the entire tumor with a minimal peripheral margin), and large (ellipsoidal area including the tumor and a 5-mm peripheral margin). The detected feeders were classified as true or false positives according to the findings of selective renal arteriography, by consensus of two interventional radiologists. Feeder-detection sensitivity and the mean number of false-positive feeders per tumor were calculated for each virtual-target definition.
Results: For 17 tumors, 25 feeding arteries were identified on the arteriography. The feeder-detection sensitivity of the software was 80.0% (20/25), 88.0% (22/25), and 48.0% (12/25) for small, medium, and large virtual targets, respectively. The mean } standard deviation number of false-positive feeders per tumor was 0.82 } 1.3, 1.41 } 1.1, and 2.82 } 1.6 when using small, medium, and large virtual-target definitions, respectively.
Conclusions: The detection rate of renal cell carcinoma feeders with the automated feeder-detection software varies according to the virtual-target definition. Using a medium virtual target, covering the entire tumor with a minimal peripheral margin, may provide the highest sensitivity and an acceptable number of false-positive feeders. en-copyright= kn-copyright= en-aut-name=OkamotoSoichiro en-aut-sei=Okamoto en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawabataTakahiro en-aut-sei=Kawabata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MunetomoKazuaki en-aut-sei=Munetomo en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UmakoshiNoriyuki en-aut-sei=Umakoshi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigakiFumiyo en-aut-sei=Higaki en-aut-mei=Fumiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiology, Tsuyama Chuo Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=5 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiology, Medical Development Field, Okayama University kn-affil= affil-num=8 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=computed tomography angiography kn-keyword=computed tomography angiography en-keyword=kidney kn-keyword=kidney en-keyword=software kn-keyword=software en-keyword=therapeutic embolization kn-keyword=therapeutic embolization END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=1 article-no= start-page=95 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=A case of a large venous ring around the mandibular condyle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anatomical details regarding venous drainage of the head and neck are an important matter for surgeons to avoid unnecessary complications such as hemorrhage. This report describes a case of the large venous ring around the mandibular condyle found in the cadaver. The left maxillofacial region of a latex-injected embalmed male cadaver (82 years of age at death) was dissected. The large two maxillary veins ran lateral to the capsule and superior to the mandibular notch and coursed posteroinferiorly to merge, and one trunk was formed at the posterior border of the ramus. It then received the superficial temporal vein superiorly to form the retromandibular vein (RMV). In addition, three maxillary veins were drained from the pterygoid venous plexus (PVP), medial to the ramus, one maxillary vein drained from the PVP into the RMV trunk, while two maxillary veins drained from the PVP into the anterior division of the RMV. All five large veins lateral and medial to the condyle drained from the PVP into the RMV. The knowledge of such an anatomical variation might prevent intraoperative bleeding in the temporomandibular joint region. en-copyright= kn-copyright= en-aut-name=NishiKeitaro en-aut-sei=Nishi en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkuiTatsuo en-aut-sei=Okui en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KusukawaJingo en-aut-sei=Kusukawa en-aut-mei=Jingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TubbsR. Shane en-aut-sei=Tubbs en-aut-mei=R. Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=2 en-affil=Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=5 en-affil=Department of Neurosurgery, Clinical Neuroscience Research Center, Tulane University School of Medicine kn-affil= affil-num=6 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= en-keyword=Maxillary vein kn-keyword=Maxillary vein en-keyword=Temporomandibular joint kn-keyword=Temporomandibular joint en-keyword=Cadaver kn-keyword=Cadaver en-keyword=Anatomy kn-keyword=Anatomy 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=20250917 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of CT-assessed sarcopenia on the severity of odontogenic deep neck infections: a retrospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sarcopenia is increasingly recognized as a key predictor of adverse health outcomes. This study aimed to evaluate the impact of computed tomography-assessed sarcopenia (CT?SP) on the clinical severity and hospitalization duration of odontogenic deep neck infections (DNIs). Total of 119 patients admitted for odontogenic DNI treatment were included. Patients were divided into two groups by DNI clinical severity (severe or mild) and the patients' characteristics, including CT?SP based on skeletal muscle index (SMI), were compared between two groups. Multivariable logistic regression analysis was performed to identify independent risk factors for severe DNI. The correlation between SMI and hospitalization duration was assessed using Spearmanfs rank correlation coefficient. Of the 119 patients, 60 (50.4%) presented with severe DNIs, including deep neck abscesses and necrotizing soft tissue infections. After adjusting for potential confounders, multivariable analysis identified CT?SP as the sole independent risk factor associated with severe DNI (Odds Ratio?=?3.04; 95% Confidence Interval, 1.20?7.71; p?=?0.019). Furthermore, SMI demonstrated a significant, weak negative correlation with the hospitalization duration (r?=?? 0.331, p? 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 11-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 11-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=11-HSD1 kn-keyword=11-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 1 receptors can lead to organ protection through anti?inflammatory and anti?apoptotic effects. Additionally, although the 1 receptor pathway is blocked by the 1 blocker, the 2 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 1 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? (TNF?) 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 AMPK (pAMPK) 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? and iNOS mRNA levels, TUNEL?positive cells and cleaved caspase?3 expression. Furthermore, landiolol administration following HSR treatment increased pAMPK 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, pAMPK 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=1 blocker kn-keyword=1 blocker en-keyword=inflammation kn-keyword=inflammation en-keyword=apoptosis kn-keyword=apoptosis 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? 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=25 cd-vols= no-issue= article-no= start-page=101057 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=Mid-term (30- to 90-day) neurological changes in out-of-hospital cardiac arrest survivors receiving extracorporeal cardiopulmonary resuscitation: a nationwide retrospective study (the JAAM-OHCA registry) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Few studies have examined mid-term neurological changes in out-of-hospital cardiac arrest (OHCA) patients after receiving extracorporeal cardiopulmonary resuscitation (ECPR). This study aimed to evaluate neurological improvements between 30 and 90 days in OHCA patients treated with ECPR or conventional cardiopulmonary resuscitation (CCPR) using a large nationwide cohort.
Methods: This retrospective multicenter study used data from a Japanese nationwide OHCA registry. Participants were categorized into ECPR and CCPR groups based on the initial resuscitation method. Neurological changes between 30 and 90 days were assessed using Cerebral Performance Category (CPC) scores. The primary outcome was neurological improvement, defined as an improvement in CPC score during this period.
Results: A total of 4467 OHCA survivors at 30 days were included, 669 in the ECPR group and 3798 in the CCPR group. At 30 days, favorable neurological outcomes were observed in 318 ECPR patients (47.5 %) and 2103 CCPR patients (55.4 %). Neurological improvement between 30 and 90 days was more frequent in the ECPR group (83 [12.4 %] vs. 258 [6.7 %]). There was no significant difference in 90-day mortality between the two groups (82 [12.2 %] vs. 519 [13.6 %]). ECPR was independently associated with 30- to 90-day neurological improvement (adjusted odds ratio (OR) 2.01; 95 % confidence interval (CI), 1.38?2.93) but was not associated with 90-day mortality (adjusted OR 1.11; 95 % CI, 0.77?1.59).
Conclusion: ECPR was associated with a greater likelihood of neurological improvement between 30 and 90 days. By 90 days, mortality was nearly the same in both groups. en-copyright= kn-copyright= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UedaYoshiyuki en-aut-sei=Ueda en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 ORCID= affil-num=1 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=2 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=3 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=4 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=5 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=6 en-affil=Okayama University, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Epidemiology kn-affil= affil-num=7 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= affil-num=8 en-affil=Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine kn-affil= en-keyword=Post-cardiac arrest syndrome kn-keyword=Post-cardiac arrest syndrome en-keyword=Cardiac arrest kn-keyword=Cardiac arrest en-keyword=ECPR kn-keyword=ECPR en-keyword=Patient outcome assessment kn-keyword=Patient outcome assessment en-keyword=Prognostication kn-keyword=Prognostication en-keyword=Venoarterial ECMO kn-keyword=Venoarterial ECMO END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e06572 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Viral RNA Silencing Suppressor Modulates Reactive Oxygen Species Levels to Induce the Autophagic Degradation of Dicer]Like and Argonaute]Like Proteins en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mounting evidence indicates that viruses exploit elevated reactive oxygen species (ROS) levels to promote replication and pathogenesis, yet the mechanistic underpinnings of this viral strategy remain elusive for many viral systems. This study uncovers a sophisticated viral counter-defense mechanism in the Cryphonectria hypovirus 1 (CHV1)-Fusarium graminearum system, where the viral p29 protein subverts host redox homeostasis to overcome antiviral responses. That p29 directly interacts with and inhibits the enzymatic activity of fungal NAD(P)H-dependent FMN reductase 1 (FMR1), leading to increased ROS accumulation and subsequent autophagy activation is demonstrated. Strikingly, this ROS-induced autophagy selectively targets for degradation two core antiviral RNA silencing components against CHV1 in F. graminearum, Dicer-like 2 (DCL2) and Argonaute-like 1 (AGL1), thereby compromising the host's primary antiviral defense system. Genetic analysis confirms this coordinated hijacking of host machineries, as CHV1 shows enhanced accumulation in the FMR1 knockout and reduced accumulation in autophagy-deficient fungal strains. This work reveals a tripartite interplay among oxidative stress, autophagy, and RNA silencing that CHV1 manipulates through p29 multifunctional activity. These findings provide a model for how viruses coordinately regulate distinct host defense systems to optimize infection. en-copyright= kn-copyright= en-aut-name=ZhaiShiyu en-aut-sei=Zhai en-aut-mei=Shiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PangTianxing en-aut-sei=Pang en-aut-mei=Tianxing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PengShiyu en-aut-sei=Peng en-aut-mei=Shiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZouShenshen en-aut-sei=Zou en-aut-mei=Shenshen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DengZhiping en-aut-sei=Deng en-aut-mei=Zhiping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KangZhensheng en-aut-sei=Kang en-aut-mei=Zhensheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndikaIda Bagus en-aut-sei=Andika en-aut-mei=Ida Bagus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SunLiying en-aut-sei=Sun en-aut-mei=Liying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=2 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=3 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=4 en-affil=Department of Plant Pathology, College of Plant Protection, Shandong Agricultural University kn-affil= affil-num=5 en-affil=Institute of Virology and Biotechnology, Zhejiang Academy of Agricultural Sciences kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=7 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=8 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= affil-num=9 en-affil=State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University kn-affil= en-keyword=argonaute kn-keyword=argonaute en-keyword=autophagic degradation kn-keyword=autophagic degradation en-keyword=cryphonectria hypovirus 1 kn-keyword=cryphonectria hypovirus 1 en-keyword=dicer kn-keyword=dicer en-keyword=reactive oxygen species kn-keyword=reactive oxygen species en-keyword=RNA silencing suppressor kn-keyword=RNA silencing suppressor END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=234 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rotenone targets midbrain astrocytes to produce glial dysfunction-mediated dopaminergic neurodegeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Exposure to pesticides, such as rotenone or paraquat, is an environmental factor that plays an important role in the pathogenesis of Parkinson's disease (PD). Rotenone induces PD-like pathology and is therefore used to develop parkinsonian animal models. Dopaminergic neurotoxicity caused by rotenone has been attributed to the inhibition of mitochondrial complex I, oxidative stress and neuroinflammation; however, the mechanisms underlying selective dopaminergic neurodegeneration by rotenone remain unclear. To resolve this, we focused on glial diversity and examined whether the brain region-specific glial response to rotenone could determine the vulnerability of dopaminergic neurons using primary cultured neurons, astrocytes and microglia from the midbrain and striatum of rat embryos and rotenone-injected PD model mice. Direct neuronal treatment with low-dose rotenone failed to damage dopaminergic neurons. Conversely, rotenone exposure in the presence of midbrain astrocyte and microglia or conditioned media from rotenone-treated midbrain glial cultures containing astrocytes and microglia produced dopaminergic neurotoxicity, but striatal glia did not. Surprisingly, conditioned media from rotenone-treated midbrain astrocytes or microglia monocultures did not affect neuronal survival. We also demonstrated that rotenone targeted midbrain astrocytes prior to microglia to induce dopaminergic neurotoxicity. Rotenone-treated astrocytes produced secreted protein acidic and rich in cysteine (SPARC) extracellularly, which induced microglial proliferation, increase in IL-1 and TNF-, and NF-B (p65) nuclear translocation in microglia, resulting in dopaminergic neurodegeneration. In addition, rotenone exposure caused the secretion of NFAT-related inflammatory cytokines and a reduction in the level of an antioxidant metallothionein (MT)-1 from midbrain glia. Furthermore, we observed microglial proliferation and a decrease in the number of MT-positive astrocytes in the substantia nigra, but not the striatum, of low-dose rotenone-injected PD model mice. Our data highlight that rotenone targets midbrain astrocytes, leading to SPARC secretion, which promotes the neurotoxic conversion of microglia and leads to glial dysfunction-mediated dopaminergic neurodegeneration. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IsookaNami en-aut-sei=Isooka en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImafukuFuminori en-aut-sei=Imafuku en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomimotoKana en-aut-sei=Tomimoto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SogawaNorio en-aut-sei=Sogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology kn-affil= affil-num=9 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pharmacotherapy, School of Pharmacy, Shujitsu University kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Rotenone kn-keyword=Rotenone en-keyword=Astrocyte kn-keyword=Astrocyte en-keyword=Microglia kn-keyword=Microglia en-keyword=SPARC kn-keyword=SPARC en-keyword=Parkinson's disease kn-keyword=Parkinson's disease 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=20251102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PGN_0298 in the Assembly and Insertion Machinery (Aim) Operon Is Essential for the Viability of Porphyromonas gingivalis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Porphyromonas gingivalis is a typical periodontal pathogen, and one of its key virulence factors is the powerful protease gingipains. Gingipains are secreted via the type IX secretion system (T9SS) and are associated with the assembly and insertion machinery (Aim) operon (PGN_0296 to PGN_0301), which encodes both T9SS components and non-T9SS proteins. In this study, we investigated PGN_0298, a gene of unknown function within this operon, to elucidate its role in P. gingivalis and to gain insights into its potential function through bioinformatics analyses. Our results demonstrated that PGN_0298 is essential for the viability of P. gingivalis, despite having limited direct association with T9SS. Sequence homology and structure predictions indicate that PGN_0298 encodes a putative isoprenyl transferase. The essentiality of PGN_0298 underscores its potential as a novel drug target for the treatment of periodontal disease. en-copyright= kn-copyright= en-aut-name=OnoShintaro en-aut-sei=Ono en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WadaTakayuki en-aut-sei=Wada en-aut-mei=Takayuki 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= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Human Life and Ecology, Osaka Metropolitan University kn-affil= affil-num=7 en-affil=Department of Pathophysiology?Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=PGN_0298 kn-keyword=PGN_0298 en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=undecaprenyl pyrophosphate synthase kn-keyword=undecaprenyl pyrophosphate synthase END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=9916 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A node-localized efflux transporter for loading iron to developing tissues in rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Iron (Fe) is an essential micronutrient for plant growth and development. It plays crucial roles in various organs and tissues of plants, but the molecular mechanisms governing its distribution to the above-ground parts after root uptake remain unclear. In this study, we identify OsIET1 (Oryza sativa Iron Efflux Transporter 1), a rice gene highly expressed in the nodes. OsIET1 encodes a plasma membrane-localized protein, which shows efflux transport activity for ferrous iron. It is predominantly expressed in the xylem regions of diffuse vascular bundles, and its expression is upregulated under high Fe conditions. Disruption of OsIET1 impairs Fe allocation, reducing Fe transport to developing tissues (young leaves and grains), while increasing accumulation in nodes and older leaves. This misdistribution causes chlorosis in young leaves and decreases grain yield, especially under Fe-deficient conditions. Furthermore, we detect excessive Fe deposition around the xylem of diffuse vascular bundles in the nodes. Given the pivotal role of nodes in mineral distribution, our results indicate that OsIET1 mediates inter-vascular Fe transfer by facilitating Fe loading into the xylem of diffuse vascular bundles. This process ensures preferential Fe delivery to developing tissues, thereby promoting optimal plant growth and productivity. en-copyright= kn-copyright= en-aut-name=CheJing en-aut-sei=Che en-aut-mei=Jing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HuangSheng en-aut-sei=Huang en-aut-mei=Sheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=QuYuting en-aut-sei=Qu en-aut-mei=Yuting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiokaYuma en-aut-sei=Yoshioka en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomitaChiyuri en-aut-sei=Tomita en-aut-mei=Chiyuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=LiuZhenyang en-aut-sei=Liu en-aut-mei=Zhenyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShenRenfang en-aut-sei=Shen en-aut-mei=Renfang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng 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=State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences kn-affil= affil-num=8 en-affil=State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources, Okayama 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=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 gstealth effecth 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=12 cd-vols= no-issue= article-no= start-page=445 end-page=451 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=Endovascular Thrombectomy for Large Vessel Occlusion in a Patient on Venoarterial Extracorporeal Membrane Oxygenation: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Extracorporeal membrane oxygenation is utilized in the treatment of severe acute cardiac failure and respiratory failure. While it provides the advantage of oxygenating blood through extracorporeal circulation, it also carries risks of intracranial ischemic and hemorrhagic complications due to the continuous presence of artificial materials within the body. We encountered a case in which venoarterial extracorporeal membrane oxygenation was initiated for fulminant myocarditis, and the patient subsequently developed a large vessel occlusion. The diagnosis was confirmed using perfusion computed tomography. A visible thrombus was observed on the arterial cannula of the extracorporeal membrane oxygenation circuit, and the large vessel occlusion was determined to have been caused by thromboembolism. An immediate extracorporeal membrane oxygenation circuit exchange was performed, followed by endovascular thrombectomy. The patient experienced no perioperative complications and achieved a favorable neurological outcome. Endovascular thrombectomy in extracorporeal membrane oxygenation patients requires careful perioperative management and should be promptly performed in eligible cases of thromboembolic events. Furthermore, because patients on extracorporeal membrane oxygenation are often sedated and under intensive systemic management, regular neurological assessments and intracranial monitoring are essential for the early detection of intracranial pathologies. en-copyright= kn-copyright= en-aut-name=EBISUDANIYuki en-aut-sei=EBISUDANI en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=IWASAKIKeiichiro en-aut-sei=IWASAKI en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=KIMURARyu en-aut-sei=KIMURA en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KAWAKAMIMasato en-aut-sei=KAWAKAMI en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SOTOMEYuta en-aut-sei=SOTOME en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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= en-aut-name=TANAKAShota en-aut-sei=TANAKA en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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 Neurological Surgery, 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 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 Neurological Surgery, 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 Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=large vessel occlusion kn-keyword=large vessel occlusion en-keyword=endovascular thrombectomy kn-keyword=endovascular thrombectomy en-keyword=extracorporeal membrane oxygenation kn-keyword=extracorporeal membrane oxygenation en-keyword=mechanical circulatory support kn-keyword=mechanical circulatory support en-keyword=case report kn-keyword=case report END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=11 article-no= start-page=1677 end-page=1685 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250819 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of Cytoreductive Nephrectomy in the Immune Checkpoint Inhibitor Era: A Multicenter Collaborative Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: We aimed to evaluate overall survival (OS) and determine the optimal timing of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI)-based therapy.
Methods: This retrospective study reviewed medical records of 447 patients with mRCC treated with ICI at multiple Japanese institutions between January 2018 and August 2023. From this cohort, 178 patients with lymph node or distant metastases received either cytoreductive nephrectomy (CN group; n?=?72) or ICI therapy without cytoreductive nephrectomy (non-CN group; n?=?106) as first-line treatment.
Results: Median progression-free survival was 15.7?months, and median overall survival was 58.1?months. CN significantly improved OS, with the CN group's median OS not reached, compared to 29.6?months in the non-CN group (p?=?0.01). Deferred CN also showed improved survival outcomes. Poor prognostic factors for immediate CN included International Metastatic Renal Cell Carcinoma Database Consortium poor risk, sarcomatoid differentiation, and a high neutrophil-to-lymphocyte ratio.
Conclusions: We developed a prognostic model to guide patient selection for CN, emphasizing the need for personalized treatment strategies. en-copyright= kn-copyright= en-aut-name=NukayaTakuhisa en-aut-sei=Nukaya en-aut-mei=Takuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyodaShingo en-aut-sei=Toyoda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InokiLan en-aut-sei=Inoki en-aut-mei=Lan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujinoTakuya en-aut-sei=Tsujino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirasawaYosuke en-aut-sei=Hirasawa en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HashimotoTakeshi en-aut-sei=Hashimoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KomuraKazumasa en-aut-sei=Komura en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=FujitaKazutoshi en-aut-sei=Fujita en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OhnoYoshio en-aut-sei=Ohno en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShirokiRyoichi en-aut-sei=Shiroki en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=10 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=11 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=12 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=14 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=17 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=18 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= en-keyword=cytoreductive nephrectomy kn-keyword=cytoreductive nephrectomy en-keyword=IMDC classification kn-keyword=IMDC classification en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=neutrophil-to- lymphocyte ratio kn-keyword=neutrophil-to- lymphocyte ratio en-keyword=sarcomatoid differentiation kn-keyword=sarcomatoid differentiation END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=33014 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=iTRAQ-based quantitative proteomics reveals reduced expression of KRT19, KRT7, and PTGDS in cutaneous specimens after kidney transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Clinical improvement in pigmentation is frequently observed after kidney transplantation. However, the underlying molecular and histological mechanisms remain unclear. We conducted a study to quantify the skin color change using a handheld reflected light colorimeter and to investigate protein expression changes in the skin before and after kidney transplantation. Paired skin biopsies were obtained from three patients who underwent kidney transplantation before and one month after transplantation. Protein expression was analyzed using iTRAQ-based quantitative proteomics. Differentially expressed proteins were identified and visualized using hierarchical clustering and volcano plots. Histopathological evaluation included hematoxylin and eosin (H&E), Massonfs trichrome, and immunohistochemical (IHC) staining for keratin (KRT) 7, KRT19, and MelanA. Skin pigmentation of the arms, ankles, and abdomen had significant L-value improvement after kidney transplantation. Proteomic profiling identified 2148 proteins, with six proteins showing significant differential expression after transplantation. Among them, KRT7, KRT19, and prostaglandin D2 synthase (PTGDS) were significantly downregulated, potentially reflecting reduced epithelial stress and systemic inflammation. H&E and Massonfs trichrome staining revealed a post-transplantation reduction in dermal pigmentation and collagen content. IHC showed decreased KRT7, KRT19, and MelanA expression after transplantation. Our results suggest that targeting KRT or prostaglandin pathways may offer new treatments for ESRD-related skin symptoms. en-copyright= kn-copyright= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Inflammation and Immunity, Lerner Research Institute Cleveland Clinic kn-affil= affil-num=6 en-affil=Department of Inflammation and Immunity, Lerner Research Institute Cleveland Clinic kn-affil= affil-num=7 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Cutaneous manifestations kn-keyword=Cutaneous manifestations en-keyword=Keratin kn-keyword=Keratin en-keyword=Skin color kn-keyword=Skin color en-keyword=Pigmentation kn-keyword=Pigmentation en-keyword=Prostaglandin D2 synthase kn-keyword=Prostaglandin D2 synthase en-keyword=Renal transplantation kn-keyword=Renal transplantation en-keyword=Dialysis kn-keyword=Dialysis END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=17 article-no= start-page=6122 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250829 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Potential of Kidney Exchange Programs (KEPs) in Japan for Donor-Specific Antibody-Positive Kidney Transplants: A Questionnaire Survey on KEPs and a Multi-Institutional Study Conducting Virtual Cross-Matching Simulations en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To clarify the need for a kidney exchange program (KEP) in Japan by conducting a questionnaire survey on KEPs and simulated KEPs by virtual cross-matching based on past cases of transplantation avoidance. Methods: In addition to the content regarding KEPs, an electronic survey was conducted to investigate the number of cases of kidney transplant abandonment due to gimmunologicalh reasons over the past 10 years (2012?2021). Virtual cross-matching was conducted to simulate the feasibility of avoiding immunological risks and enabling kidney transplantation in patients who were previously unable to undergo the procedure. Results: The survey received responses from 107 facilities (response rate: 81.7%). In response to the question about the necessity of a KEP in Japan, 71 facilities (66.4%) indicated that KEPs are necessary. In addition, 251 living-donor kidney transplants were abandoned for gimmunologicalh reasons over the past decade (2012?2021). Among the 80 pairs for which detailed information was available, virtual cross-matching simulations showed that 37/80 pairs (46.3%) were donor-specific antibody (DSA)-negative for blood type-matched combinations, and 41/80 pairs (51.3%) were DSA-negative for blood type-incompatible transplants. Conclusions: The need for a KEP in Japan and its potential usefulness were demonstrated. en-copyright= kn-copyright= en-aut-name=ItoTaihei en-aut-sei=Ito en-aut-mei=Taihei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoMiki en-aut-sei=Ito en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AidaNaohiro en-aut-sei=Aida en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuriharaKei en-aut-sei=Kurihara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TeraoAkihiro en-aut-sei=Terao en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WataraiYoshihiko en-aut-sei=Watarai en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoMitsuru en-aut-sei=Saito en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KakuKeizo en-aut-sei=Kaku en-aut-mei=Keizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiiDaisuke en-aut-sei=Ishii en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SekiguchiSatoshi en-aut-sei=Sekiguchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YonedaTatsuo en-aut-sei=Yoneda en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UnagamiKohei en-aut-sei=Unagami en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TasakiMasayuki en-aut-sei=Tasaki en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwamotoHitoshi en-aut-sei=Iwamoto en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=TakahashiKazuhiro en-aut-sei=Takahashi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamanakaKazuaki en-aut-sei=Yamanaka en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SugimotoMikio en-aut-sei=Sugimoto en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NishikawaKouhei en-aut-sei=Nishikawa en-aut-mei=Kouhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SetoChikashi en-aut-sei=Seto en-aut-mei=Chikashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MuramatsuMasaki en-aut-sei=Muramatsu en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=AsaiToshihiro en-aut-sei=Asai en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=IwamiDaiki en-aut-sei=Iwami en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=YamadaYasutoshi en-aut-sei=Yamada en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YamanagaShigeyoshi en-aut-sei=Yamanaga en-aut-mei=Shigeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KomatsuTomonori en-aut-sei=Komatsu en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MiuraMasayoshi en-aut-sei=Miura en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NoharaTakahiro en-aut-sei=Nohara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=MaruyamaMichihiro en-aut-sei=Maruyama en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=MiyauchiYuki en-aut-sei=Miyauchi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=TanakaToshiaki en-aut-sei=Tanaka en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=NakamuraMichio en-aut-sei=Nakamura en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=HottaKiyohiko en-aut-sei=Hotta en-aut-mei=Kiyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KenmochiTakashi en-aut-sei=Kenmochi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=2 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=3 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=4 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=5 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=6 en-affil=Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital kn-affil= affil-num=7 en-affil=Division of Blood Purification, Akita University Hospital kn-affil= affil-num=8 en-affil=Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Urology, Kitasato University of Medicine kn-affil= affil-num=10 en-affil=Transplantation Surgery, Japan Community Healthcare Organization Sendai Hospital kn-affil= affil-num=11 en-affil=Unit of Dialysis, Department of Urology, Nara Medical University kn-affil= affil-num=12 en-affil=Organ Transplant Medicine, Tokyo Womenfs Medical University kn-affil= affil-num=13 en-affil=Division of Urology, Department of Regenerative & Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=14 en-affil=Department of Kidney Transplantation Surgery, Tokyo Medical University Hachioji Medical Center kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba kn-affil= affil-num=17 en-affil=Department of Urology, Osaka University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Urology, Faculty of Medicine, Adrenal Surgery and Renal Transplantation, Kagawa University kn-affil= affil-num=19 en-affil=Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Urology, Toyama Prefectural Central Hospital kn-affil= affil-num=21 en-affil=Department of Nephrology, Toho University Faculty of Medicine kn-affil= affil-num=22 en-affil=Department of Kidney Transplant and Dialysis, Osaka City General Hospital kn-affil= affil-num=23 en-affil=Division of Renal Surgery and Transplantation, Department of Urology, Jichi Medical University kn-affil= affil-num=24 en-affil=Department of Blood Purification, Kagoshima University Hospital kn-affil= affil-num=25 en-affil=Department of Transplant Surgery, Japanese Red Cross Kumamoto Hospital kn-affil= affil-num=26 en-affil=Department of Urology, Chukyo Hospital, Japan Community Healthcare Organization kn-affil= affil-num=27 en-affil=Department of Renal Transplantation Surgery and Urology, Sapporo Hokuyu Hospital kn-affil= affil-num=28 en-affil=Department of Urology, Kanazawa University Hospital kn-affil= affil-num=29 en-affil=Department of Frontier Surgery, Chiba University School of Medicine kn-affil= affil-num=30 en-affil=Department of Urology, Ehime University kn-affil= affil-num=31 en-affil=Department of Urology, Sapporo Medical University kn-affil= affil-num=32 en-affil=Department of Transplant Surgery, Tokai University School of Medicine kn-affil= affil-num=33 en-affil=Department of Renal and Genitourinary Surgery, Faculty of Medicine, Hokkaido University kn-affil= affil-num=34 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= en-keyword=kidney transplantation kn-keyword=kidney transplantation en-keyword=donor-specific antibodies kn-keyword=donor-specific antibodies en-keyword=kidney exchange program kn-keyword=kidney exchange program en-keyword=virtual cross-matching kn-keyword=virtual cross-matching END start-ver=1.4 cd-journal=joma no-vol=178 cd-vols= no-issue= article-no= start-page=106920 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=End-to-end time-dependent probabilistic assessment of landslide hazards using hybrid deep learning simulator en-subtitle= kn-subtitle= en-abstract= kn-abstract=Early warning detection of landslide hazards often requires real-time or near real-time predictions, which can be challenging due to the presence of multiple geo-uncertainties and time-variant external environmental loadings. The propagation of these uncertainties at the system level for understanding the spatiotemporal behavior of slopes often requires time-consuming numerical calculations, significantly hindering the establishment of an early warning system. This paper presents a hybrid deep learning simulator, which fuses parallel convolutional neural networks (CNNs) and long short-term memory (LSTM) networks through attention mechanisms, termed PCLA-Net, to facilitate time-dependent probabilistic assessment of landslide hazards. PCLA-Net features two novelties. First, it is capable of simultaneously handling both temporal and spatial information. CNNs specialize in interpreting spatial data, while LSTM excels in handling time-variant data. Coupled with two attention mechanisms, the two modules are combined to probabilistically predict the spatiotemporal behavior of slopes. Second, PCLA-Net realizes end-to-end predictions. In this paper, the Liangshuijing landslide in the Three Gorges Reservoir area of China is used to illustrate PCLA-Net. It is first validated followed by a comparison with existing techniques to demonstrate its improved predictive capabilities. The proposed PCLA-Net simulator can achieve the same level of accuracy with at least 50% reduction in computation resources. en-copyright= kn-copyright= en-aut-name=HuangMenglu en-aut-sei=Huang en-aut-mei=Menglu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraShin-ichi en-aut-sei=Nishimura en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShibataToshifumi en-aut-sei=Shibata en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangZe Zhou en-aut-sei=Wang en-aut-mei=Ze Zhou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Civil and Environmental Engineering, Okayama University kn-affil= affil-num=2 en-affil=Department of Civil and Environmental Engineering, Okayama University kn-affil= affil-num=3 en-affil=Department of Civil and Environmental Engineering, Okayama University kn-affil= affil-num=4 en-affil=Marie Sk?odowska-Curie Fellow, Department of Engineering, University of Cambridge kn-affil= en-keyword=Spatial variability kn-keyword=Spatial variability en-keyword=Time-dependent reliability kn-keyword=Time-dependent reliability en-keyword=Convolutional neural networks kn-keyword=Convolutional neural networks en-keyword=Long short-term memory networks kn-keyword=Long short-term memory networks en-keyword=Attention mechanisms kn-keyword=Attention mechanisms en-keyword=Landslide hazards kn-keyword=Landslide hazards END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=89 article-no= start-page=17364 end-page=17367 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=The direct photochemical cross-esterification of alcohols via site-selective C?H bromination site-selective C?H bromination en-subtitle= kn-subtitle= en-abstract= kn-abstract=We have developed a direct photochemical cross-esterification of alcohols that proceeds via the in situ generation of acyl bromides. The C?H bond of a benzyl alcohol is selectively activated by a bromo source under light irradiation, enabling the cross-esterification to afford a variety of functionalized esters. en-copyright= kn-copyright= en-aut-name=MiyamotoAtsuya en-aut-sei=Miyamoto en-aut-mei=Atsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakamuraHiroyoshi en-aut-sei=Takamura en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KadotaIsao en-aut-sei=Kadota en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaKenta en-aut-sei=Tanaka en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue= article-no= start-page=1682012 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Maternal circulating GPIHBP1 levels and neonatal outcomes in patients with gestational diabetes mellitus: a pilot study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: The prevalence of gestational diabetes mellitus (GDM) is significantly increasing. Hyperglycaemia and dyslipidaemia have been demonstrated to contribute to endothelial dysfunction linked to foetal?placental circulation. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) is crucial for the lipolytic processing of TG-rich lipoproteins through the anchoring of lipoprotein lipase (LPL). In this study, circulating GPIHBP1 levels during pregnancy were evaluated, and their associations with hypertriglyceridaemia and the perinatal outcomes of GDM were evaluated.
Methods: This study included 12 pregnant women with GDM and 21 pregnant women with normal glucose tolerance (NGT).
Results: No significant differences in obstetrical outcomes were detected between the two groups. In participants with NGT, circulating GPIHBP1 levels were markedly lower in the 3rd trimester than in the 2nd trimester and at delivery. In women with GDM, circulating GPIHBP1 levels were unchanged during the 3rd trimester, and circulating GPIHBP1 levels throughout the 3rd trimester were negatively correlated with neonatal birth weight percentile and umbilical venous pO2 (=-0.636, p=0.026; =-0.657, p=0.020).
Discussion: Our findings suggest a possible association between circulating GPIHBP1 levels and perinatal outcomes in patients with GDM. en-copyright= kn-copyright= en-aut-name=WatanabeMayu en-aut-sei=Watanabe en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KurookaNaoko en-aut-sei=Kurooka en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EtoEriko en-aut-sei=Eto en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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 Obstetrics and Gynecology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, 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= en-keyword=glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) kn-keyword=glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) en-keyword=gestational diabetes mellitus (GDM) kn-keyword=gestational diabetes mellitus (GDM) en-keyword=perinatal outcomes kn-keyword=perinatal outcomes en-keyword=placenta kn-keyword=placenta en-keyword=triglyceride (TG) kn-keyword=triglyceride (TG) END start-ver=1.4 cd-journal=joma no-vol=82 cd-vols= no-issue=10 article-no= start-page=1626 end-page=1637 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=Redefining AT1 Receptor PET Imaging: Introducing the Radiotracer [18F]DR29 en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND: AT1R (angiotensin II type 1 receptors) are central to the renin-angiotensin system and are involved in regulating blood pressure and renal physiology. This study introduces [18F]DR29, a fluorine-18-labeled radiotracer for positron emission tomography imaging, to enable noninvasive visualization of AT1R expression. Its potential applications in understanding AT1R-associated renal processes are explored in healthy and hypertensive rat models.
METHODS: Radiolabeling was established, and biodistribution studies were conducted on healthy Wistar rats with and without the AT1R antagonist candesartan and transporter inhibitors. Dynamic positron emission tomography imaging assessed tracer specificity, and feasibility for renal AT1R quantification was explored using a hypertensive rat model.
RESULTS: [18F]DR29 was radiolabeled with a yield of 36}6%. High kidney uptake was observed, significantly reduced by candesartan (kidney-to-blood ratio, 0.43}0.01 versus 4.54}1.59 in vehicle, where vehicle refers to saline without any treatment). Transporter inhibition protocols targeting organic anion transporting polypeptides (liver) and organic anion transporters (kidneys) successfully reduced radiotracer clearance, increasing the specific accumulation of [18F]DR29 in the kidneys and improving renal imaging contrast. Positron emission tomography imaging revealed rapid kidney uptake and stable retention over 2 hours. In hypertensive rats, kidney uptake was higher, aligning with AT1R expression levels.
CONCLUSIONS: These results support [18F]DR29 as a promising tool for the noninvasive evaluation of renal AT1R expression in healthy and diseased states. The findings lay the groundwork for clinical translation, offering potential applications in diagnosing and managing kidney-related diseases, including hypertension and other conditions involving AT1R dysregulation. en-copyright= kn-copyright= en-aut-name=ChenXinyu en-aut-sei=Chen en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraHiroyuki en-aut-sei=Kimura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KlimekKonrad en-aut-sei=Klimek en-aut-mei=Konrad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=M?hligSaskia en-aut-sei=M?hlig en-aut-mei=Saskia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Arias-LozaAnahi Paula en-aut-sei=Arias-Loza en-aut-mei=Anahi Paula kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=YagiYusuke en-aut-sei=Yagi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=RoweSteven P en-aut-sei=Rowe en-aut-mei=Steven P kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LapaConstantin en-aut-sei=Lapa en-aut-mei=Constantin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WernerRudolf A. en-aut-sei=Werner en-aut-mei=Rudolf A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=2 en-affil=Agency for Health, Safety and Environment, Kyoto University kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Goethe University Frankfurt, University Hospital, Clinic for Radiology and Nuclear Medicine, Department of Nuclear Medicine kn-affil= affil-num=5 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (DZHI), University Hospital W?rzburg kn-affil= affil-num=6 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (DZHI), University Hospital W?rzburg kn-affil= affil-num=7 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Molecular Imaging and Therapeutics, Department of Radiology, School of Medicine, University of North Carolina, Chapel Hill kn-affil= affil-num=10 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=11 en-affil=Department of Nuclear Medicine, LMU Hospital, Ludwig-Maximilians-University of Munich kn-affil= affil-num=12 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=angiotensin II type 1 receptor kn-keyword=angiotensin II type 1 receptor en-keyword=organic anion transporters kn-keyword=organic anion transporters en-keyword=organic anion transporting polypeptides kn-keyword=organic anion transporting polypeptides en-keyword=renal imaging kn-keyword=renal imaging en-keyword=renin-angiotensin system kn-keyword=renin-angiotensin system 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=Admission prognostic nutritional index predicts prolonged hospitalization in severe odontogenic deep neck infections en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives Severe odontogenic deep neck infections (DNIs) can be life threatening. This study investigated the nutritional status of affected patients and evaluated the usefulness of the Prognostic Nutritional Index (PNI) at admission in helping maxillofacial surgeons identify, at presentation, those likely to require extended hospitalization.
Methods A total of 112 patients treated for odontogenic deep neck abscesses and necrotizing soft tissue infections at five hospitals in Japan. Patients were included. Patients were categorized by length of hospitalization duration and factors associated with prolonged hospitalization were analyzed using propensity score matching to minimize bias. Spearmanfs rank correlation analysis was also performed to assess the relationship between PNI and hospitalization duration.
Results Fifty patients (44.6%) required hospitalization for more than 14 days. Multivariate analysis identified PNI???41.2 (odds ratio [OR]?=?2.79) and the presence of abscesses in multiple deep neck spaces (OR?=?2.76) as significant predictors of prolonged hospitalization. Propensity score analysis confirmed the significant association between PNI and length of hospitalization duration (P?=?0.048). In addition, Spearmanfs rank correlation coefficient was r?=???0.471 (P? Conclusion The admission PNI may serve as a useful adjunctive indicator for predicting prolonged hospitalization in patients with severe odontogenic DNIs, as it reflects both nutritional status and systemic inflammation. en-copyright= kn-copyright= en-aut-name=IwataEiji en-aut-sei=Iwata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikutaShogo en-aut-sei=Kikuta en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanekoNaoki en-aut-sei=Kaneko en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKotaro en-aut-sei=Sato en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitagawaNorio en-aut-sei=Kitagawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuoKatsuhisa en-aut-sei=Matsuo en-aut-mei=Katsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SameshimaJunsei en-aut-sei=Sameshima en-aut-mei=Junsei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TachibanaAkira en-aut-sei=Tachibana en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawanoShintaro en-aut-sei=Kawano en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KusukawaJingo en-aut-sei=Kusukawa en-aut-mei=Jingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AkashiMasaya en-aut-sei=Akashi en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=4 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=9 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Kakogawa Central City Hospital kn-affil= affil-num=11 en-affil=Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University kn-affil= affil-num=12 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=13 en-affil=Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=15 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Odontogenic deep neck infections kn-keyword=Odontogenic deep neck infections en-keyword=Nutrition status kn-keyword=Nutrition status en-keyword=Prognostic nutritional index kn-keyword=Prognostic nutritional index en-keyword=Prolonged hospitalization kn-keyword=Prolonged hospitalization en-keyword=Multiple spaces with abscess kn-keyword=Multiple spaces with abscess 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=20251104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optogenetic Cancer Therapy Using the Light-Driven Outward Proton Pump Rhodopsin Archaerhodopsin-3 (AR3) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Medicines used for cancer treatment often cause serious side effects by damaging normal cells due to nonspecific diffusion. To address this issue, we previously developed an optical method to induce apoptotic cell death via intracellular pH alkalinization using the outward proton pump rhodopsin, Archaerhodopsin-3 (AR3) in various noncancer model cells in vitro and in vivo. In this study, we applied this method to cancer cells and tumors to evaluate its potential as an anticancer therapeutic strategy. First, we confirmed that AR3-expressing murine cancer cell lines (MC38, B16F10) showed apoptotic cell death upon green light irradiation, as indicated by increased levels of cell death and apoptosis-related markers. Next, we established stable AR3-expressing MC38 and B16F10 cells by using viral vectors. When these AR3-expressing cells were subcutaneously transplanted into C57BL/6 mice, the resulting tumors initially grew at a rate comparable to that of control tumors lacking AR3 expression or light stimulation. However, upon green light irradiation, AR3-expressing tumors exhibited either a marked reduction in size or significantly suppressed growth, accompanied by the induction of apoptosis signals and decreased proliferation signals. These results demonstrate that AR3-mediated cell death has potent antitumor effects both in vitro and in vivo. This optical method thus holds promise as a novel cancer therapy with potentially reduced side effects. en-copyright= kn-copyright= en-aut-name=NakaoShin en-aut-sei=Nakao en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=SatoKeita en-aut-sei=Sato en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KemmotsuNaoya en-aut-sei=Kemmotsu en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=281 cd-vols= no-issue= article-no= start-page=111174 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=N-terminal domains and site-specific glycosylation regulate the secretion of avian melanocortin inverse agonists, agouti signaling protein (ASIP) and agouti-related protein (AGRP) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Agouti signaling protein (ASIP) and agouti-related protein (AGRP) are paralogous inverse agonists of melanocortin receptors with distinct physiological roles, but their structural and biochemical properties in birds remain poorly understood. Here, we characterized chicken ASIP and AGRP proteins. Analysis of available sequences revealed that a motif resembling the mammalian proprotein convertase 1/3 (PC1/3, also known as PCSK1) cleavage site is conserved across a broad range of avian orders, but Western blot analysis of transfected Chinese hamster ovary (CHO-K1) cells and chicken hypothalamus detected no cleavage, suggesting that avian AGRP may not be post-translationally processed at this site. Chicken ASIP mRNA contains an in-frame upstream ATG (uATG) and a putative N-linked glycosylation site at Asn-42, both conserved across multiple avian orders. Overexpression in CHO-K1 cells showed that ASIP translated from either ATG produces a mature protein of the same size that is N-glycosylated at Asn-42 and exhibits markedly lower secretion efficiency than AGRP. Domain-swapping experiments revealed that the N-terminal domain reduces secretion, whereas a naturally occurring ASIP-b variant with an additional N-glycan at Asn-47 shows enhanced secretion. Proteasome inhibition increased intracellular ASIP, and endoglycosidase H (Endo H) sensitivity indicated endoplasmic reticulum (ER) retention, suggesting that the N-terminal domain limits secretion via ER-associated proteasomal degradation. These findings reveal species-specific post-translational regulation of avian melanocortin inverse agonists, in which N-terminal features and site-specific N-glycosylation determine secretion efficiency, likely contributing to their distinct roles in pigmentation and hypothalamic energy balance. en-copyright= kn-copyright= en-aut-name=FukuchiHibiki en-aut-sei=Fukuchi en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeRyoya en-aut-sei=Watanabe en-aut-mei=Ryoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IidaYuna en-aut-sei=Iida en-aut-mei=Yuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakanoSaya en-aut-sei=Nakano en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MizutaniAya en-aut-sei=Mizutani en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AboTatsuhiko en-aut-sei=Abo en-aut-mei=Tatsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AizawaSayaka en-aut-sei=Aizawa en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiSakae en-aut-sei=Takeuchi en-aut-mei=Sakae 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=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, 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=Graduate School of Natural Science and Technology, 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= en-keyword=Agouti signaling protein kn-keyword=Agouti signaling protein en-keyword=Agouti-related protein kn-keyword=Agouti-related protein en-keyword=Avian melanocortin inverse agonists kn-keyword=Avian melanocortin inverse agonists en-keyword=Post-translational modification kn-keyword=Post-translational modification en-keyword=N-linked glycosylation kn-keyword=N-linked glycosylation en-keyword=Protein secretion kn-keyword=Protein secretion END start-ver=1.4 cd-journal=joma no-vol=99 cd-vols= no-issue=10 article-no= start-page=e00984-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Human herpesvirus 6B U65 binds to histone proteins and suppresses interferon production en-subtitle= kn-subtitle= en-abstract= kn-abstract=Human herpesvirus 6B (HHV-6B), a member of the Betaherpesvirinae subfamily, is a T-lymphotropic virus that causes exanthem subitum and has been implicated in neuroinflammatory conditions such as multiple sclerosis. The tegument proteins, which are characteristic of herpesviruses, play a crucial role in the envelopment of virions and evasion of host immune defenses, such as the interferon (IFN) signaling pathway. However, the precise mechanisms through which the HHV-6B tegument proteins modulate the IFN pathway are not yet fully understood. In this study, we identified a novel function of the HHV-6B tegument protein U65 as an inhibitor of IFN production. Additionally, two host histone proteins, hCG_2039566 (H2ACG) and H2AC7, were identified as positive regulators of innate immune pathways. U65 interacts with H2ACG and H2AC7, impairing their ability to promote the IFN pathway. Furthermore, we demonstrated that U65 plays critical roles during HHV-6B infection. This study highlights a critical strategy employed by HHV-6B to evade immune defenses, shedding light on its mechanisms for counteracting host responses. en-copyright= kn-copyright= en-aut-name=LiHaokun en-aut-sei=Li en-aut-mei=Haokun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgawaHirohito en-aut-sei=Ogawa en-aut-mei=Hirohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TengDa en-aut-sei=Teng en-aut-mei=Da kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkameYuki en-aut-sei=Okame en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NambaHikaru en-aut-sei=Namba en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HondaTomoyuki en-aut-sei=Honda en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=HHV-6B kn-keyword=HHV-6B en-keyword=interferons kn-keyword=interferons en-keyword=histone kn-keyword=histone en-keyword=tegument kn-keyword=tegument en-keyword=U65 kn-keyword=U65 END start-ver=1.4 cd-journal=joma no-vol=136 cd-vols= no-issue=10 article-no= start-page=lxaf217 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gut dysbiosis allows foodborne salmonella colonization in edible crickets: a probiotic strategy for enhanced food safety en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Edible insects, including crickets, represent a promising protein source, yet concerns over foodborne pathogens limit consumer acceptance. This study investigated whether gut microbiota modulates colonization by Salmonella enterica subsp. enterica serovar Enteritidis (SE) in the two-spotted cricket (Gryllus bimaculatus).
Methods and Results: Under standard conditions, SE was undetectable in crickets despite prolonged exposure; however, antibiotic-induced dysbiosis enabled stable SE colonization. Long-read 16S rRNA sequencing revealed significant microbiota shifts, notably a reduction in Lactococcus garvieae. In vitro assays showed strong inhibitory effects of L. garvieae against SE, and supplementation of dysbiotic crickets with L. garvieae reduced SE colonization by ?1000-fold.
Conclusions: The native cricket gut microbiota, especially L. garvieae, plays a protective role against SE colonization. Enhancing beneficial gut bacteria could mitigate pathogen risks and promote edible insects as a sustainable protein. en-copyright= kn-copyright= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsushitaOsamu en-aut-sei=Matsushita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokotaKenji en-aut-sei=Yokota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BandoTetsuya en-aut-sei=Bando en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=food safety kn-keyword=food safety en-keyword=edible crickets kn-keyword=edible crickets en-keyword=Salmonella kn-keyword=Salmonella en-keyword=Lactococcus kn-keyword=Lactococcus en-keyword=probiotics kn-keyword=probiotics en-keyword=microbiome kn-keyword=microbiome END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=11 article-no= start-page=1680 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251029 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Kidney Organoids: Current Advances and Applications en-subtitle= kn-subtitle= en-abstract= kn-abstract=Kidney organoids, derived from stem cells, including pluripotent stem cells and adult progenitor cells, have been reported as three-dimensional in vitro models that reflect key aspects of kidney development, structure, and function. Advances in differentiation protocols and tissue engineering have enabled the generation of organoids that exhibit nephron-like structures, including glomerular and tubular structures. Kidney organoids have been widely applied in several directions, including disease modeling and therapeutic screening, drug nephrotoxicity evaluation, and regenerative medicine. In particular, kidney organoids offer a promising platform for studying genetic kidney diseases, such as polycystic kidney disease and congenital anomalies of the kidney and urinary tract (CAKUT), by allowing patient-specific modeling for the analysis of pathophysiology and therapeutic screening. Despite several current limitations, such as incomplete maturation, lack of full nephron segmentation, and variability between protocols and cell conditions, further technological innovations such as microfluidics and bioengineering may refine kidney organoid systems. This review highlights recent advances in kidney organoid research, outlines major applications, and discusses future directions to enhance their physiological relevance, functional maturity, and translational integration into preclinical and clinical nephrology. 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=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 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 Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=kidney organoid kn-keyword=kidney organoid en-keyword=stem cell kn-keyword=stem cell en-keyword=disease modeling kn-keyword=disease modeling en-keyword=drug toxicity kn-keyword=drug toxicity en-keyword=drug screening kn-keyword=drug screening en-keyword=regenerative medicine kn-keyword=regenerative medicine END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page=e92587 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250917 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Intranasal Administration of Semaphorin 3A Inhibitor in a Mouse Model of Olfactory Disorder en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the effects of intranasal administration of a semaphorin 3A inhibitor (Sema3A-I) in a mouse model of olfactory disorder, where olfactory sensory neuron (OSN) axons had been severely damaged. We performed axotomy (transection of OSN axons) of the OSNs in mice and administered Sema3A?I intranasally to seven mice and saline to another seven mice. Following treatment, we assessed the thickness of the olfactory epithelium and the regeneration ratio of OSN axons. Intranasal administration of Sema3A-I did not significantly promote OSN regeneration, axonal outgrowth, or improve axonal projection compared to saline administration. Although Sema3A-I administration showed some promotion of axonal outgrowth, the difference was not statistically significant. Continuous subcutaneous administration of Sema3A-I in rats after axotomy promotes OSN regeneration and axonal outgrowth. Given that intranasal administration is minimally invasive, we believe that it may still be a feasible route when combined with additional treatment strategies. Further investigation into administration methods and therapeutic combinations is warranted. en-copyright= kn-copyright= en-aut-name=MuraiAya en-aut-sei=Murai en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NodaMinori en-aut-sei=Noda en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=TakaharaJunko en-aut-sei=Takahara en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Technical Support for Medical Science, Department of Comprehensive Technical Solutions, Okayama University kn-affil= affil-num=5 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Otolaryngology - Head and Neck Surgery, Okayama University kn-affil= en-keyword=axon growth kn-keyword=axon growth en-keyword=intranasal administration kn-keyword=intranasal administration en-keyword=olfactory disorder kn-keyword=olfactory disorder en-keyword=olfactory sensory neurons kn-keyword=olfactory sensory neurons en-keyword=semaphorin3a kn-keyword=semaphorin3a END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=8 article-no= start-page=e89864 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Higher Liver Fibrosis-4 Index Is Associated With More Severe Hearing Loss in Idiopathic Sudden Sensorineural Hearing Loss en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Liver fibrosis is an important medical issue increasing over time in developed countries.
Aims/objectives
This study aimed to investigate whether liver fibrosis, as indicated by routine blood test parameters, influences the risk and severity of idiopathic sudden sensorineural hearing loss (ISSNHL).
Material and methods
Sixty-six patients with ISSNHL and 198 patients with benign parotid gland tumors (BPTs) (controls) were enrolled. Indices for liver fibrosis (Liver Fibrosis-4 index (FIB-4 index) and aspartate aminotransferase-to-platelet ratio index (APRI)) were calculated from the blood laboratory data. The pure tone average (PTA) was calculated as the mean of hearing levels at the six frequencies at the onset of ISSNHL. Severe hearing loss was defined as PTA?60 decibels Hearing Level (dB HL).
Results
In risk evaluation, the FIB-4 index did not differ significantly between ISSNHL patients and controls. Regarding the severity of ISSNHL, the FIB-4 index was significantly higher in ISSNHL patients with severe hearing loss than in those with PTA<60 dB HL (P<0.05) on univariate comparison. After adjusting for age, sex, and indices of inflammation, both the FIB-4 index and APRI showed a significant association with severe hearing loss (odds ratio (OR): 5.9, 95% confidence interval (CI): 1.3-25.7, and OR: 2.2, 95% CI: 1.1-4.7).
Conclusions and significance
Higher liver fibrosis indices (FIB-4 index and APRI), derived from routine blood laboratory data, are associated with a more severe phenotype of ISSNHL. en-copyright= kn-copyright= en-aut-name=MaedaYukihide en-aut-sei=Maeda en-aut-mei=Yukihide 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=OmichiRyotaro en-aut-sei=Omichi en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= affil-num=1 en-affil=Department of Otolaryngology-Head and Neck Surgery, 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 Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=aspartate aminotransferase-to-platelet ratio index kn-keyword=aspartate aminotransferase-to-platelet ratio index en-keyword=audiometry kn-keyword=audiometry en-keyword=fatty liver disease kn-keyword=fatty liver disease en-keyword=incidence kn-keyword=incidence en-keyword=liver fibrosis-4 index kn-keyword=liver fibrosis-4 index en-keyword=severity kn-keyword=severity en-keyword=sudden hearing loss kn-keyword=sudden hearing loss END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=10 article-no= start-page=1483 end-page=1493 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=Biologics and Small]Molecule Therapies in Netherton Syndrome: A Comprehensive Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Netherton syndrome (NS) is a rare congenital ichthyosis caused by loss-of-function mutations in the SPINK5 gene, leading to defective expression of the serine protease inhibitor LEKTI. Dysregulated epidermal protease activity results in impaired skin barrier function and chronic inflammation, accompanied by complex immune profiles. NS patients commonly show activation of the inflammatory axis, centered on IL-17 and IL-36, in the skin and blood, and show a psoriasis-like shift to Th17. Conversely, the immune profile differs depending on the clinical type, with ichthyosis linearis circumflexa type characterized by complement activation and Th2-type allergic responses, and scaly erythroderma type characterized by a type I IFN signature and Th9-type allergic responses. While symptomatic treatments such as emollients and topical corticosteroids have been the mainstay of care, recent advances have opened new therapeutic avenues involving biologic agents and oral small-molecule immunomodulators. This review provides a comprehensive overview of the current clinical landscape and future directions of biologics (e.g., dupilumab, secukinumab, ustekinumab) and small-molecule therapies (e.g., JAK inhibitors such as tofacitinib, baricitinib, and upadacitinib) in the treatment of NS. Though evidence remains limited to case reports and small series, preliminary data suggest that cytokine-targeted interventions?particularly those inhibiting IL-4, IL-13, IL-17, IL-36, and JAK pathways?may offer tangible clinical benefits. Well-designed clinical trials and mechanistic investigations are crucial to establishing their place in NS management. en-copyright= kn-copyright= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MukaiTomoyuki en-aut-sei=Mukai en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SunagawaKo en-aut-sei=Sunagawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HasuiKen]ichi en-aut-sei=Hasui en-aut-mei=Ken]ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaAnri en-aut-sei=Morita en-aut-mei=Anri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=27 article-no= start-page=6557 end-page=6563 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=Fluorescence detection of DNA with a single-base mismatch by a Tm-independent peptide nucleic acid (PNA) twin probe en-subtitle= kn-subtitle= en-abstract= kn-abstract=There is a need to develop efficient methods for detecting target nucleic acids to enable the rapid diagnosis and early treatment of diseases. We previously demonstrated that a peptide nucleic acid (PNA) twin probe, consisting of two PNAs each containing a fluorescent dye, with pyrene at one end, detects target DNA sequence-specifically through pyrene excimer emission. In this study, to advance the development of this probe system, we further investigated the fluorescence properties of the PNA twin probe P1 and P2, and found that the excimer fluorescence was significantly reduced when a mismatched base in the DNA sequence was present at the site of P1 closest to the pyrene. In other words, this probe was found to detect single-base mismatches without taking into account the thermal stability of the PNA/DNA hybrid. The detection limit of this PNA twin probe for the single-base-mismatched DNA was 2.7 nM. In the future, this probe should lead to a method to detect point mutations in endogenous nucleic acids within cells. en-copyright= kn-copyright= en-aut-name=IshiiKoki en-aut-sei=Ishii en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigetoHajime en-aut-sei=Shigeto en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamuraShohei en-aut-sei=Yamamura en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImaiYoshitane en-aut-sei=Imai en-aut-mei=Yoshitane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KitamatsuMizuki en-aut-sei=Kitamatsu en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=2 en-affil=Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=3 en-affil=Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=4 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Applied Chemistry, Kindai University 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=18 cd-vols= no-issue=10 article-no= start-page=e70318 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effectiveness of Statins for Oxaliplatin]Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ??2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching. However, among the matched patients with CRC (n?=?510), statin use was associated with a significantly lower incidence of Grade ??2 OIPN than no statin use (19.8% vs. 28.3%, respectively; p?=?0.029). Our findings indicate that statins may protect against OIPN in patients with CRC. en-copyright= kn-copyright= en-aut-name=TakechiKenshi en-aut-sei=Takechi en-aut-mei=Kenshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawashiriTakehiro en-aut-sei=Kawashiri en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MineKeisuke en-aut-sei=Mine en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UshioSoichiro en-aut-sei=Ushio en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HidaNoriko en-aut-sei=Hida en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MomoKenji en-aut-sei=Momo en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchiyamaMasanobu en-aut-sei=Uchiyama en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaMami en-aut-sei=Uchida en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaMamoru en-aut-sei=Tanaka en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HidakaNoriaki en-aut-sei=Hidaka en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasuiHideki en-aut-sei=Yasui en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UedaMasahiro en-aut-sei=Ueda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiRyohei en-aut-sei=Fujii en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HashimotoMisaki en-aut-sei=Hashimoto en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakamotoYasutaka en-aut-sei=Sakamoto en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UyamaKana en-aut-sei=Uyama en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HanaiYuki en-aut-sei=Hanai en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TsuboyaAyaka en-aut-sei=Tsuboya en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SuzukiKeisuke en-aut-sei=Suzuki en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KamiyamaNaoya en-aut-sei=Kamiyama en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HagiwaraHiromi en-aut-sei=Hagiwara en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OkadaNaoto en-aut-sei=Okada en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Research and Development, Graduate School of Pharmacy, SHOWA Medical University kn-affil= affil-num=7 en-affil=Department of Hospital Pharmaceutics, Graduate School of Pharmacy, SHOWA Medical University kn-affil= affil-num=8 en-affil=Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University kn-affil= affil-num=9 en-affil=Department of Pharmacy, Fukuoka University Hospital kn-affil= affil-num=10 en-affil=Division of Pharmacy, Ehime University Hospital kn-affil= affil-num=11 en-affil=Division of Pharmacy, Ehime University Hospital kn-affil= affil-num=12 en-affil=Center for Clinical Research, Hamamatsu University Hospital kn-affil= affil-num=13 en-affil=Faculty of Pharmaceutical Sciences, Setsunan University kn-affil= affil-num=14 en-affil=Department of Pharmacy, Kansai Medical University Hospital kn-affil= affil-num=15 en-affil=Department of Pharmacy, Kansai Medical University Hospital kn-affil= affil-num=16 en-affil=Department of Pharmacy, Yokohama City University Hospital kn-affil= affil-num=17 en-affil=Department of Pharmacy, Yokohama City University Hospital kn-affil= affil-num=18 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= affil-num=19 en-affil=Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University kn-affil= affil-num=20 en-affil=Department of Pharmacy, Kawasaki Municipal Tama Hospital kn-affil= affil-num=21 en-affil=Innovation Center for Translational Research, National Center for Geriatrics and Gerontology kn-affil= affil-num=22 en-affil=Asahikawa Medical University Hospital kn-affil= affil-num=23 en-affil=Nagoya City University Hospital kn-affil= affil-num=24 en-affil=Pharmacy Department, Yamaguchi University Hospital kn-affil= affil-num=25 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=26 en-affil=Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences kn-affil= en-keyword=cancer kn-keyword=cancer en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=oxaliplatin kn-keyword=oxaliplatin en-keyword=peripheral neuropathy kn-keyword=peripheral neuropathy en-keyword=statins kn-keyword=statins END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=6 article-no= start-page=738 end-page=748 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=Risk of Heart Failure Hospitalization in Patients Treated With Osimertinib en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Osimertinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, is used to treat patients with epidermal growth factor receptor?mutant non?small-cell lung cancer. Although osimertinib has been linked to heart failure (HF), detailed risk estimates remain unclear.
Objectives The aim of this study was to examine the association between osimertinib use and HF hospitalization.
Methods In this retrospective cohort study using a large-scale Japanese claims database, patients diagnosed with lung cancer between April 2008 and December 2021 who received cancer therapy were identified. Patients were categorized into osimertinib and control groups according to treatment received. The incidence of HF hospitalization during the treatment period was compared between the groups. Multivariable analyses were performed before and after propensity score matching.
Results The osimertinib and control groups included 11,391 and 108,144 patients, respectively. Among the entire cohort, the median age was 70 years (Q1-Q3: 64-76 years), and the median follow-up duration was 173 days (Q1-Q3: 73-448 days). The incidence of HF hospitalization was 9.9 and 4.1 cases per 1,000 person-years in the osimertinib and control groups, respectively. In multivariable analysis, osimertinib was associated with a higher risk for HF hospitalization than control therapy (subdistribution HR: 2.56; 95% CI: 2.07-3.18; P < 0.001). This association remained significant after propensity score matching (subdistribution HR: 2.29; 95% CI: 1.62-3.24; P < 0.001).
Conclusions Osimertinib use was associated with an increased risk for HF hospitalization. Cardiac function should be closely monitored in patients receiving osimertinib. en-copyright= kn-copyright= en-aut-name=TatebeYasuhisa en-aut-sei=Tatebe en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaYuta en-aut-sei=Tanaka en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ManabeYohei en-aut-sei=Manabe en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkanoShinobu en-aut-sei=Okano en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HigashionnaTsukasa en-aut-sei=Higashionna en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurakawaKiminaka en-aut-sei=Murakawa en-aut-mei=Kiminaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= en-keyword=adverse events kn-keyword=adverse events en-keyword=cardiotoxicity kn-keyword=cardiotoxicity en-keyword=epidermal growth factor receptor tyrosine kinase inhibitor kn-keyword=epidermal growth factor receptor tyrosine kinase inhibitor en-keyword=heart failure kn-keyword=heart failure en-keyword=lung cancer kn-keyword=lung cancer en-keyword=pharmacotherapy kn-keyword=pharmacotherapy en-keyword=propensity score matching kn-keyword=propensity score matching 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=20250912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiological assessment of dissected cervical lymph nodes in level III affected by the area of supraomohyoid neck dissection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To compare the number of dissected cervical lymph nodes in the anatomical level III with that in supraomohyoid neck dissection (SOHND) level III affected by the anatomical relationship between the omohyoid muscle and cricoid cartilage using contrast-enhanced CT (CE-CT) images to assess the validity of the current SOHND.
Methods: CE-CT images of the patients who suffered from malignant tumours in the oral and maxillofacial regions were reviewed. The number of cervical lymph nodes both in the anatomical level III (area between the centre of the inferior border of the hyoid bone [HB] and the inferior border of the cricoid cartilage [CC]) and SOHND level III (area between HB and the intersection of the omohyoid muscle and internal jugular vein [OM-IJ]) were recorded, respectively.
Results: The rate of patients whose number of lymph nodes in level III was affected by the positional relationship between the OM-IJ and CC was almost equal in males and females. As for the patients with OM-IJ below the CC, the number of lymph nodes in SOHND level III increased from that of anatomical level III. Females showed significantly higher values than males (P? Conclusions: The number of dissected cervical lymph nodes differed between the SOHND dissection area and levels I, II, and III. In most cases, SOHND dissects more cervical lymph nodes, especially in female patients. en-copyright= kn-copyright= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhyamaYoshio en-aut-sei=Ohyama en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsushitaYuki en-aut-sei=Matsushita en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TubbsR Shane en-aut-sei=Tubbs en-aut-mei=R Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitagawaNorio en-aut-sei=Kitagawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawazuToshiyuki en-aut-sei=Kawazu en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HisatomiMiki en-aut-sei=Hisatomi en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkadaShunsuke en-aut-sei=Okada en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujikuraMamiko en-aut-sei=Fujikura en-aut-mei=Mamiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YanagiYoshinobu en-aut-sei=Yanagi en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=5 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=6 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Clinical Anatomy Research Association in Oral and Maxillofacial Surgery kn-affil= en-keyword=omohyoid muscle kn-keyword=omohyoid muscle en-keyword=CT kn-keyword=CT en-keyword=neck dissection kn-keyword=neck dissection en-keyword=cervical lymph nodes kn-keyword=cervical lymph nodes en-keyword=cancer kn-keyword=cancer 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=20251020 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Coupling effects of biochar and sediment microbial fuel cells on CH4 and CO2 emissions from straw-amended paddy soil en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The independent incorporation of biochar and sediment microbial fuel cells (SMFCs) into paddy soil has been shown to reduce methane (CH4) emissions. However, the application of rice straw into paddy soil enhances the availability of labile carbon that stimulates methanogen growth, counteracting the mitigation effects of both methods. This study, therefore, aimed to investigate the effect of coupling biochar and SMFC on CH4 and CO2 emissions from straw-amended paddy soil.
Materials and methods Single chamber SMFC setups constructed using acrylic columns (height, 25 cm; inner diameter, 9 cm) with six treatments were established using soil amended with 0% (0BC), 1% (1BC), and 2% (2BC) biochar: with and without SMFC conditions. Stainless steel mesh (15?~?3 cm) and graphite felt (6?~?5 cm) were used as anode and cathode materials, respectively.
Results Cumulative emission of CH4 in the 0BC treatment with SMFC was 39% less than in that without SMFC. Biochar addition and SMFC operation together further reduced CH4 emission by 57% and 60% in 1BC and 2BC treatments, respectively, compared to that in the 0BC treatment without SMFC operation. The relative abundance of microbial communities indicated methane-oxidizing bacteria were enriched in the presence of biochar and hydrogenotrophic Methanoregula were suppressed by SMFC operation. This suggested that SMFC mainly inhibited CH4 production by outcompeting hydrogenotrophic archaea.
Conclusion The use of biochar made from leftover rice straw has an interactive effect on SMFC operation and both methods can be used to reduce CH4 emission from straw-amended paddy soil. en-copyright= kn-copyright= en-aut-name=BekeleAdhena Tesfau en-aut-sei=Bekele en-aut-mei=Adhena Tesfau kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaMorihiro en-aut-sei=Maeda en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakaharaNozomi en-aut-sei=Nakahara en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashiguchiAyumi en-aut-sei=Hashiguchi en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SomuraHiroaki en-aut-sei=Somura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkaoSatoshi en-aut-sei=Akao en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanoChiyu en-aut-sei=Nakano en-aut-mei=Chiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Science and Engineering, Doshisha University kn-affil= affil-num=7 en-affil=Department of Comprehensive Technical Solutions, Okayama University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=Electrogenesis kn-keyword=Electrogenesis en-keyword=Methane oxidation kn-keyword=Methane oxidation en-keyword=Pyrolysis kn-keyword=Pyrolysis en-keyword=Paddy field kn-keyword=Paddy field en-keyword=Methanogens kn-keyword=Methanogens END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e95647 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251029 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Histopathological Study of Regenerative Endodontic Therapy on an Immature Mandibular Second Premolar With Pulp Necrosis: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Regenerative endodontic therapy (revascularization) for immature permanent teeth with pulp necrosis and/or apical periodontitis is an effective treatment to promote root maturation. Previous histological studies have reported the formation of cementoid or osteoid tissue and periodontal ligament-like tissue within the root canals. This case report presents the histopathological findings of a human immature permanent tooth with pulp necrosis following revascularization.

A 11-year-old male patient presented with tenderness on biting and the formation of a sinus tract in the mandibular right second premolar (tooth #29), diagnosed as pulp necrosis with symptomatic apical periodontitis. Revascularization was performed using calcium hydroxide as an intracanal medicament, with reference to the American Association of Endodontists (AAE) 2018 Position Paper on Regenerative Endodontics. At the 12-month follow-up, radiographs showed thickening of the canal walls, apical narrowing, root elongation, and recovery of pulp sensibility. The tooth was later extracted for orthodontic reasons at 42 months and processed for histological examination.

Histological evaluation revealed cementum-like hard tissue continuous with the existing dentin in the apical region, suggesting apical closure. In contrast, the coronal portion showed less mature cementum-like tissue accompanied by loose connective tissue and neovascularization. These findings indicate that revascularization with calcium hydroxide can induce the formation of cementum-like and dentin-like tissues with vascular regeneration in immature permanent teeth with pulp necrosis. en-copyright= kn-copyright= en-aut-name=SakoHidefumi en-aut-sei=Sako en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=calcium hydroxide kn-keyword=calcium hydroxide en-keyword=immature permanent teeth kn-keyword=immature permanent teeth en-keyword=pulp necrosis kn-keyword=pulp necrosis en-keyword=regenerative endodontic therapy kn-keyword=regenerative endodontic therapy en-keyword=revascularization kn-keyword=revascularization END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=10 article-no= start-page=107001 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251028 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multichannel topological elastic waveguide in a multilayer Kagome phononic crystal en-subtitle= kn-subtitle= en-abstract= kn-abstract=By examining the geometric characteristics of various boundaries formed within the Kagome phononic lattice and vertically stacking the lattices, we designed an elastic waveguide that enables selective propagation of topologically protected edge modes across layers in a bilayer system. This layer-selective transmission is manifested as polarized boundary modes that appear in phononic dispersions of the systems incorporating the bridge, zigzag, and armchair boundaries. We numerically demonstrated that efficient elastic layer converters and splitters can be designed, thereby paving the way for the practical development of three-dimensional elastic-wave devices. en-copyright= kn-copyright= en-aut-name=HataYusuke en-aut-sei=Hata en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsurutaKenji en-aut-sei=Tsuruta en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Electrical and Electronic Engineering, Okayama University kn-affil= affil-num=2 en-affil=Department of Electrical and Electronic Engineering, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=6 article-no= start-page=836 end-page=849 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251028 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=C1orf50 Accelerates Epithelial-Mesenchymal Transition and the Cell Cycle of Hepatocellular Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with limited treatment options and a poor prognosis in advanced stages. To identify novel biomarkers and therapeutic targets, we investigated the role of chromosome 1 open reading frame 50 (C1orf50), a gene with a previously uncharacterized function in HCC.
Materials and Methods: We performed a comprehensive transcriptome data analysis of the human hepatocellular carcinoma project from The Cancer Genome Atlas (TCGA) and subsequently validated the oncogenic roles of C1orf50 using HCC cell lines.
Results: Using transcriptomic and clinical data from TCGA, we stratified 355 primary HCC samples based on C1orf50 expression levels. Patients with high C1orf50 expression exhibited significantly shorter overall survival, suggesting its association with aggressive tumor behavior. Differential expression and enrichment analyses revealed that C1orf50-high tumors were enriched in oncogenic pathways, including epithelial-mesenchymal transition (EMT), cell cycle activation, and stemness-related properties. Transcriptional regulatory network analysis detected 456 significantly dysregulated regulons, including ZEB1/2 and E2F2, key drivers of EMT and cell cycle, in the C1orf50-high group. In addition, we observed increased YAP1/TAZ signaling, further linking C1orf50 to stemness and therapeutic resistance. Functional data from CRISPR-based dependency screening suggested that several transcription factors up-regulated in the C1orf50-high state, such as ZBTB11 and CTCE, are essential for the survival of HCC cells. These findings indicate potential therapeutic vulnerabilities and support the rationale for targeting C1orf50-associated pathways.
Conclusion: C1orf50 is a novel biomarker of poor prognosis in HCC and a key regulator of oncogenic features such as EMT, cell cycle progression, and stemness. This study highlights the therapeutic potential of targeting C1orf50-related networks in aggressive subtypes of liver cancer. en-copyright= kn-copyright= en-aut-name=TANAKAATSUSHI en-aut-sei=TANAKA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OTANIYUSUKE en-aut-sei=OTANI en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MAEKAWAMASAKI en-aut-sei=MAEKAWA en-aut-mei=MASAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ROGACHEVSKAYAANNA en-aut-sei=ROGACHEVSKAYA en-aut-mei=ANNA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PE?ATIRSO en-aut-sei=PE?A en-aut-mei=TIRSO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CHINVANESSA D. en-aut-sei=CHIN en-aut-mei=VANESSA D. 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=ROEHRLMICHAEL H. en-aut-sei=ROEHRL en-aut-mei=MICHAEL H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FUJIMURAATSUSHI en-aut-sei=FUJIMURA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=6 en-affil=UMass Chan Medical School, UMass Memorial Medical 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 Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=9 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=stemness kn-keyword=stemness en-keyword=cell cycle kn-keyword=cell cycle en-keyword=epithelial?mesenchymal transition kn-keyword=epithelial?mesenchymal transition 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=20251028 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The effect of pressure on dihedral angle between liquid Fe]S and orthopyroxene: Implication for percolative core formation in planetesimals and planetary embryos en-subtitle= kn-subtitle= en-abstract= kn-abstract=During precursor stages of planet formation, many planetesimals and planetary embryos are considered to have differentiated, forming an iron-alloy core and silicate mantle. Percolation of liquid iron-alloy in solid silicates is one of the major possible differentiation processes in these small bodies. Based on the dihedral angles between Fe-S melts and olivine, a criterion for determining whether melt can percolate through a solid, it has been reported that Fe-S melt can percolate through olivine matrices below 3?GPa in an oxidized environment. However, the dihedral angle between Fe-S melts and orthopyroxene (opx), the second most abundant mineral in the mantles of small bodies, has not yet been determined. In this study, high-pressure and high-temperature experiments were conducted under the conditions of planetesimal and planetary embryo interiors, 0.5?5.0?GPa, to determine the effect of pressure on the dihedral angle between Fe-S melts and opx. Dihedral angles tend to increase with pressure, although the pressure dependence is markedly reduced above 4?GPa. The dihedral angle is below the percolation threshold of 60 at pressures below 1.0?1.5?GPa, indicating that percolative core formation is possible in opx-rich interiors of bodies where internal pressures are lower than 1.0?1.5?GPa. The oxygen content of Fe-S melt decreases with increasing pressure. High oxygen contents in Fe-S melt reduce interfacial tension between Fe-S melt and opx, resulting in reduced dihedral angles at low pressure. Combined with previous results for dihedral angle variation of the olivine/Fe-S system, percolative core formation possibly occurs throughout bodies up to a radius of 1340?km for an olivine-dominated mantle, and up to 770?km for an opx-dominated mantle, in the case of S-rich cores segregating under relatively oxidizing conditions. For mantles of small bodies in which abundant olivine and opx coexist, the mineral with the largest volume fraction and/or smallest grain size will allow formation of interconnected mineral channels, and, therefore, the wetting property of this mineral determines the wettability of the melt, that is, controls core formation. en-copyright= kn-copyright= en-aut-name=MiuraTakumi en-aut-sei=Miura en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TerasakiHidenori en-aut-sei=Terasaki en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakakiHyu en-aut-sei=Takaki en-aut-mei=Hyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiKotaro en-aut-sei=Kobayashi en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BromileyGeoffrey David en-aut-sei=Bromiley en-aut-mei=Geoffrey David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshinoTakashi en-aut-sei=Yoshino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Earth and Space Science, Osaka University kn-affil= affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=5 en-affil=School of Geosciences, The University of Edinburgh kn-affil= affil-num=6 en-affil=Institute for Planetary Materials, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=130 cd-vols= no-issue=10 article-no= start-page=e2025JB032215 end-page= 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=Electrical Conductivity of Carbonated Hydrous Basaltic Melt: Implications for the Conductivity Anomaly Beneath the Ocean Floors en-subtitle= kn-subtitle= en-abstract= kn-abstract=We measured the electrical conductivity of CO2 and H2O-bearing basaltic melts up to 1750 K at 2 GPa, corresponding to pressure around the lithosphere-asthenosphere boundary. The electrical conductivity of the dry and hydrous samples is comparable to those reported by previous studies on the Fe-free basaltic melt. The substantial CO2 can limit the water solubility in basaltic melt at 2 GPa. Both CO2 and H2O, which cannot completely dissolve in the melt, coexist as fluid phases, resulting in reduced electrical conductivity of the basaltic melt, which has a lower water content relative to the amount of volatile components in the bulk starting system. The activation enthalpy of basaltic melt is markedly higher than those of more evolved silicate melts, especially on the H2O-poor condition, due to the more enriched alkaline earth elements. The present results suggest that an overall melt fraction of 0.1?5.3 vol% is needed to account for the high electrical conductivity anomalies (10?1.3 to 10?0.3 S/m) beneath the oceanic plate near the East Pacific Rise and Cocos plate. However, for those regions where the electrical conductivity is extremely high (?10?0.3 S/m), more than 6 wt% H2O is expected to incorporate to maintain a melt fraction that will not trigger mechanical instability. In turn, it requires a low CO2 budget or degree of carbonation within these regions. en-copyright= kn-copyright= en-aut-name=ZhaoBin en-aut-sei=Zhao en-aut-mei=Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhuJintao en-aut-sei=Zhu en-aut-mei=Jintao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HeJinze en-aut-sei=He en-aut-mei=Jinze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshinoTakashi en-aut-sei=Yoshino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=Institute for Planetary Materials, Okayama University kn-affil= en-keyword=electrical conductivity kn-keyword=electrical conductivity en-keyword=basaltic melts kn-keyword=basaltic melts en-keyword=oceanic floors kn-keyword=oceanic floors en-keyword=high pressure kn-keyword=high pressure END start-ver=1.4 cd-journal=joma no-vol=478 cd-vols= no-issue= article-no= start-page=123708 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Two Japanese families with adult-onset leukoencephalopathy caused by pathogenic variants in CST3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=CST3 (NM_000099.4) encodes cystatin C, whose C-terminal truncating variants in this gene have recently been reported to cause adult-onset leukoencephalopathy, characterized by headaches, transient neurological symptoms, and distinct imaging findings. We present four patients from two Japanese families, including one with a novel variant (c.358-2_395del). Three patients from one family developed chronic headaches around the age of 20, whereas the patient from the other family remained asymptomatic until his fifties. mRNA analysis of the patient with c.358-2_395del revealed a splicing alteration leading to an in-frame deletion (p.Lys120_Gln133del), representing the first CST3 variant that does not result in a truncated protein. These findings broaden our understanding of the clinical and genetic spectra of CST3-related leukoencephalopathy (114 words). en-copyright= kn-copyright= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=ShiomiKazutaka en-aut-sei=Shiomi en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoRyoji en-aut-sei=Goto en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuromiYumiko en-aut-sei=Kuromi en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KanaiKazuaki en-aut-sei=Kanai en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurokawaRyo en-aut-sei=Kurokawa en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=NomotoJunko en-aut-sei=Nomoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TanakaMasaki en-aut-sei=Tanaka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OmaeYosuke en-aut-sei=Omae en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KawaiYosuke en-aut-sei=Kawai en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TokunagaKatsushi en-aut-sei=Tokunaga en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 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=18 ORCID= affil-num=1 en-affil=Department of Precision Medicine 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=Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki 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, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=7 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=8 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=9 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=13 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=14 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=15 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=16 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=17 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=CST3 kn-keyword=CST3 en-keyword=Cystatin-C kn-keyword=Cystatin-C en-keyword=Leukodystrophy kn-keyword=Leukodystrophy en-keyword=Leukoencephalopathy kn-keyword=Leukoencephalopathy en-keyword=Middle cerebellar peduncle kn-keyword=Middle cerebellar peduncle en-keyword=MCP kn-keyword=MCP 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=17 cd-vols= no-issue=8 article-no= start-page=e89880 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Subacute Progression of Gait Disturbance and Consciousness Impairment Due to Communicating Hydrocephalus Associated With Vestibular Schwannoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Patients with vestibular schwannomas (VSs) present with vestibulocochlear nerve dysfunction such as vertigo and tinnitus. VSs occasionally develop communicating hydrocephalus as a complication, which is typically characterized by an insidious progression of symptoms. We report a case of an 84-year-old female patient with a VS who developed gait disturbance and consciousness impairment over a three-week period, ultimately resulting in an inability to walk and communicate. A thorough evaluation ruled out encephalitis and other differential diagnoses. Imaging studies demonstrated findings consistent with communicating hydrocephalus, and a tap test temporarily improved her consciousness disturbances. The patient underwent ventriculoperitoneal shunting and stereotactic radiosurgery (SRS), after which both consciousness and gait disturbances dramatically improved 10 days postoperatively. The subacute development of symptoms due to normal pressure hydrocephalus associated with VSs is rare. Furthermore, to the best of our knowledge, this is the first reported case of severe gait impairment and disturbance of consciousness progressing within a short period. This case highlights the importance of considering communicating hydrocephalus associated with VSs as a differential diagnosis, even in cases of subacute consciousness disturbance. We also discuss the pathophysiology of hydrocephalus in relation to cerebrospinal fluid (CSF) clearance into the extracranial space. en-copyright= kn-copyright= en-aut-name=YanoSatoka en-aut-sei=Yano en-aut-mei=Satoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KubotaAkatsuki en-aut-sei=Kubota en-aut-mei=Akatsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiMizuho en-aut-sei=Kawai en-aut-mei=Mizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YashitaDaiki en-aut-sei=Yashita en-aut-mei=Daiki 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=SatakeWataru en-aut-sei=Satake en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamadaKaoru en-aut-sei=Yamada en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShinyaYuki en-aut-sei=Shinya en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyawakiSatoru en-aut-sei=Miyawaki en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwatsuboTakeshi en-aut-sei=Iwatsubo en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine kn-affil= affil-num=2 en-affil=Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine kn-affil= affil-num=7 en-affil=Department of Neuropathology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine kn-affil= affil-num=8 en-affil=Department of Neurosurgery, The University of Tokyo Graduate School of Medicine and Faculty of Medicine kn-affil= affil-num=9 en-affil=Department of Neurosurgery, The University of Tokyo Graduate School of Medicine and Faculty of Medicine kn-affil= affil-num=10 en-affil=Department of Neuropathology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine kn-affil= affil-num=11 en-affil=Department of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine kn-affil= en-keyword=communicating hydrocephalus kn-keyword=communicating hydrocephalus en-keyword=csf dynamics kn-keyword=csf dynamics en-keyword=disorder of consciousness kn-keyword=disorder of consciousness en-keyword=ventriculoperitoneal shunting kn-keyword=ventriculoperitoneal shunting en-keyword=vestibular schwannoma kn-keyword=vestibular schwannoma END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=4 article-no= start-page=dsaf016 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250619 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reference-based chromosome-scale assembly of Japanese barley (Hordeum vulgare ssp. vulgare) cultivar Hayakiso 2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Current advances in next-generation sequencing (NGS) technology and assembling programs permit construct chromosome-level genome assemblies in various plants. In contrast to resequencing, the genome sequences provide comprehensive annotation data useful for plant genetics and breeding. Herein, we constructed a reference-based genome assembly of winter barley (H. vulgare ssp. vulgare) cv. eHayakiso 2f using long and short read NGS data and barley reference genome sequences from eMorexf. We constructed eHayakiso 2f genome sequences covering 4.3 Gbp with 55,477 genes. Comparative genomics revealed that 14,106 genes had orthologs to two barley data, wheat (A, B, and D homoeologs, respectively), and rice. From the gene ontology analysis, 2,494 orthologs against wheat and rice but not two barley contained agricultural important genes, such as eresponse to biotic and abiotic stressf and emetabolic processf. Phylogenetic analysis using 76 pangenome data indicated that eHayakiso 2f was clustered into Japanese-type genomes with unique alleles. eHayakiso 2f genome sequences showed known genes related to flowering and facilitated barley breeding through the development of various markers related to agronomically important alleles such as tolerance to various types of biotic and abiotic stress. Therefore, eHayakiso 2f genome sequences will be used for the further barley breeding. en-copyright= kn-copyright= en-aut-name=TanakaTsuyoshi en-aut-sei=Tanaka en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraguchiYuhi en-aut-sei=Haraguchi en-aut-mei=Yuhi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TodorokiTakatomo en-aut-sei=Todoroki en-aut-mei=Takatomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaishoDaisuke en-aut-sei=Saisho en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbikoTomomi en-aut-sei=Abiko en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KaiHiroomi en-aut-sei=Kai en-aut-mei=Hiroomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Bioinformatics Unit, Research Center for Advanced Analysis, National Agriculture and Food Research Organization kn-affil= affil-num=2 en-affil=Department of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research Center kn-affil= affil-num=3 en-affil=Department of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research Center kn-affil= affil-num=4 en-affil=Barley Germplasm Center, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Laboratory of Agroecology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University kn-affil= affil-num=6 en-affil=Department of Crop Production and Breeding, Fukuoka Agriculture and Forestry Research Center kn-affil= en-keyword=Hordeum vulgare kn-keyword=Hordeum vulgare en-keyword=genome sequencing kn-keyword=genome sequencing en-keyword=long-read sequencing kn-keyword=long-read sequencing END start-ver=1.4 cd-journal=joma no-vol=89 cd-vols= no-issue=11 article-no= start-page=337 end-page=343 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ti-18Nb-xAl̍\ƍޗɋyڂAlYʂ̉e en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Ti-18mass%Nb alloy with a quenched h martensitic structure exhibited a high damping capacity. However, there are issues such as lower strength than annealed + structure and decreasing damping capacity due to heating until 400 K. Therefore, in this study, to address these issues, we investigated the effect of Al addition on the constituent phases and material properties of Ti-18Nb-xAl alloys. The crystal structure was determined by examining the lattice constant and unit volume using X-ray diffraction, and optical microscopy was also performed. The material properties were investigated by Vickers hardness, Youngfs modulus, internal friction, tensile tests, and DSC measurements. Vickers hardness and tensile strength increased with increasing Al content. This is thought to be due to the combined effects of the refinement of the microstructure and solid-solution strengthening due to Al addition. The Youngfs modulus increased slightly from 0Al to 1Al, but increased significantly to 4Al. Internal friction was highest for 0Al and decreased for 4Al, whereas 7Al showed a higher value than 1Al. In the DSC heating curves, there was a decrease in the exothermic peak starting temperature and an increase in the phase-transformation heat with the addition of Al, except for 1Al. It was suggested that these changes in Ti-18Nb-xAl alloys were influenced by the structure of the quenched h phase, texture, and pseudoelasticity or phase transformation by deformation. en-copyright= kn-copyright= en-aut-name=MantaniYoshikazu en-aut-sei=Mantani en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakemotoYoshito en-aut-sei=Takemoto en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Materials Science and Engineering, National Institute of Technology (KOSEN), Suzuka College kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=ternary titanium alloy kn-keyword=ternary titanium alloy en-keyword=martensite kn-keyword=martensite en-keyword=lattice constant kn-keyword=lattice constant en-keyword=hardness kn-keyword=hardness en-keyword=Youngfs modulus kn-keyword=Youngfs modulus en-keyword=internal friction kn-keyword=internal friction en-keyword=cyclic tensile test kn-keyword=cyclic tensile test en-keyword=texture kn-keyword=texture END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e95411 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary Lacrimal Sac Diffuse Large B-cell Lymphoma Treated With Local Radiotherapy Alone: A Case With No Relapse After 21 Years of Follow-Up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary lacrimal sac lymphoma is rare and diagnosed as diffuse large B-cell lymphoma in a predominant histopathological type. Systemic chemotherapy would be the standard of care, but local radiotherapy may be a treatment option toward a localized lesion. The present patient is a 54-year-old otherwise healthy woman with a right lacrimal sac mass, which was proven by excisional biopsy to be diffuse large B-cell lymphoma. Since she did not have any other systemic lesions on gallium scintigraphy and neck-to-abdominal computed tomography scans, which were the standard procedure at that time, she underwent local radiotherapy at 40 Gy. Two years later, at the age of 56 years, she developed radiation retinopathy with macular edema in the right eye and had spotty laser photocoagulation in the nasal half of the fundus. At the age of 57 years, she developed radiation cataract and underwent cataract surgery with intraocular lens implantation in the right eye. At the age of 58 years, the macular edema in the right eye became worse and remained active, resulting in poor visual acuity of 0.1. She thus underwent 25-gauge vitrectomy in the right eye to peel off the adhering posterior vitreous surface, together with the internal limiting membrane, as the standard procedure at that time. The visual acuity in the right eye was elevated to 0.6. She maintained the visual acuity afterward and had no relapse of lymphoma in 21 years from the diagnosis of primary right lacrimal sac diffuse large B-cell lymphoma. Local radiotherapy would still be a treatment option for localized lymphoma lesions such as primary lacrimal sac lymphoma. 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=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakemotoMitsuhiro en-aut-sei=Takemoto en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Radiotherapy, Himeji Red Cross Hospital kn-affil= en-keyword=diffuse large b-cell lymphoma kn-keyword=diffuse large b-cell lymphoma en-keyword=excisional biopsy kn-keyword=excisional biopsy en-keyword=lacrimal sac kn-keyword=lacrimal sac en-keyword=laser photocoagulation kn-keyword=laser photocoagulation en-keyword=macular edema kn-keyword=macular edema en-keyword=pathology kn-keyword=pathology en-keyword=radiation cataract kn-keyword=radiation cataract en-keyword=radiation retinopathy kn-keyword=radiation retinopathy en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=vitrectomy kn-keyword=vitrectomy END start-ver=1.4 cd-journal=joma no-vol=94 cd-vols= no-issue=11 article-no= start-page=113801 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Magnetically Enhanced Thermoelectric Effect Driven by Martensitic Transformation in the Weak Itinerant Ferromagnet Co2NbSn en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the magnetic and thermoelectric properties of the full Heusler alloy Co2NbSn, which exhibits a martensitic transformation at 240 K. Magnetization measurements reveal weak itinerant ferromagnetism in the martensitic phase, which is well described by Takahashifs spin fluctuation theory. The characteristic spin fluctuation parameters were estimated to be T0 = 1.0 ~ 103 K and TA = 7.2 ~ 103 K. Seebeck coefficient measurements under magnetic fields up to 9 T show complex temperature and field dependence, which we decomposed into electron diffusion, spin fluctuation drag, and magnon drag components. A significant magnon-drag contribution was identified in both austenite and martensitic phases. Remarkably, this contribution is strongly enhanced in the martensitic phase compared to the austenite phase, despite a smaller magnetic moment. These findings provide evidence for robust low-energy spin excitations and highlight the potential of martensitic transformation in enhancing the thermoelectric performance of itinerant ferromagnetic alloys. en-copyright= kn-copyright= en-aut-name=KiharaTakumi en-aut-sei=Kihara en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=XuXiao en-aut-sei=Xu en-aut-mei=Xiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OgiYuki en-aut-sei=Ogi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AdachiYoshiya en-aut-sei=Adachi en-aut-mei=Yoshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RoyTufan en-aut-sei=Roy en-aut-mei=Tufan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsuuraRyuji en-aut-sei=Matsuura en-aut-mei=Ryuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanomataTakeshi en-aut-sei=Kanomata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Materials Science, Tohoku University kn-affil= affil-num=3 en-affil=Graduate School of Science and Engineering, Yamagata University kn-affil= affil-num=4 en-affil=Graduate School of Science and Engineering, Yamagata University kn-affil= affil-num=5 en-affil=Center for Science and Innovation in Spintronics (CSIS), Core Research Cluster (CRC), Tohoku University kn-affil= affil-num=6 en-affil=Faculty of Engineering, Tohoku Gakuin University kn-affil= affil-num=7 en-affil=Research Institute for Engineering and Technology, Tohoku Gakuin 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=2025 dt-pub=20251014 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative analysis of interactions between five strains of Pseudomonas syringae pv. tabaci and Nicotiana benthamiana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pseudomonas syringae pv. tabaci 6605 (Pta 6605), the agent of wildfire disease in tobacco, has been used as a model strain for elucidating the virulence mechanisms of Pta. However, the host genes involved in resistance or susceptibility to Pta remain largely unknown. Nicotiana benthamiana is a model plant species in the Solanaceae family and is useful in functional analyses of genes. We herein compared five Pta strains (6605, 6823, 7372, 7375, and 7380) in terms of their phenotypes on medium and interactions with N. benthamiana. Pta 6605 and Pta 6823 showed more active proliferation than the other strains in a high cell density culture. Moreover, Pta 6605 exhibited markedly higher swarming motility than the other strains. In inoculated leaves of N. benthamiana, Pta 6605 and Pta 6823 caused more severe disease symptoms and proliferated to a higher cell density than the other strains. However, Pta 6823 as well as Pta 7372 and Pta 7380 induced the high accumulation of salicylic acid (SA). Moreover, the inoculations of Pta 6823 and Pta 7372 resulted in the upregulation of ethylene biosynthesis genes. On the other hand, Pta 6605 induced neither SA accumulation nor the expression of ethylene biosynthesis genes, and suppressed the expression of jasmonate biosynthesis genes. Moreover, chlorosis was clearly induced in the upper uninoculated leaves of Pta 6605-infected plants. These results suggest that Pta 6605 escapes from or suppresses plant immune systems and, thus, is the most virulent on N. benthamiana among the five strains tested. en-copyright= kn-copyright= en-aut-name=NakaoYuna en-aut-sei=Nakao en-aut-mei=Yuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsaiShuta en-aut-sei=Asai en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=KatouShinpei en-aut-sei=Katou en-aut-mei=Shinpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Science and Technology, Shinshu University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Science and Technology, Shinshu University kn-affil= en-keyword=Chlorosis kn-keyword=Chlorosis en-keyword=Nicotiana benthamiana kn-keyword=Nicotiana benthamiana en-keyword=Phytohormones kn-keyword=Phytohormones en-keyword=Pseudomonas syringae pv. tabaci kn-keyword=Pseudomonas syringae pv. tabaci END start-ver=1.4 cd-journal=joma no-vol=150 cd-vols= no-issue= article-no= start-page=110530 end-page= 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=Surrogate-assisted motion planning and layout design of robotic cellular manufacturing systems en-subtitle= kn-subtitle= en-abstract= kn-abstract=A surrogate-assisted multi-objective evolutionary algorithm is proposed for simultaneous optimization of robot motion planning and layout design in robotic cellular manufacturing systems. A sequence-pair is used to represent the layout of components in a robotic cell to avoid overlapping in the evolutionary computation. The robot motion planning with Rapidly exploring Random Trees Star (RRT*) is applied to compute the total operation time of a robot arm for each layout. Non-dominated Sorting Genetic Algorithm II (NSGA-II) is used to minimize the total required layout area and the operation time for a robot arm. The proposed surrogate model can estimate the robotfs operation time with 98% of accuracy without explicit computations of the motion planning algorithm. The experimental results with a physical 6 Degree of Freedom (DOF) manipulator show that the total computation time is approximately 1/400, significantly shorter than the conventional methods. en-copyright= kn-copyright= en-aut-name=KawabeTomoya en-aut-sei=Kawabe en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiTatsushi en-aut-sei=Nishi en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiuZiang en-aut-sei=Liu en-aut-mei=Ziang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraTomofumi en-aut-sei=Fujiwara en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life and Natural Science and Technology, Okayama University kn-affil= en-keyword=Robotics kn-keyword=Robotics en-keyword=Cellular manufacturing kn-keyword=Cellular manufacturing en-keyword=Layout design kn-keyword=Layout design en-keyword=Sequence-pair kn-keyword=Sequence-pair en-keyword=Motion planning kn-keyword=Motion planning en-keyword=Surrogate optimization kn-keyword=Surrogate optimization en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Artificial intelligence kn-keyword=Artificial intelligence END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=20 article-no= start-page=10072 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251016 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurofibromin Encoded by the Neurofibromatosis Type 1 (NF1) Gene Promotes the Membrane Translocation of SPRED2, Thereby Inhibiting the ERK Pathway in Breast Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neurofibromin (NF) inhibits the RAS/RAF/ERK pathway through its interaction with SPRED1 (Sprouty-related EVH1 domain-containing protein 1). Here, we investigated the functional relationship between NF and SPRED2 in breast cancer (BC). Human BC cell lines were transfected to downregulate or overexpress NF and SPRED2 and subsequently subjected to functional assays. Protein and mRNA levels were analyzed by Western blotting and RT-qPCR, respectively. Protein?protein interactions were examined by immunoprecipitation. Database analyses and immunohistochemistry (IHC) of BC tissues were performed to validate the in vitro findings. Downregulating NF or SPRED2 expression in BC cells enhanced cell proliferation, migration and invasion accompanied by RAF/ERK activation, whereas overexpression produced opposite effects. NF formed a protein complex with SPRED2 and facilitated its translocation to the plasma membrane. By IHC, SPRED2 membrane localization was absent in NF-negative luminal A and triple-negative BC (TNBC) but present in a subset of luminal A BC. By database analyses, both NF1 and SPRED2 mRNA levels were reduced in BC tissues, and luminal A BC patients with high expression of both NF1 and SPRED2 mRNA exhibited improved relapse-free survival. These results suggest a critical role for the NF?SPRED2 axis in BC progression and highlight it as a potential therapeutic target. en-copyright= kn-copyright= en-aut-name=Su PwintNang Thee en-aut-sei=Su Pwint en-aut-mei=Nang Thee kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiChunning en-aut-sei=Li en-aut-mei=Chunning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong 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=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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 Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=SPRED2 kn-keyword=SPRED2 en-keyword=neurofibromatosis type 1 kn-keyword=neurofibromatosis type 1 en-keyword=neurofibromin kn-keyword=neurofibromin en-keyword=RAS/RAF/ERK kn-keyword=RAS/RAF/ERK END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=20 article-no= start-page=3287 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Neoadjuvant Chemotherapy with Gemcitabine Plus S-1 in Patients with Resectable Pancreatic Ductal Adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Although neoadjuvant chemotherapy (NAC) is not universally recommended for resectable pancreatic ductal adenocarcinoma (PDAC), NAC with gemcitabine plus S-1 (NAC-GS) has become a commonly used regimen for resectable PDAC in Japan. Furthermore, the impact of achieving textbook outcomes (TO) in patients receiving NAC-GS remains unclear. Methods: This retrospective study included 265 patients who were diagnosed with resectable PDAC at our institution between January 2009 and December 2023. Patients were categorized into two groups: the NAC-GS group (n = 81; 2019?2023) and the upfront surgery (UFS) group (n = 164; 2009?2018). After comparing the clinical outcomes between groups, multivariate analyses for survival were performed. Additionally, outcomes stratified by the achievement of the modified TO were analyzed in the NAC-GS group. Results: The completion rate of NAC-GS was 90.1%. Patients in the NAC-GS group exhibited significantly longer survival than those in the UFS group (2-year recurrence-free survival: 61.4% vs. 37.9%, p < 0.01; 2-year overall survival: 83.2% vs. 61.2%, p < 0.01). Multivariate analyses identified lymph node metastasis, NAC-GS induction, and completion of adjuvant chemotherapy as factors significantly associated with improved survival. Moreover, among patients who received NAC-GS, those who achieved modified TO demonstrated significantly longer survival than those who did not. Conclusions: This study demonstrated the clinical efficacy of NAC-GS in patients with resectable PDAC. Induction of NAC-GS was significantly associated with improved long-term outcomes. In multidisciplinary treatment strategies for PDAC, achieving a modified TO may lead to improved survival of patients undergoing NAC-GS. en-copyright= kn-copyright= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 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=6 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=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 Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, 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 Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=neoadjuvant chemotherapy kn-keyword=neoadjuvant chemotherapy en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=resectable kn-keyword=resectable en-keyword=textbook outcome kn-keyword=textbook outcome 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=20251017 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ATPase copper transporting beta contributes to cisplatin resistance as a regulatory factor of extracellular vesicles in head and neck squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cisplatin (CDDP) resistance remains a major clinical challenge in the treatment of head and neck squamous cell carcinoma (HNSC). Our group identified ATPase copper transporting beta (ATP7B) as a mediator of CDDP resistance through its role in drug efflux and small extracellular vesicle (sEV) secretion. Herein, we uncovered a novel mechanism by which ATP7B regulates sEV dynamics and the intercellular transmission of CDDP resistance. Using transcriptomic analyses of HNSC datasets, we demonstrate that ATP7B expression correlates with endocytosis- and epithelial-mesenchymal transition (EMT)-related gene sets and with elevated levels of EV-associated proteins. CDDP-resistant HNSC cells exhibited upregulated ATP7B, Rab5/Rab7, and preferentially secreted HSP90- and EpCAM-rich sEVs. These sEVs were leading to increased ATP7B expression and reduced CDDP sensitivity in recipient cells. A pharmacological inhibition of sEV biogenesis with GW4869 suppressed ATP7B and Atox1 expressions, inhibited late endosome maturation, and significantly enhanced CDDP-induced apoptosis in HNSC cells. In vivo, GW4869 reduced the sEV protein content and ATP7B expression in xenograft tumors. These findings establish that ATP7B is a critical modulator of sEV cargo and resistance propagation. Our results highlight a previously unrecognized ATP7B?sEV axis driving chemoresistance and identify sEV inhibition as a promising strategy to overcome therapeutic failure in HNSC. en-copyright= kn-copyright= en-aut-name=OgawaTatsuo en-aut-sei=Ogawa en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RyumonShoji en-aut-sei=Ryumon en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKohei en-aut-sei=Sato en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UmemoriKoki en-aut-sei=Umemori en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaKunihiro en-aut-sei=Yoshida en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkuiTatsuo en-aut-sei=Okui en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Momen-HeraviFatemeh en-aut-sei=Momen-Heravi en-aut-mei=Fatemeh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=11 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Orofacial Sciences, School of Dentistry, University of California San Francisco kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=5 article-no= start-page=234 end-page=249 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=Biochar-amended Sediment Microbial Fuel Cells for Water Quality Improvement in Intensive and Extensive Pond Drainages in Central Vietnam en-subtitle= kn-subtitle= en-abstract= kn-abstract=The use of nutrient-rich feed in shrimp farming in Central Vietnam has led to high nitrogen (N) and phosphorus (P) contents in the pond sediment. The objectives of the study were to assess the effectiveness of biochar-sediment microbial fuel cells (BC-SMFCs) in suppressing P and N release from two types of sediment in intensive (Int) and extensive (Ext) pond drainages in Central Vietnam. Single chamber SMFCs were set up and operated under open or closed-circuit (no SMFC or SMFC) conditions. Coconut shell biochar (BC) was amended to sediments at 1%. For Int-sediment, total phosphorus (TP) release was reduced by no BC-SMFCs through co-precipitation with Fe. On the other hand, BC-SMFCs did not suppress TP release because P was released from BC and organic matter decomposition was enhanced in the sediment. Application of BC enhanced organic N mineralization in the sediment. Nitrification and denitrification occurred in the overlying water, reducing mineral N concentrations. For Ext-sediment, BC addition and SMFC conditions did not affect TP and total nitrogen (TN) release because of low initial organic matter content, and less reductive condition. Our study suggested that the effect of SMFCs was masked by BC which released more P from Int-sediment to the water. en-copyright= kn-copyright= en-aut-name=NguyenUyen Tu en-aut-sei=Nguyen en-aut-mei=Uyen Tu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaMorihiro en-aut-sei=Maeda en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SomuraHiroaki en-aut-sei=Somura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaharaNozomi en-aut-sei=Nakahara en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PereraGamamada Liyanage Erandi Priyangika en-aut-sei=Perera en-aut-mei=Gamamada Liyanage Erandi Priyangika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoChiyu en-aut-sei=Nakano en-aut-mei=Chiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LeHuu Tien en-aut-sei=Le en-aut-mei=Huu Tien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Comprehensive Technical Solutions, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Education, Science and Technology Quang Tri Branch, Hue University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=biochar kn-keyword=biochar en-keyword=Central Vietnam kn-keyword=Central Vietnam en-keyword=electricity generation kn-keyword=electricity generation en-keyword=redox potential kn-keyword=redox potential en-keyword=shrimp farming kn-keyword=shrimp farming END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=10 article-no= start-page=105028 end-page= 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=Evaluating the effects of electrolytes on the interaction forces between alumina surfaces in polyacrylic acid solutions using atomic force microscopy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Evaluation and control of ceramic slurry at the microscopic level are critical to ensure consistent quality in manufactured ceramics. Notably, metal ions such as Mg2+ and Al3+ are common in ceramic slurries and significantly influence the stability of particle. This study applied atomic force microscopy to investigate the interaction forces between alumina particle surfaces in the presence of different concentrations of three metal ions and polyacrylic acid (PAA), a widely used dispersant.
The attractive forces observed at low PAA concentrations were attributed to polymer bridging between alumina surfaces, whereas the repulsive forces observed at high PAA concentrations were attributed to the domination of steric repulsion between adsorbed PAA molecules. The presence of multivalent metal ions, such as Mg2+ and Al3+, modulated these interactions; an increasing ion valence induced a transition from repulsive to attractive force, primarily owing to electrostatic screening, which caused conformational collapse of the PAA chains and diminished the range of steric repulsion. Similarly, increasing the concentration of these metal ions decreased the range of repulsive forces, eventually resulting in a net attraction driven by the same electrostatic and polymer conformation mechanisms. Notably, the addition of 0.1 M AlCl3 produced an anomalous long-range attraction between surfaces that could not be explained by conventional mechanisms, such as polymer bridging or electrostatic interactions between charge domains. en-copyright= kn-copyright= en-aut-name=KishimotoNaoto en-aut-sei=Kishimoto en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KajiRyota en-aut-sei=Kaji en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchiyaKatsumi en-aut-sei=Tsuchiya en-aut-mei=Katsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImamuraKoreyoshi en-aut-sei=Imamura en-aut-mei=Koreyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshidaNaoyuki en-aut-sei=Ishida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Science and Engineering, Doshisha University kn-affil= affil-num=3 en-affil=Faculty of Science and Engineering, Doshisha 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 and Engineering, Doshisha University kn-affil= en-keyword=Interaction force kn-keyword=Interaction force en-keyword=Alumina surface kn-keyword=Alumina surface en-keyword=Anionic polyelectrolyte kn-keyword=Anionic polyelectrolyte en-keyword=Coexisting electrolyte kn-keyword=Coexisting electrolyte en-keyword=Atomic force microscopy kn-keyword=Atomic force microscopy END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=3 article-no= start-page=ME25019 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=Role of Formate Chemoreceptor in Pseudomonas syringae pv. tabaci 6605 in Tobacco Infection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chemotaxis is essential for infection by plant pathogenic bacteria. The causal agent of tobacco wildfire disease, Pseudomonas syringae pv. tabaci 6605 (Pta6605), is known to cause severe leaf disease and is highly motile. The requirement of chemotaxis for infection has been demonstrated through the inoculation of mutant strains lacking chemotaxis sensory component proteins. Pta6605 possesses 54 genes that encode chemoreceptors (known as methyl-accepting chemotaxis proteins, MCPs). Chemoreceptors are classified into several groups based on the type and localization of ligand-binding domains (LBD). Cache LBD-type chemoreceptors have been reported to recognize formate in several bacterial species. In the present study, we identified Cache_3 Cache_2 LBD-type Mcp26 encoded by Pta6605_RS00335 as a chemoreceptor for formate using a quantitative capillary assay, and named it McpF. Although the deletion mutant of mcpF (mcpF) retained attraction to 1% yeast extract, its chemotactic response to formate was markedly reduced. Swimming and swarming motilities were also impaired in the mutant. To investigate the effects of McpF on bacterial virulence, we conducted inoculations on tobacco plants using several methods. The mcpF mutant exhibited weaker virulence in flood and spray assays than wild-type and complemented strains, highlighting not only the involvement of McpF in formate recognition, but also its critical role in leaf entry during the early stages of infection. en-copyright= kn-copyright= en-aut-name=NguyenPhuoc Quy Thang en-aut-sei=Nguyen en-aut-mei=Phuoc Quy Thang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeYuta en-aut-sei=Watanabe en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 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=6 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=7 ORCID= affil-num=1 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=The Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=chemoreceptor kn-keyword=chemoreceptor en-keyword=formate kn-keyword=formate en-keyword=mcpF kn-keyword=mcpF en-keyword=Pseudomonas syringae kn-keyword=Pseudomonas syringae en-keyword=virulence kn-keyword=virulence END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=9 article-no= start-page=251152 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=On weapons allometry and the form of sexual selection en-subtitle= kn-subtitle= en-abstract= kn-abstract=The study of trait scaling with body size (allometry) has a long history, and it has been argued that positive static allometry is an indicator of directional sexual selection. However, a range of allometries exists for sexually selected traits, and modelling shows this variation can be generated by altering the form of selection (fitness functions) on the trait and/or body size. Interestingly, in all models, positive allometry appears to emerge only when there is directional selection on trait size. Here, we report on a sexually selected trait that shows strong positive static allometry and yet appears to be under stabilizing selection. This surprising finding suggests the evolution of trait scaling is even more nuanced than currently appreciated. en-copyright= kn-copyright= en-aut-name=ShinoharaHironori en-aut-sei=Shinohara en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SharmaManmohan D. en-aut-sei=Sharma en-aut-mei=Manmohan D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PennellTanya M. en-aut-sei=Pennell en-aut-mei=Tanya M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkadaKensuke en-aut-sei=Okada en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoskenDavid J. en-aut-sei=Hosken en-aut-mei=David J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Center for Ecology and Conservation, University of Exeter, Cornwall Campus kn-affil= affil-num=2 en-affil=Center for Ecology and Conservation, University of Exeter, Cornwall Campus kn-affil= affil-num=3 en-affil=Center for Ecology and Conservation, University of Exeter, Cornwall Campus kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Center for Ecology and Conservation, University of Exeter, Cornwall Campus kn-affil= en-keyword=inbreeding kn-keyword=inbreeding en-keyword=selection kn-keyword=selection en-keyword=beetle kn-keyword=beetle en-keyword=Gnatocerus kn-keyword=Gnatocerus END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue=3 article-no= start-page=215 end-page=227 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=Root-exuded sugars as drivers of rhizosphere microbiome assembly en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sugars in root exudates play a pivotal role in shaping plant-microbe interactions in the rhizosphere, serving as carbon sources and signaling molecules that orchestrate microbial behavior, community structure, and plant resilience. Recent research has shed light on the dynamics of sugar levels in root exudates, the factors that influence their secretion, and the mechanisms by which these sugars drive microbial colonization and community assembly in the rhizosphere. Microbial communities, in turn, contribute to plant physiological changes that enhance growth and stress tolerance. While well-studied sugars such as glucose, sucrose, and fructose are known to promote chemotaxis, motility, and biofilm formation, emerging evidence suggests that less-studied sugars like arabinose and trehalose may also play significant roles in microbial interactions and stress resilience. Key challenges remain, including the accurate measurement of labile sugars that are rapidly metabolized by microbes, and the elucidation of genetic mechanisms underlying rhizosphere metabolic interactions in both host plants and microbes. Addressing these challenges will advance our understanding of sugar-mediated interactions and inform the development of sustainable agricultural innovations. en-copyright= kn-copyright= en-aut-name=HemeldaNiarsi Merry en-aut-sei=Hemelda en-aut-mei=Niarsi Merry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= affil-num=1 en-affil=Department of Biology, Faculty of Mathematics and Natural Sciences, University of Indonesia kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=carbon sources kn-keyword=carbon sources en-keyword=plant-derived sugars kn-keyword=plant-derived sugars en-keyword=plant-microbe interactions kn-keyword=plant-microbe interactions en-keyword=rhizosphere kn-keyword=rhizosphere en-keyword=root exudate kn-keyword=root exudate END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=1 article-no= start-page=46 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251009 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Highly efficient transgenesis mediated by Tip100 transposon system in medaka en-subtitle= kn-subtitle= en-abstract= kn-abstract=Transgenesis mediated by transposon is an effective approach for introducing exogenous DNA into the nuclear genome and establishing stable transgenic strains that efficiently express genetic tools. Although the DNA transposon Tol2 is widely used for transgenesis in zebrafish, its endogenous transpositional activity can lead to unintended transgene mobilization, making it unsuitable for transgenesis in medaka (Oryzias latipes). Here, we demonstrated that the DNA transposon Tip100, originally identified in the common morning glory (Ipomoea purpurea), an ornamental plant, can serve as a useful tool for transgenesis in Japanese medaka. The GFP transgene cassette, when co-injected with Tip100 transposase mRNA, was expressed in significantly higher number of somatic cells in the injected fish. Furthermore, a transgene flanked by truncated recognition sequences (100 bp each) exhibited expression levels comparable to those of the original vector containing the full 2.2 kb recognition sequence. Injection of a transgene driven by a germline-specific promoter revealed that fish injected with Tip100 mRNA exhibited a significantly higher germline transmission rate (42/68; 62.7%) compared to those injected without the mRNA (13/62; 21.0%). We successfully established transgenic strains by outcrossing injected founders with GFP-positive germ cells (7/7; 100%) and demonstrated that the transgenes were randomly integrated into the medaka genome, generating 8-bp duplications at the insertional sites?an insertional signature of the hAT superfamily of transposons. Our findings indicate that the Tip100 system is a promising tool for generating stable transgenic strains that express various genetic tools in medaka and potentially other fish species. en-copyright= kn-copyright= en-aut-name=TanakaYoshitaka en-aut-sei=Tanaka en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SekiTakahide en-aut-sei=Seki en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HoshinoAtsushi en-aut-sei=Hoshino en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Ushimado Marine Institute (UMI), Okayama University kn-affil= affil-num=2 en-affil=Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=3 en-affil=National Institute for Basic Biology kn-affil= affil-num=4 en-affil=Ushimado Marine Institute (UMI), Okayama University kn-affil= en-keyword=Fish kn-keyword=Fish en-keyword=Medaka kn-keyword=Medaka en-keyword=Morning glory kn-keyword=Morning glory en-keyword=Transgenic kn-keyword=Transgenic en-keyword=Transposon kn-keyword=Transposon END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=468 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The safety and efficacy of finasteride for transgender men with androgenetic alopecia: a case series en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Testosterone replacement therapy is commonly used in transgender men for masculinization. One of the most common adverse effects of testosterone replacement therapy is androgenetic alopecia. In Japan, finasteride is approved exclusively for cisgender men and is not indicated for transgender men. The aim of this clinical trial was to evaluate the safety and efficacy of finasteride in transgender men with androgenetic alopecia.
Case presentation This study included three transgender men (assigned female at birth, identifying as male), aged 44, 43, and 29 years. All participants were of Asian ethnicity. A clinical trial was conducted from October 2021 to December 2023. Transgender men aged 20?60 years who had not undergone hysterectomy, were undergoing testosterone replacement therapy, and who had been diagnosed with stage???II androgenetic alopecia on the basis of the Norwood?Hamilton scale were recruited. The participants initiated treatment with 0.2 mg of finasteride per day for 3 months (phase 1). If no adverse events above grade 2 occurred, the dose was increased to 1.0 mg per day for an additional 3 months (phase 2). The primary endpoints were the incidence of treatment-related adverse events at 1 week, 1 month, and 3 months, as well as the rate of participants continuing treatment at 3 months. None of the patients experienced serious adverse events at 3 months, and all the patients extended their treatment to a total of 6 months. Improvements of at least one stage on the N?H scale were observed, but two participants experienced resumption of menstruation.
Conclusion Finasteride appears to be a safe and effective treatment for androgenetic alopecia in transgender men undergoing testosterone replacement therapy. However, its potential for reducing some of the effects of testosterone replacement therapy warrants further investigation. Trial registration: jRCT, jRCTs061210040, registered 7 October 2021, https://jrct.mhlw.go.jp/latest-detail/jRCTs061210040. en-copyright= kn-copyright= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoYuko en-aut-sei=Matsumoto en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakoTomoko en-aut-sei=Sako en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriwakeTakatoshi en-aut-sei=Moriwake en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriiSatoshi en-aut-sei=Horii en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 ORCID= affil-num=1 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=5 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Center for Innovative Clinical Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Finasteride kn-keyword=Finasteride en-keyword=Dihydrotestosterone kn-keyword=Dihydrotestosterone en-keyword=Transgender men kn-keyword=Transgender men en-keyword= Androgenetic alopecia kn-keyword= Androgenetic alopecia en-keyword=Resumption of menstruation kn-keyword=Resumption of menstruation 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=79 cd-vols= no-issue=5 article-no= start-page=381 end-page=385 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=Immunoglobulin G4-related Disease Mimicking Portal Vein Tumor Thrombus en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report the case of a 72-year-old Japanese man with an incidental portal vein mass that was surgically resected and diagnosed as immunoglobulin G4 (IgG4)-related disease. The mass was discovered during an atrial fibrillation examination. The patient had a history of gastric cancer and was also diagnosed with rectal cancer, raising concerns about metastasis. Due to technical challenges, a biopsy was not feasible. Imaging findings suggested portal vein tumor thrombosis, complicating the diagnosis. This case highlights a rare presentation of IgG4-related disease mimicking portal vein tumor thrombus. en-copyright= kn-copyright= en-aut-name=SakuraiAtsunobu en-aut-sei=Sakurai en-aut-mei=Atsunobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YabukiTakayuki en-aut-sei=Yabuki en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AokiHideki en-aut-sei=Aoki en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IsekiAkiko en-aut-sei=Iseki en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Radiology, NHO Iwakuni Clinical Center kn-affil= affil-num=2 en-affil=Department of Radiology, NHO Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, NHO Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Pathology, NHO Iwakuni Clinical Center kn-affil= en-keyword=immunoglobulin G4-related disease kn-keyword=immunoglobulin G4-related disease en-keyword=inflammatory pseudotumor kn-keyword=inflammatory pseudotumor en-keyword=mass kn-keyword=mass en-keyword=portal vein kn-keyword=portal vein en-keyword=pericarditis kn-keyword=pericarditis END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=369 end-page=379 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=Blood Pressure and Heart Rate Patterns Identified by Unsupervised Machine Learning and Their Associations with Subclinical Cerebral and Renal Damage in a Japanese Community: The Masuda Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=We applied unsupervised machine learning to analyze blood pressure (BP) and resting heart rate (HR) patterns measured during a 1-year period to assess their cross-sectional relationships with subclinical cerebral and renal target damage. Dimension reduction via uniform manifold approximation and projection, followed by K-means++ clustering, was used to categorize 362 community-dwelling participants (mean age, 56.2 years; 54.9% women) into three groups: Low BP and Low HR (Lo-BP/Lo-HR), High BP and High HR (Hi-BP/Hi-HR), and Low BP and High HR (Lo-BP/Hi-HR). Cerebral vessel lesions were defined as the presence of at least one of the following magnetic resonance imaging findings: lacunar infarcts, white matter hyperintensities, cerebral microbleeds, or intracranial artery stenosis. A high urinary albumin-to-creatinine ratio (UACR) was defined as the top 10% (? 12 mg/g) of the mean value from ?2 measurements. Poisson regression with robust error variance, adjusted for demographics, lifestyle, and medical history, showed that the Hi-BP/Hi-HR group had relative risks of 3.62 (95% confidence interval, 1.75-7.46) for cerebral vessel lesions and 3.58 (1.33-9.67) for high UACR, and the Lo-BP/Hi-HR group had a relative risk of 3.09 (1.12-8.57) for high UACR, compared with the Lo-BP/Lo-HR group. These findings demonstrate the utility of an unsupervised, data-driven approach for identifying physiological patterns associated with subclinical target organ damage. en-copyright= kn-copyright= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinutaMinako en-aut-sei=Kinuta en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MunetomoSosuke en-aut-sei=Munetomo en-aut-mei=Sosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukudaMari en-aut-sei=Fukuda en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KojimaKatsuhide en-aut-sei=Kojima en-aut-mei=Katsuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniguchiKaori en-aut-sei=Taniguchi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakahataNoriko en-aut-sei=Nakahata en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KandaHideyuki en-aut-sei=Kanda en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine kn-affil= affil-num=7 en-affil=Department of Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition kn-affil= affil-num=8 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=blood pressure kn-keyword=blood pressure en-keyword=heart rate kn-keyword=heart rate en-keyword=subclinical disease kn-keyword=subclinical disease en-keyword=uniform manifold approximation and projection kn-keyword=uniform manifold approximation and projection en-keyword=unsupervised machine learning kn-keyword=unsupervised machine learning END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=353 end-page=358 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=Comparison of Extraocular Muscles in Patients with Exotropia and Healthy Participants Using Anterior Segment Optical Coherence Tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=To analyze and characterize the medial and lateral rectus muscles in patients with exotropia using anterior segment optical coherence tomography (AS-OCT). This study included 24 patients with exotropia (48 eyes) and 25 healthy individuals (50 eyes). Anterior segment optical coherence tomography was used to construct the en face images. The anterior chamber angle to the extraocular muscle insertion distance, muscle width, and muscle fiber angle from the muscle insertion sites were compared between the exotropia and the control groups. The correlation between these parameters and age or angle of deviation was evaluated. The mean ages were 13.2}4.1 years for the exotropia group and 17.6}7.2 years for the control group. The lateral rectus angle was significantly more inwardly rotated in the exotropia group than in the control group (1.6}6.3, ?1.4}4.0, p=0.014). With increasing angle of deviation, the width of the lateral rectus increased (p=0.002). Our results indicate that the lateral rectus angle is significantly more inwardly rotated in patients with exotropia. These findings should contribute to a deeper understanding of the extraocular muscles in patients with this condition. en-copyright= kn-copyright= en-aut-name=ChiharaYuki en-aut-sei=Chihara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamasakiIchiro en-aut-sei=Hamasaki en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShibataKiyo en-aut-sei=Shibata en-aut-mei=Kiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorisawaShin en-aut-sei=Morisawa en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KonoReika en-aut-sei=Kono en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KanenagaKeisuke en-aut-sei=Kanenaga en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=exotropia kn-keyword=exotropia en-keyword=AS-OCT kn-keyword=AS-OCT en-keyword=anterior chamber angle to extraocular muscle insertion distance kn-keyword=anterior chamber angle to extraocular muscle insertion distance en-keyword=muscle width kn-keyword=muscle width en-keyword=muscle fiber angle kn-keyword=muscle fiber angle END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=345 end-page=352 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=Inhibition of Air-Exposure Stress?Induced Autolysis in Clostridium perfringens by Zn2+ en-subtitle= kn-subtitle= en-abstract= kn-abstract=Clostridium perfringens is a pathogenic anaerobe that causes gas gangrene and food poisoning. Although autolysin-mediated reorganization of the bacterial cell wall is crucial for cell division, excessive autolysin activity induced by stressors can lead to cell lysis. In C. perfringens, air exposure is a significant stressor that causes cell lysis, and Acp (N-acetylglucosaminidase) is known to be a major autolysin. To further facilitate C. perfringens research, a technology to prevent air-induced cell lysis must be developed. This study investigated the role of Acp in air-induced autolysis and explored potential inhibitors that would prevent cell lysis during experimental procedures. Morphological analyses confirmed that Acp functions as an autolysin in C. perfringens, as acpdeficient strains exhibited filamentous growth. The mutants exhibited negligible autolysis under air-exposure stress, confirming the involvement of Acp in the autolytic process. We also evaluated the effects of various divalent cations on Acp activity in vitro and identified Zn2+ as a potent inhibitor. Brief treatment with a Zn2+- containing buffer induced dose-dependent cell elongation and autolysis inhibition in C. perfringens. These findings demonstrate that simple Zn2+ treatment before experiments stabilizes C. perfringens cells, reducing autolysis under aerobic conditions and facilitating various biological studies, except morphological analyses. en-copyright= kn-copyright= en-aut-name=MatsunagaNozomu en-aut-sei=Matsunaga en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EgusaSeira en-aut-sei=Egusa en-aut-mei=Seira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AonoRiyo en-aut-sei=Aono en-aut-mei=Riyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TamaiEiji en-aut-sei=Tamai en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HitusmotoYasuo en-aut-sei=Hitusmoto en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaSeiichi en-aut-sei=Katayama en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=2 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=3 en-affil=Department of Medical Technology, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=4 en-affil=Department of Infectious Disease, College of Pharmaceutical Science, Matsuyama University kn-affil= affil-num=5 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=6 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= en-keyword=Clostridium perfringens kn-keyword=Clostridium perfringens en-keyword=autolysin kn-keyword=autolysin en-keyword=zinc kn-keyword=zinc en-keyword=air-exposure autolysis kn-keyword=air-exposure autolysis END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=329 end-page=337 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=Current Status of Extracorporeal Membrane Oxygenation as a Treatment Strategy for Primary Graft Dysfunction after Lung Transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary graft dysfunction (PGD) is one of the major risk factors affecting patientsf short- and long-term survival after lung transplantation. No particular management strategy has been established for PGD; supportive care is the mainstay of PGD treatment. When a supportive strategy fails, the patient may require the introduction of extracorporeal membrane oxygenation (ECMO) as the last-resort measure for severe PGD. A variety of study of ECMO as a PGD treatment was reported and the management of PGD patients developed so far. Early recognition of a patientfs need for ECMO and its prompt initiation are critical to improved outcomes. The use of venovenous-ECMO became the preferred procedure for PGD rather than venoarterial-ECMO. However, the current ECMO strategy has limitations, and using ECMO to manage patients with PGD is not sufficiently effective. Further studies are required to develop this promising technology. en-copyright= kn-copyright= en-aut-name=MatsubaraKei en-aut-sei=Matsubara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=2 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=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= en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=primary graft dysfunction kn-keyword=primary graft dysfunction en-keyword=extracorporeal membrane oxygenation kn-keyword=extracorporeal membrane oxygenation en-keyword=ex vivo lung perfusion kn-keyword=ex vivo lung perfusion END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=17 article-no= start-page=6102 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Risk Factors for Perioperative Urinary Tract Infection After Living Donor Kidney Transplantation Characterized by High Prevalence of Desensitization Therapy: A Single-Center Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Limited research exists on risk factors for urinary tract infections (UTIs) in kidney transplant recipients, particularly in high-risk groups such as ABO-incompatible or donor-specific antibody (DSA)-positive cases. Early UTIs, especially within the first month post-transplant, impact on acute rejection and long-term graft outcomes, highlighting the need for risk factor identification and management. Methods: Among 157 living donor kidney transplant cases performed at our institution between 2009 and 2024, 128 patients were included after excluding cases with >72 h of perioperative prophylactic antibiotics or urological complications. UTI was defined as the presence of pyuria and a positive urine culture, accompanied by clinical symptoms requiring antibiotic treatment, occurring within one month post-transplantation. Results: The median onset of UTI was postoperative day 8 (interquartile range, IQR: 6.8?9.3). No subsequent acute rejection episodes were observed. The median serum creatinine at 1 month postoperatively was 1.3 mg/dL (IQR: 1.1?1.7), and this was not significantly different from those who did not develop UTI. In univariate analysis, low or high BMI (<20 or >25), longer dialysis duration (>2.5 years), desensitization therapy (plasmapheresis + rituximab), elevated preoperative neutrophil-to-lymphocyte ratio (NLR) (?3), and longer warm ischemic time (WIT) (?7.8 min) were significantly associated with an increased infection risk of UTI (p = 0.010, 0.036, 0.028, 0.015, and 0.038, respectively). Multivariate analyses revealed that abnormal BMI, longer dialysis duration, desensitization therapy, and longer WIT were independent risk factors for UTI (p = 0.012, 0.031, 0.008, and 0.033, respectively). The incidence of UTI increased with the number of risk factors: 0% (0/16) for zero, 10% (5/48) for one, 31% (16/51) for two, 45% (5/11) for three, and 100% (2/2) for four risk factors. Conclusions: Desensitization therapy, BMI, dialysis duration, and WIT were identified as independent risk factors for perioperative UTI. In patients with risk factors, additional preventive strategies should be considered, with extended antibiotic prophylaxis being one potential option. en-copyright= kn-copyright= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueShota en-aut-sei=Inoue en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokunagaMoto en-aut-sei=Tokunaga en-aut-mei=Moto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KubotaRisa en-aut-sei=Kubota en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 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=20 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, NHO Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, NHO Okayama Medical Center kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Urology, Shimane University Faculty of Medicine kn-affil= affil-num=19 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=20 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=living donor kidney transplantation kn-keyword=living donor kidney transplantation en-keyword=urinary tract infection kn-keyword=urinary tract infection en-keyword=perioperative kn-keyword=perioperative en-keyword=desensitization kn-keyword=desensitization en-keyword=rituximab kn-keyword=rituximab en-keyword=plasmapheresis kn-keyword=plasmapheresis en-keyword=body mass index kn-keyword=body mass index en-keyword=dialysis duration kn-keyword=dialysis duration en-keyword=warm ischemic time kn-keyword=warm ischemic time en-keyword=prophylactic antimicrobials kn-keyword=prophylactic antimicrobials END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=2 article-no= start-page=1 end-page=13 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advancements in systemic therapy for muscle-invasive bladder cancer: A systematic review from the beginning to the latest updates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Context: Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC).
Objective: To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs.
Evidence acquisition: Three databases and ClinicalTrials.gov were searched in October 2024 for eligible RCTs evaluating oncologic outcomes in MIBC patients treated with systemic therapy. We evaluated pathological complete response (pCR), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and adverse events (AEs).
Evidence synthesis: Thirty-three RCTs (including 14 ongoing trials) were included in this systematic review. Neoadjuvant chemotherapy improved OS compared to radical cystectomy alone. Particularly, the VESPER trial demonstrated that dd-MVAC provided oncological benefits over GC alone in terms of pCR rates, OS (HR: 0.71), and PFS (HR: 0.70). Recently, the NIAGARA trial showed that perioperative durvalumab plus GC outperformed GC alone in terms of pCR rates, OS (HR: 0.75), and EFS (HR: 0.68). Despite the lack of data on overall AE rates in the VESPER trial, differential safety profiles in hematologic toxicity were reported between dd-MVAC and durvalumab plus GC regimens. In the adjuvant setting, no study provided the OS benefit from adjuvant chemotherapy. However, only adjuvant nivolumab had significant DFS and OS benefits compared to placebo.
Conclusions: Neoadjuvant chemotherapy remains the current standard of care for MIBC. Durvalumab shed light on the promising impact of ICIs added to neoadjuvant chemotherapy. Nivolumab is the only ICI recommended as adjuvant therapy in patients who harbored adverse pathologic outcomes. Ongoing trials will provide further information on the impact of combination therapy, including chemotherapy, ICIs, and enfortumab vedotin, in both neoadjuvant and adjuvant settings. en-copyright= kn-copyright= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TeohJeremy Yuen-Chun en-aut-sei=Teoh en-aut-mei=Jeremy Yuen-Chun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RajwaPawe? en-aut-sei=Rajwa en-aut-mei=Pawe? kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=QuhalFahad en-aut-sei=Quhal en-aut-mei=Fahad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=PradereBenjamin en-aut-sei=Pradere en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoschiniMarco en-aut-sei=Moschini en-aut-mei=Marco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MikiJun en-aut-sei=Miki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KimuraTakahiro en-aut-sei=Kimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=8 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=9 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=10 en-affil=Department of Urology, San Raffaele Hospital and Scientific Institute kn-affil= affil-num=11 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=12 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=urothelial carcinoma kn-keyword=urothelial carcinoma en-keyword=muscle-invasive kn-keyword=muscle-invasive en-keyword=neoadjuvant kn-keyword=neoadjuvant en-keyword=adjuvant kn-keyword=adjuvant END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=5 article-no= start-page=2787 end-page=2793 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Accuracy of Contrast-enhanced CT in Diagnosing Small-sized cT3a Renal Cell Carcinoma and Analysis of Factors Predicting Downstaging to pT1 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: This study assessed the accuracy of preoperative contrast-enhanced computed tomography (CECT) scans in staging small-sized, locally advanced (cT3a) renal cell carcinoma (RCC) and identified predictors of pathological downstaging following surgery.
Patients and Methods: Seventy-six patients who underwent radical nephrectomy for cT3aN0M0 RCC with tumors ?7 cm were analyzed. Preoperative CECT evaluated features such as venous, peritumoral, or renal sinus fat, and urinary tract invasion, predictive values, and concordance index between radiological and pathological findings were calculated for these categories. The study also examined the impact of clinicopathologic factors on downstaging.
Results: Of 76 patients with cT3 RCC, 37% were down-staged to pT1. Down-staged cases had a higher proportion of male patients and non-clear cell carcinoma (86% vs. 58%, 32% vs. 6%; p=0.02, p=0.007, respectively). Multiple cT3a factors were less common in down-staged cases (4% vs. 23%, p=0.04). Non-clear cell carcinoma was significantly associated with downstaging compared to clear cell carcinoma (75% vs. 30%, p=0.006). Multivariate analysis confirmed non-clear cell carcinoma as an independent predictor (odds ratio=8.2, p=0.01). For venous invasion, CECT sensitivity and positive predictive value were high (73.5% and 83.3%, respectively) and the degree of agreement was substantial (=0.62).
Conclusion: The accuracy of preoperative CECT was acceptable for detecting venous invasion. The downstaging to pT1 occurred in 37% of cT3a RCC cases in the final pathology, with non-clear cell carcinoma being a significant predictor.
en-copyright= kn-copyright= en-aut-name=BEKKUKENSUKE en-aut-sei=BEKKU en-aut-mei=KENSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YOSHINAGAKASUMI en-aut-sei=YOSHINAGA en-aut-mei=KASUMI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=INOUESHOTA en-aut-sei=INOUE en-aut-mei=SHOTA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MITSUIYOSUKE en-aut-sei=MITSUI en-aut-mei=YOSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YAMANOITOMOAKI en-aut-sei=YAMANOI en-aut-mei=TOMOAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KAWADATATSUSHI en-aut-sei=KAWADA en-aut-mei=TATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TOMINAGAYUSUKE en-aut-sei=TOMINAGA en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SADAHIRATAKUYA en-aut-sei=SADAHIRA en-aut-mei=TAKUYA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KATAYAMASATOSHI en-aut-sei=KATAYAMA en-aut-mei=SATOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IWATATAKEHIRO en-aut-sei=IWATA en-aut-mei=TAKEHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NISHIMURASHINGO en-aut-sei=NISHIMURA en-aut-mei=SHINGO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EDAMURAKOHEI en-aut-sei=EDAMURA en-aut-mei=KOHEI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KOBAYASHITOMOKO en-aut-sei=KOBAYASHI en-aut-mei=TOMOKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Contrast?enhanced CT kn-keyword=Contrast?enhanced CT en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma en-keyword=staging kn-keyword=staging en-keyword=T3a kn-keyword=T3a en-keyword=downstaging kn-keyword=downstaging END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=20 article-no= start-page=2979 end-page=2984 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=Two Cases of Esophageal Mucosal Damage Observed after Peroral Endoscopic Myotomy for Esophageal Motility Disorders en-subtitle= kn-subtitle= en-abstract= kn-abstract=This report presents two cases of esophageal mucosal damage following peroral endoscopic myotomy (POEM) for esophageal motility disorders. In the first case, delayed perforation and mediastinitis occurred on postoperative day 15 and the patient was treated with endoscopic clipping and antibiotics. In the second case, although no perforation was observed, extensive mucosal injury developed the day after POEM which was successfully managed by fasting and antibiotic therapy. These findings highlight the need for careful patient management to minimize the risks associated with POEM, while maximizing its therapeutic benefits. en-copyright= kn-copyright= en-aut-name=HirataShoichiro en-aut-sei=Hirata en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatomiTakuya en-aut-sei=Satomi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaeHiroyuki en-aut-sei=Sakae en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ManabeNoriaki en-aut-sei=Manabe en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=hypercontractile esophagus kn-keyword=hypercontractile esophagus en-keyword=jackhammer esophagus kn-keyword=jackhammer esophagus en-keyword=peroral endoscopic myotomy kn-keyword=peroral endoscopic myotomy END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=22 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relay Node Selection Methods for UAV Navigation Route Constructions in Wireless Multi-Hop Network Using Smart Meter Devices en-subtitle= kn-subtitle= en-abstract= kn-abstract=Unmanned aerial vehicles (UAVs) offer solutions to issues like traffic congestion and labor shortages. We developed a distributed UAV management system inspired by virtual circuit and datagram methods in packet-switching networks. By installing houses with wireless terminals, UAVs navigate routes in a multi-hop network, communicating with ground nodes. UAVs are treated as network packets, ground devices are treated as routers, and their connections are treated as links. Activating all nodes as relays increases control message traffic and node load. To optimize connectivity, we minimize relay nodes, connecting non-relay nodes to the nearest relay. This study proposes four relay node selection methods: random selection, two adjacency-based methods, and our innovative approach using Multipoint Relay (MPR) from the Optimized Link State Routing Protocol (OLSR). We evaluated these methods according to their route construction success rates, relay node counts, route lengths, and so on. The MPR-based method proved most effective for UAV route construction. However, fewer relay nodes increase link collisions, and we identify the minimum relay density needed to balance efficiency and conflict reduction. en-copyright= kn-copyright= en-aut-name=OhkawaShuto en-aut-sei=Ohkawa en-aut-mei=Shuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaKiyoshi en-aut-sei=Ueda en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyoshiTakumi en-aut-sei=Miyoshi en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamazakiTaku en-aut-sei=Yamazaki en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoRyo en-aut-sei=Yamamoto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Engineering, Nihon University kn-affil= affil-num=2 en-affil=Graduate School of Engineering, Nihon University kn-affil= affil-num=3 en-affil=College of Systems Engineering and Science, Shibaura Institute of Technology kn-affil= affil-num=4 en-affil=College of Systems Engineering and Science, Shibaura Institute of Technology kn-affil= affil-num=5 en-affil=Graduate School of Informatics and Engineering, The University of Electro-Communications kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=network of wireless devices kn-keyword=network of wireless devices en-keyword=UAV delivery kn-keyword=UAV delivery en-keyword=ad hoc network kn-keyword=ad hoc network 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=16 cd-vols= no-issue=8 article-no= start-page=709 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=A Phrase Fill-in-Blank Problem in a Client-Side Web Programming Assistant System en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mastering client-side Web programming is essential for the development of responsive and interactive Web applications. To support novice studentsf self-study, in this paper, we propose a novel exercise format called the phrase fill-in-blank problem (PFP) in the Web Programming Learning Assistant System (WPLAS). A PFP instance presents a source code with blanked phrases (a set of elements) and corresponding Web page screenshots. Then, it requests the user to fill in the blanks, and the answers are automatically evaluated through string matching with predefined correct answers. By increasing blanks, PFP can come close to writing a code from scratch. To facilitate scalable and context-aware question creation, we implemented the PFP instance generation algorithm in Python using regular expressions. This approach targets meaningful code segments in HTML, CSS, and JavaScript that reflect the interactive behavior of front-end development. For evaluations, we generated 10 PFP instances for basic Web programming topics and 5 instances for video games and assigned them to students at Okayama University, Japan, and the State Polytechnic of Malang, Indonesia. Their solution results show that most students could solve them correctly, indicating the effectiveness and accessibility of the generated instances. In addition, we investigated the ability of generative AI, specifically ChatGPT, to solve the PFP instances. The results show 86.7% accuracy for basic-topic PFP instances. Although it still cannot fully find answers, we must monitor progress carefully. In future work, we will enhance PFP in WPLAS to handle non-unique answers by improving answer validation for flexible recognition of equivalent responses. en-copyright= kn-copyright= en-aut-name=QiHuiyu en-aut-sei=Qi en-aut-mei=Huiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiZhikang en-aut-sei=Li en-aut-mei=Zhikang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Sandi KyawHtoo Htoo en-aut-sei=Sandi Kyaw en-aut-mei=Htoo Htoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KaoWen Chung en-aut-sei=Kao en-aut-mei=Wen Chung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Electrical Engineering, National Taiwan Normal University kn-affil= en-keyword=Web client programming kn-keyword=Web client programming en-keyword=Web game kn-keyword=Web game en-keyword=HTML kn-keyword=HTML en-keyword=CSS kn-keyword=CSS en-keyword=JavaScript kn-keyword=JavaScript en-keyword=phrase fill-in-blank problem kn-keyword=phrase fill-in-blank problem en-keyword=regular expression kn-keyword=regular expression en-keyword=generative AI kn-keyword=generative AI END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=8 article-no= start-page=333 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Verilog Programming Learning Assistant System Focused on Basic Verilog with a Guided Learning Method en-subtitle= kn-subtitle= en-abstract= kn-abstract=With continuous advancements in semiconductor technology, mastering efficient designs of high-quality and advanced chips has become an important part of science and technology education. Chip performances will determine the futures of various aspects of societies. However, novice students often encounter difficulties in learning digital chip designs using Verilog programming, a common hardware design language. An efficient self-study system for supporting them that can offer various exercise problems, such that any answer is marked automatically, is in strong demand. In this paper, we design and implement a web-based Verilog programming learning assistant system (VPLAS), based on our previous works on software programming. Using a heuristic and guided learning method, VPLAS leads students to learn the basic circuit syntax step by step, until they acquire high-quality digital integrated circuit design abilities through self-study. For evaluation, we assign the proposal to 50 undergraduate students at the National Taipei University of Technology, Taiwan, who are taking the introductory chip-design course, and confirm that their learning outcomes using VPLAS together are far better than those obtained when following a traditional method. In our final statistics, students achieved an average initial accuracy rate of over 70% on their first attempts at answering questions after learning through our websitefs tutorials. With the help of the systemfs instant automated grading and rapid feedback, their average accuracy rate eventually exceeded 99%. This clearly demonstrates tha en-copyright= kn-copyright= en-aut-name=HsiehPin-Chieh en-aut-sei=Hsieh en-aut-mei=Pin-Chieh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FangTzu-Lun en-aut-sei=Fang en-aut-mei=Tzu-Lun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JinShaobo en-aut-sei=Jin en-aut-mei=Shaobo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangYuyan en-aut-sei=Wang en-aut-mei=Yuyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FanYu-Cheng en-aut-sei=Fan en-aut-mei=Yu-Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Electronic Engineering, National Taipei University of Technology kn-affil= affil-num=2 en-affil=Department of Electronic Engineering, National Taipei University of Technology kn-affil= affil-num=3 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Electronic Engineering, National Taipei University of Technology kn-affil= en-keyword=Verilog kn-keyword=Verilog en-keyword=online learning kn-keyword=online learning en-keyword=guided learning kn-keyword=guided learning en-keyword=heuristic learning kn-keyword=heuristic learning en-keyword=programming learning assistant system kn-keyword=programming learning assistant system en-keyword=Verilog web-based kn-keyword=Verilog web-based END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=34964 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251007 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Periodontitis associated with Porphyromonas gingivalis infection is a risk factor for infertility through uterine hypertrophy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontitis has recently been recognized as a potential risk factor for infertility due to its adverse effect on conception, although the underlying mechanisms remain unclear. This study investigated serum IgG antibody titers against periodontopathogenic bacteria in women with unexplained infertility and investigated how periodontal inflammation affects pregnancy and uterine function using a ligature-induced periodontitis mouse model infected with Porphyromonas gingivalis (Pg). IgG antibody titers against seven periodontopathogenic bacteria strains were measured by ELISA in 76 spontaneously pregnant women and 70 women undergoing infertility treatment. In the in vivo study, periodontitis mice were bred four weeks after periodontitis induction. Birth numbers, newborn weights, and gestation periods were assessed. To evaluate periodontal inflammation, alveolar bone, serum, and uterus was collected before mating. Uterine tissue was evaluated through histological and immunohistochemical staining. Women receiving infertility treatment were significantly older and had higher IgG titers against three Pg strains. Periodontitis mice had fewer births, lower newborn weights, and increased uterine cross-sectional areas. Additionally, elevated estrogen receptor and progesterone receptor expression levels were observed in endometrial and stromal tissues. These results suggest that periodontitis may cause uterine hypertrophy and hormone receptor changes, potentially impairing pregnancy. en-copyright= kn-copyright= en-aut-name=Kamei-NagataChiaki en-aut-sei=Kamei-Nagata en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=SakoHidefumi en-aut-sei=Sako en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaidaKyosuke en-aut-sei=Sakaida en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakayamaMasa-aki en-aut-sei=Nakayama en-aut-mei=Masa-aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=MandaiHiroki en-aut-sei=Mandai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Kubota-TakamoriMoyuka en-aut-sei=Kubota-Takamori en-aut-mei=Moyuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KiyamaFumiko en-aut-sei=Kiyama en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraiKimito en-aut-sei=Hirai en-aut-mei=Kimito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IkedaAtsushi en-aut-sei=Ikeda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Takeuchi-HatanakaKazu en-aut-sei=Takeuchi-Hatanaka en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=Tai-TokuzenMasako en-aut-sei=Tai-Tokuzen en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakamotoAi en-aut-sei=Sakamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiyokawaMachiko en-aut-sei=Kiyokawa en-aut-mei=Machiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamanishiTomomi en-aut-sei=Yamanishi en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OdaTakashi en-aut-sei=Oda en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakigawaMasayuki en-aut-sei=Takigawa en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MiyakeTakahito en-aut-sei=Miyake en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 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=23 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=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=16 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=17 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=18 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=19 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=20 en-affil=Miyake Hello Dental Clinic, Pediatric Dentistry and Orthodontics kn-affil= affil-num=21 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=22 en-affil=Center for Reproductive Medicine, Miyake Clinic kn-affil= affil-num=23 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Infertility kn-keyword=Infertility en-keyword=Periodontitis kn-keyword=Periodontitis en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=Chronic inflammation kn-keyword=Chronic inflammation en-keyword=Uterus kn-keyword=Uterus en-keyword=Sex hormone receptor kn-keyword=Sex hormone receptor END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The response to thermospermine is fine-tuned by the balance between SAC51 and LHW family proteins in Arabidopsis thaliana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thermospermine negatively regulates xylem formation. In Arabidopsis, SAC51 and SACL3, members of the SAC51 gene family encoding basic loop-helix-loop (bHLH) proteins play a key role in this regulation. These mRNAs contain an upstream open-reading-frame (uORF) that is highly conserved across species, and its inhibitory effect on the main ORF translation is alleviated by thermospermine. A double knockout of SAC51 and SACL3 results in thermospermine insensitivity at high concentrations that normally inhibit xylem formation and shoot growth in the wild type. Conversely, uORF mutants of SAC51, SACL3, and SACL1 suppress the excessive xylem formation and dwarf phenotype of acl5, a mutant defective in thermospermine biosynthesis. In this study, we generated genome-edited uORF mutants of SACL2 and confirmed that they partially recover the acl5 phenotype. All uORF mutants exhibited increased sensitivity to thermospermine. SACL3 represses the function of LHW, a key bHLH transcription factor required for xylem proliferation, through direct interaction. We found that the lhw mutant is also hypersensitive to thermospermine, while this sensitivity was suppressed by the sac51 sacl3 double knockout. Yeast two-hybrid assays demonstrated that all four SAC51 family members interact with LHW and its family members. These findings suggest that overaccumulation of SAC51 family proteins leads to thermospermine hypersensitivity by repressing the function of LHW family proteins, whose activity must be fine-tuned to ensure proper xylem development. en-copyright= kn-copyright= en-aut-name=XuYao en-aut-sei=Xu en-aut-mei=Yao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaraumiMitsuru en-aut-sei=Saraumi en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToyoshimaTomohiko en-aut-sei=Toyoshima en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MotoseHiroyasu en-aut-sei=Motose en-aut-mei=Hiroyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiTaku en-aut-sei=Takahashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=LHW family kn-keyword=LHW family en-keyword=SAC51 family kn-keyword=SAC51 family en-keyword=thermospermine kn-keyword=thermospermine en-keyword=xylem kn-keyword=xylem END start-ver=1.4 cd-journal=joma no-vol=123 cd-vols= no-issue=5 article-no= start-page=e70476 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=RNA processing/modifying enzymes play key roles in the response to thermospermine in Arabidopsis thaliana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thermospermine is involved in negative regulation of xylem differentiation by enhancing the translation of mRNAs of the SAC51 gene family in Arabidopsis (Arabidopsis thaliana). These mRNAs contain conserved upstream open reading frames (uORFs) that interfere with the translation of the main ORF. To investigate the mechanism by which thermospermine acts in this process, we isolated mutants insensitive to thermospermine, named eitsf. We show that the four genes responsible for these mutants, its1 to its4, encode: (i) a homolog of SPOUT RNA methyltransferase, (ii) an rRNA pseudouridine synthase CBF5/NAP57, (iii) a putative spliceosome disassembly factor STIPL1/NTR1, and (iv) a plant-specific RNA-binding protein PHIP1. These four mutants were found to have much higher levels of thermospermine than the wild-type. While all these mutants except its1 appear almost normal, they enhance the dwarf phenotype of a mutant of ACL5, which encodes thermospermine synthase, resulting in tiny plants resembling a double knockout of ACL5 and SACL3, a member of the SAC51 family. Reporter assays revealed that GUS activity from the CaMV 35S promoter-SAC51 5-GUS fusion construct was significantly reduced in its1 and its4 or not affected in its2 and its3, while it was slightly increased in its1, its3, and its4, or not changed in its2 by thermospermine. These findings underscore the critical role of RNA processing and modification in the thermospermine-dependent translational regulation of uORF-containing transcripts. en-copyright= kn-copyright= en-aut-name=SaraumiMitsuru en-aut-sei=Saraumi en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakahiro en-aut-sei=Tanaka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoyamaDaiki en-aut-sei=Koyama en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiYoshitaka en-aut-sei=Nishi en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiYoshihiro en-aut-sei=Takahashi en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MotoseHiroyasu en-aut-sei=Motose en-aut-mei=Hiroyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiTaku en-aut-sei=Takahashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Engineering, Kyushu Sangyo University kn-affil= affil-num=5 en-affil=Department of Life Science, Faculty of Life Science, Kyushu Sangyo 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= en-keyword=thermospermine kn-keyword=thermospermine en-keyword=uORF kn-keyword=uORF en-keyword=translation kn-keyword=translation en-keyword=xylem kn-keyword=xylem en-keyword=RNA methyltransferase kn-keyword=RNA methyltransferase en-keyword=pseudouridine synthase kn-keyword=pseudouridine synthase en-keyword=SPOUT domain kn-keyword=SPOUT domain en-keyword=spliceosome disassembly kn-keyword=spliceosome disassembly END start-ver=1.4 cd-journal=joma no-vol=105 cd-vols= no-issue=4 article-no= start-page=1157 end-page=1167 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of environmental conditions on seed germination and seedling growth in Cuscuta campestris en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dodder (Cuscuta) is an obligate parasitic plant that cannot survive without a host and causes significant damage to crop yields. To understand its growth characteristics before parasitism, we examined the effects of environmental conditions on seed germination and seedling growth in Cuscuta campestris Yunck. Among various factors, we focused on the effects of light, pH, temperature, sugars, salts, hormones, amino acids and polyamines on seeds sown on agar plates. Regarding the effect of light on germination, far-red light was preferable rather than red light and the reversible response of seeds to red and far-red light was confirmed, implicating a phytochrome-mediated signaling pathway opposite to that in many seed plants. Among the amino acids, aspartic acid and alanine had a promotive effect, while histidine had an inhibitory effect on germination. We further found that, in addition to gibberellic acid, methyl jasmonate stimulated both germination and shoot elongation. While 2,4-D extended the viability of trichomes around the root cap, kinetin induced the formation of scale leaves on the shoot and undifferentiated cell clusters at the base of the shoot and root tip. Real-time reverse transcriptase PCR (RT-PCR) experiments confirmed that the expression of a putative RbcS gene for photosynthesis showed no response to light, whereas that of a Phytochrome A homolog increased in the dark. Our results indicate that some of the molecular mechanisms involved in responding to light and hormone signals are uniquely modified in dodder seedlings, providing clues for understanding the survival strategy of parasitic plants. en-copyright= kn-copyright= en-aut-name=NagaoKoki en-aut-sei=Nagao en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiTaku en-aut-sei=Takahashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaRyusuke en-aut-sei=Yokoyama en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=Graduate School of Life Sciences, Tohoku University kn-affil= en-keyword=Cuscuta kn-keyword=Cuscuta en-keyword=Environmental conditions kn-keyword=Environmental conditions en-keyword=Germination kn-keyword=Germination en-keyword=Hormone responses kn-keyword=Hormone responses en-keyword=Seedling growth kn-keyword=Seedling growth END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=34768 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251006 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Continuous glucose monitoring reveals periodontitis-induced glucose variability, insulin resistance, and gut microbiota dysbiosis in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diabetes mellitus (DM) management has advanced from self-monitoring blood glucose (SMBG) to continuous glucose monitoring (CGM), which better prevents complications. However, the influence of periodontitis?a common DM complication?on glucose variability is unclear. This study examined glucose variability in mice with periodontitis using CGM. Periodontitis was induced in 9-week-old male C57BL/6J mice via silk ligatures around the upper second molars. Glucose levels were monitored over 14 days with CGM, validated by SMBG. On day 14, samples were collected to assess alveolar bone resorption and serum levels of tumor necrosis factor- (TNF-), insulin, and amyloid A. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted to evaluate insulin resistance. Gut microbiota diversity was also analyzed. By day 10, mice with periodontitis exhibited higher mean glucose levels and time above range than controls. On day 14, serum insulin and amyloid A levels significantly increased, while TNF- remained unchanged. GTT and ITT indicated insulin resistance. Microbiota analysis showed reduced alpha- and altered beta-diversity, with decreased Coprococcus spp. and increased Prevotella spp., linking dysbiosis to insulin resistance. Periodontitis disrupts glucose regulation by promoting insulin resistance and gut microbiota imbalance, leading to significant glucose variability. en-copyright= kn-copyright= en-aut-name=Kubota-TakamoriMoyuka en-aut-sei=Kubota-Takamori en-aut-mei=Moyuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=Kamei-NagataChiaki en-aut-sei=Kamei-Nagata en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KiyamaFumiko en-aut-sei=Kiyama en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiraiKimito en-aut-sei=Hirai en-aut-mei=Kimito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkuboKeisuke en-aut-sei=Okubo en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraShin en-aut-sei=Nakamura en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IkedaAtsushi en-aut-sei=Ikeda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SaitoTsugumichi en-aut-sei=Saito en-aut-mei=Tsugumichi 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=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei University kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Continuous glucose monitoring kn-keyword=Continuous glucose monitoring en-keyword=Periodontal disease kn-keyword=Periodontal disease en-keyword=Insulin resistance kn-keyword=Insulin resistance en-keyword=Chronic inflammation kn-keyword=Chronic inflammation en-keyword=Gut flora kn-keyword=Gut flora END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=e94062 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251007 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Refractive Error Correction With Glasses in Congenital Ocular Fundus Anomalies: A Retrospective Series of 18 Children With Different Disease Entities Followed Up for More Than 10 Years en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Children with congenital anomalies of the posterior segment of the eye are in the process of visual development, and thus, their refractive errors should be detected by cycloplegic refraction testing to prescribe full-correction glasses, if required, and to help their visual acuity develop with growth. This study aimed to review refractive correction in children with congenital ocular fundus anomalies.
Methods: A retrospective review was conducted on 18 consecutive children (11 female and seven male children) who were diagnosed with ocular fundus anomalies and followed for 10 years or more by a single ophthalmologist at a referral-based hospital. The age at the initial visit ranged from 10 days after birth to 11 years, with a median of one year and four months, and the age at the last visit ranged from 10 to 32 years, with a median of 15 years. The follow-up periods ranged from 10 to 21 years at a median of 15 years.
Results: The diagnoses were familial exudative vitreoretinopathy (FEVR) in eight children, persistent fetal vasculature (PFV) in five, morning glory disc anomaly in two, optic nerve and choroidal coloboma (CHARGE syndrome) in two, and Coats disease in one. Full-correction glasses were prescribed in eight children, while the remaining 10 children did not wear glasses. Among nine children with the uncorrected visual acuity of 1.0 or better in one eye and the visual acuity in the other eye ranging from light perception to 0.01, eight children did not wear glasses, and one child wore glasses with hyperopic correction. The diagnoses in these nine children were PFV in five children, morning glory disc anomaly in two, FEVR in one, and Coats disease in one. In seven children who wore full-correction glasses, the best corrected visual acuity in the better eye ranged from 0.2 to 0.9 at a median of 0.5. In contrast, the visual acuity in the other eye ranged from light perception to 0.1 at a median of 0.03. The diagnoses of these seven children were FEVR in five children and CHARGE syndrome in two. The five children with FEVR showed myopic astigmatism in both eyes, while the two children with CHARGE syndrome showed hyperopic astigmatism in both eyes.
Conclusion: Children with unilateral eye anomalies such as PFV and morning glory disc anomaly did not wear glasses since their healthy eyes had good uncorrected visual acuity. In contrast, children with involvement of both eyes in FEVR and CHARGE syndrome wore full-correction glasses. Rough information regarding full-correction glasses in each category would help clinicians cope with rare congenital eye diseases. However, this conclusion is generally applicable to the standard practice of pediatric ophthalmology. 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= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=charge syndrome kn-keyword=charge syndrome en-keyword=choroidal coloboma kn-keyword=choroidal coloboma en-keyword=coats disease kn-keyword=coats disease en-keyword=congenital eye anomalies kn-keyword=congenital eye anomalies en-keyword=cycloplegic refraction kn-keyword=cycloplegic refraction en-keyword=familial exudative vitreoretinopathy (fevr) kn-keyword=familial exudative vitreoretinopathy (fevr) en-keyword=full-correction glasses kn-keyword=full-correction glasses en-keyword=morning glory disc anomaly kn-keyword=morning glory disc anomaly en-keyword=optic nerve coloboma kn-keyword=optic nerve coloboma en-keyword=persistent fetal vasculature (pfv) kn-keyword=persistent fetal vasculature (pfv) END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=4 article-no= start-page=51 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target. en-copyright= kn-copyright= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HikitaTakao en-aut-sei=Hikita en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MashimaTomoha en-aut-sei=Mashima en-aut-mei=Tomoha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TorigataKosuke en-aut-sei=Torigata en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ThuYin Min en-aut-sei=Thu en-aut-mei=Yin Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HabuTomohiro en-aut-sei=Habu en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=ItoSachio en-aut-sei=Ito en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=School of Medicine, Kobe University kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Thoracic Surgery, National Hospital Organization, Shikoku Cancer Center kn-affil= affil-num=13 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cancer-associated fibroblast kn-keyword=Cancer-associated fibroblast en-keyword=Superoxide dismutase 3 kn-keyword=Superoxide dismutase 3 en-keyword=Lymphangiogenesis kn-keyword=Lymphangiogenesis en-keyword=Angiogenesis kn-keyword=Angiogenesis en-keyword=Metastasis kn-keyword=Metastasis en-keyword=Lung adenocarcinoma kn-keyword=Lung adenocarcinoma END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=11 article-no= start-page=102658 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pathophysiology and Therapeutic Needs in Nonobstructive Hypertrophic Cardiomyopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypertrophic cardiomyopathy (HCM) affects individuals worldwide with an estimated prevalence of over 1 in 500 individuals. Nonobstructive HCM accounts for approximately 30% to 70% of cases, is extremely heterogeneous, and is associated with a notable degree of morbidity, including daily life limitations, ventricular tachyarrhythmias, progression to heart failure, and atrial fibrillation. No approved pharmaceutical therapies target the pathophysiology of nonobstructive HCM, although several clinical trials are underway. This narrative review provides a comprehensive overview of nonobstructive HCM, focusing on epidemiology, natural history, genetics, pathophysiology, clinical manifestations, diagnosis, burden of disease, and current treatments and ongoing clinical trials. en-copyright= kn-copyright= en-aut-name=DesaiMilind Y. en-aut-sei=Desai en-aut-mei=Milind Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MauriziNiccolo en-aut-sei=Maurizi en-aut-mei=Niccolo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BiaginiElena en-aut-sei=Biagini en-aut-mei=Elena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=CharronPhilippe en-aut-sei=Charron en-aut-mei=Philippe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FernandesFabio en-aut-sei=Fernandes en-aut-mei=Fabio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Gonz?lez-L?pezEsther en-aut-sei=Gonz?lez-L?pez en-aut-mei=Esther kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=van HaelstPaul L. en-aut-sei=van Haelst en-aut-mei=Paul L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaugaaKristina Hermann en-aut-sei=Haugaa en-aut-mei=Kristina Hermann kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KramerChristopher M. en-aut-sei=Kramer en-aut-mei=Christopher M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MederBenjamin en-aut-sei=Meder en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MichelsMichelle en-aut-sei=Michels en-aut-mei=Michelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OwensAnjali en-aut-sei=Owens en-aut-mei=Anjali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=ElliottPerry en-aut-sei=Elliott en-aut-mei=Perry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=HCM Center, Department of Cardiovascular Medicine, Cleveland Clinic kn-affil= affil-num=2 en-affil=Cardiomyopathy Unit, Careggi University Hospital kn-affil= affil-num=3 en-affil=Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna kn-affil= affil-num=4 en-affil=European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart) kn-affil= affil-num=5 en-affil=InCor, Faculdade de Medicina da Universidade de S?o Paulo kn-affil= affil-num=6 en-affil=Puerta de Hierro Majadahonda University Hospital, Health Research Institute of the Puerta de Hierro Majadahonda-Segovia de Arana University Hospital (IDIPHISA) kn-affil= affil-num=7 en-affil=Cardiovascular Division, Department of Medicine, University of Virginia Health kn-affil= affil-num=8 en-affil=Cardiovascular Division, Department of Medicine, University of Virginia Health kn-affil= affil-num=9 en-affil=Cardiovascular Division, Department of Medicine, University of Virginia Health kn-affil= affil-num=10 en-affil=Department of Internal Medicine III, Institute for Cardiomyopathies, University of Heidelberg kn-affil= affil-num=11 en-affil=European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart) kn-affil= affil-num=12 en-affil=Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=UCL Institute of Cardiovascular Science and St Bartholomewfs Hospital kn-affil= en-keyword=heart failure kn-keyword=heart failure en-keyword=hypertrophic cardiomyopathy kn-keyword=hypertrophic cardiomyopathy en-keyword=nonobstructive kn-keyword=nonobstructive 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)? Methods We collected clinical data of patients with an eGFR? 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? Methods An established hPSC cardiac differentiation protocol employing sequential GSK3 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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Establishment of a regenerative endodontic procedures model of mature mouse teeth and evaluation of the wound healing process en-subtitle= kn-subtitle= en-abstract= kn-abstract=As the pulp regeneration for non-vital teeth is one of the ultimate clinical achievements, regenerative endodontic procedures (REPs) have become the most explored treatment modality. In this technique, periodontal tissue is guided from the apical region into the root canal and pulp chamber to promote attachment. It is well established that immature teeth are effective targets for treatment. However, the indications for this treatment have not yet expanded sufficiently to encompass mature teeth with closed apical apex. In the present study, a mouse model of REPs in mature teeth was established, employing the maxillary first molar mesial root. CT analyses disclosed that the distance from the occlusal surface to the physiological apex of the maxillary first molar mesial root in mice is 2.14 mm?}?0.08 mm, and the distance from the occlusal surface to the periapical alveolar bone is 2.46 mm?}?0.10 mm. Mesial root canal was treated with several sizes of k-files, and 15# k-file was identified as the most suitable k-file for use (P?=?0.0007). During the regenerative process, spindle-shaped fibroblast-like cells, fibrous tissue formation, and mineralized tissue formation were identified on days 14 and 28. This study demonstrated that it is feasible to use the maxillary first molar mesial root as a REPs model for mature teeth and provided a detailed protocol and analysis of the healing process. en-copyright= kn-copyright= en-aut-name=WangXiuting en-aut-sei=Wang en-aut-mei=Xiuting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiShigeki en-aut-sei=Suzuki en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsaiShin-Ho en-aut-sei=Tsai en-aut-mei=Shin-Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagasakiKarin en-aut-sei=Nagasaki en-aut-mei=Karin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FahrezaRahmad Rifqi en-aut-sei=Fahreza en-aut-mei=Rahmad Rifqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriMasato en-aut-sei=Omori en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamadaSatoru en-aut-sei=Yamada en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=2 en-affil=Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=5 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=6 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=7 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= en-keyword=Regenerative endodontic procedures kn-keyword=Regenerative endodontic procedures en-keyword=Establishment of protocols kn-keyword=Establishment of protocols en-keyword=Mouse experimental model kn-keyword=Mouse experimental model en-keyword=Mature teeth kn-keyword=Mature teeth END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=18 article-no= start-page=2927 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250911 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lacticaseibacillus rhamnosus Probio-M9 Alters the Gut Microbiota and Mitigates Pulmonary Hypertension in a Rat Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Intestinal microbiota plays an important role in the progression of pulmonary hypertension (PH). Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown protective effects against inflammation and remodeling. We investigated whether Probio-M9 supplementation could improve the pathology of PH. Methods: The monocrotaline (MCT)-induced PH model rats are created followed by Probio-M9 treatment. Microbiota and pathological analyses were performed to investigate the therapeutic effects of Probio-M9. Results: Probio-M9 significantly suppressed cardiovascular remodeling and reduced mortality in rats. Analysis of the fecal microbiota revealed that Probio-M9 significantly altered the gut microbiota of MCT model rats. Specifically, Alistipes sp009774895 and Duncaniella muris populations increased, whereas Limosilactobacillus reuteri_D, Ligilactobacillus apodeme and Monoglobus sp900542675 decreased compared to those in the MCT group. Focusing on the expression of GPNMB in macrophages and the localization of CD44, we found that the number of these cells increased in the MCT group but significantly decreased with Probio-M9 treatment. In lung tissue from PH patients, more GPNMB-positive macrophages were found than non-PH lungs, and an increase in CD44-positive cells was confirmed in the vicinity of GPNMB. Conclusions: Probio-M9 had a significant impact on the intestinal microbiota and GPNMB/CD44 positive cells in the lungs of PH rats. en-copyright= kn-copyright= en-aut-name=ZhaoZhixin en-aut-sei=Zhao en-aut-mei=Zhixin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiGaopeng en-aut-sei=Li en-aut-mei=Gaopeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhmichiKiyomi en-aut-sei=Ohmichi en-aut-mei=Kiyomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiXiaodong en-aut-sei=Li en-aut-mei=Xiaodong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhaoFeiyan en-aut-sei=Zhao en-aut-mei=Feiyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshikawaKaori en-aut-sei=Ishikawa en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshikawaRyou en-aut-sei=Ishikawa en-aut-mei=Ryou 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=YokotaNaoya en-aut-sei=Yokota en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SunZhihong en-aut-sei=Sun en-aut-mei=Zhihong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuraharaLin Hai en-aut-sei=Kurahara en-aut-mei=Lin Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=3 en-affil=Department of Diagnostic Pathology, Kagawa University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=5 en-affil=Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University kn-affil= affil-num=6 en-affil=Department of General Medicine, Kagawa University Hospital kn-affil= affil-num=7 en-affil=Department of Diagnostic Pathology, Kagawa University Hospital kn-affil= affil-num=8 en-affil=Center for Advanced Heart Failure, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University kn-affil= affil-num=10 en-affil=Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= en-keyword=pulmonary artery remodeling kn-keyword=pulmonary artery remodeling en-keyword=probiotics kn-keyword=probiotics en-keyword=gut microbiota kn-keyword=gut microbiota en-keyword=macrophages kn-keyword=macrophages en-keyword=GPNMB kn-keyword=GPNMB en-keyword=CD44 kn-keyword=CD44 END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=5 article-no= start-page=939 end-page=948 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study on an Effective Coolant Supply Method in the Side Plunge Grinding Process en-subtitle= kn-subtitle= en-abstract= kn-abstract=Grinding is widely used for finishing components with journal and thrust surfaces, such as crankshafts. Side-plunge grinding enables the simultaneous finishing of thrust and cylindrical surfaces in a single plunge. However, compared to cylindrical grinding, it involves a larger contact area between the grinding wheel and the workpiece, leading to increased heat generation. In particular, poor coolant penetration near internal corners can degrade surface quality, potentially causing stress concentrations and cracks. To enhance coolant effectiveness in side-plunge grinding, this study installs a high-pressure nozzle that supplies coolant from the side of the grinding wheel. The effectiveness of this setup is experimentally verified. Additionally, the distribution of coolant flow within the contact area between the grinding wheel and the workpiece is measured to determine the optimal nozzle position for efficient coolant delivery. The nozzlefs performance is evaluated by measuring the workpiece surface temperature using a wire/workpiece thermocouple, the amount of coolant discharged from the grinding wheel, and the residual stress distribution. The results show that coolant penetrates the grinding wheel and effectively reaches the grinding zone, enhancing the cooling effect. This study clarifies the relationship between effective coolant supply and the position of the side nozzle. Considering physical constraints, such as potential interference during grinding, the optimal nozzle location is as close as possible to both the edge of the grinding wheel and the workpiece. This positioning ensures maximum coolant delivery, reduces grinding temperature, and helps suppress drastic variations in residual stress. en-copyright= kn-copyright= en-aut-name=GaoLingxiao en-aut-sei=Gao en-aut-mei=Lingxiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujimotoTaichi en-aut-sei=Fujimoto en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KodamaHiroyuki en-aut-sei=Kodama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhashiKazuhito en-aut-sei=Ohashi en-aut-mei=Kazuhito 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=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=grinding kn-keyword=grinding en-keyword=thrust surface kn-keyword=thrust surface en-keyword=grinding temperature kn-keyword=grinding temperature en-keyword=coolant flow kn-keyword=coolant flow en-keyword=residual stress kn-keyword=residual stress END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=7 article-no= start-page=1044 end-page=1060 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=Oxygen supply is a prerequisite for response to aluminum in cultured cells of tobacco (Nicotiana tabacum) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Responses to aluminum (Al) were investigated in tobacco cells (cell line SL) in a calcium-sucrose solution for up to 24 h under shaking (aerobic) condition. Microarray analysis of upregulated and downregulated genes under Al exposure and following Gene Ontology (GO) enrichment analysis of biological process category revealed only one GO term to be enriched for the upregulated genes, gresponse to chitin,h annotated with genes encoding transcription factors (NtERF1 and NtMYB3) and MAP kinase (WIPK), and nine GO terms for the downregulated genes, including gcell wall looseningh and glipid transport,h annotated with genes encoding expansin (NtEXPA4) and lipid transfer protein (LTP)/LTP-like (NtLTP3 and NtEIG-C29), respectively. Al triggered the production of nitric oxide (NO) then reactive oxygen species (ROS). Addition of NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide decreased the levels of NO and a part of the transcriptional changes described above, but increased the levels of ROS and a loss of growth capacity, suggesting a role of the NO to induce the transcriptional changes partly and to repress these toxic responses under Al exposure. Under non-shaking (anaerobic) condition, the cells exhibited upregulation of several hypoxia-responsive genes. The cells exposed to Al exhibited the same level of Al accumulation but much lower levels of the Al responses including NO production, ROS production, a loss of growth capacity, citrate secretion, and a part of the transcriptional changes described above, compared with the cells under shaking condition. These results suggest that coexistence of oxygen with Al is necessary to trigger the Al responses related to toxicity and tolerance. en-copyright= kn-copyright= en-aut-name=TsuchiyaYoshiyuki en-aut-sei=Tsuchiya en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasakiTakayuki en-aut-sei=Sasaki en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoYoko en-aut-sei=Yamamoto en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=aluminum toxicity kn-keyword=aluminum toxicity en-keyword=aluminum-responsive genes kn-keyword=aluminum-responsive genes en-keyword=cell wall loosening kn-keyword=cell wall loosening en-keyword=chitin-responsive genes kn-keyword=chitin-responsive genes en-keyword=dioxygen kn-keyword=dioxygen en-keyword=hypoxia kn-keyword=hypoxia 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=16 cd-vols= no-issue=1 article-no= start-page=8226 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=Persistent homology elucidates hierarchical structures responsible for mechanical properties in covalent amorphous solids en-subtitle= kn-subtitle= en-abstract= kn-abstract=Understanding how atomic-level structures govern the mechanical properties of amorphous materials remains a fundamental challenge in solid-state physics. Under mechanical loading, amorphous materials exhibit simple affine and spatially inhomogeneous nonaffine displacements that contribute to the elastic modulus through the Born (affine) and nonaffine terms, respectively. The differences between soft local structures characterized by small Born terms or large nonaffine displacements have yet to be elucidated. This challenge is particularly complex in covalent amorphous materials such as silicon, where the medium-range order (MRO) plays a crucial role in the network structure. To address these issues, we combined molecular dynamics simulations with persistent homology analysis. Our results reveal that local structures with small Born terms are governed by short-range characteristics, whereas those with large nonaffine displacements exhibit hierarchical structures in which short-range disorder is embedded within the MRO. These hierarchical structures are also strongly correlated with low-energy localized vibrational excitations. Our findings demonstrate that the mechanical responses and dynamic properties of covalent amorphous materials are intrinsically linked to the MRO, providing a framework for understanding and tailoring their properties. en-copyright= kn-copyright= en-aut-name=MinamitaniEmi en-aut-sei=Minamitani en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraTakenobu en-aut-sei=Nakamura en-aut-mei=Takenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ObayashiIppei en-aut-sei=Obayashi en-aut-mei=Ippei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizunoHideyuki en-aut-sei=Mizuno en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=SANKEN, The University of Osaka kn-affil= affil-num=2 en-affil=Department of Materials and Chemistry Materials DX Research Center, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=3 en-affil=Center for Artificial Intelligence and Mathematical Data Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Arts and Sciences, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=20056 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pharmacokinetics and the effectiveness of pyrogen-free bioabsorbable wet adhesives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bioabsorbable materials are essential for advanced therapies, including surgical sealing, cell therapy, and drug delivery. Natural bioabsorbable materials, including collagen and hyaluronic acid, have better biocompatibility than synthetic bioabsorbable polymers; however, they are mainly derived from animals, presenting infection risks. Non-animal origin polymers have a lower molecular weight than those of animal origins. Their viscosity increases with increase in molecular weight, making endotoxin removal difficult. Here, using the phosphoryl chloride disposal method, we present a strategy for synthesizing pyrogen-free bioabsorbable adhesives with controlled molecular weight. Phosphopullulan, a polysaccharide derivative, had less than detectable endotoxin levels and controllable average molecular weight of approximately 300,000 to over 1,400,000. Furthermore, it is important to ensure the safety as well as efficacy of bio-implantable materials. We have evaluated the biosafety of polysaccharide derivatives we are developing, and have examined their cell phagocytosis and pharmacokinetics in vitro and in vivo, and have confirmed that they are safe. We have also evaluated their adhesion to wet tissue adhesions and confirmed that they leak less than existing materials. en-copyright= kn-copyright= en-aut-name=OshimaRisa en-aut-sei=Oshima en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanishiKo en-aut-sei=Nakanishi en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkasakaTsukasa en-aut-sei=Akasaka en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimojiShinji en-aut-sei=Shimoji en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraTeppei en-aut-sei=Nakamura en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkiharaTakumi en-aut-sei=Okihara en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraMariko en-aut-sei=Nakamura en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=TamadaIkkei en-aut-sei=Tamada en-aut-mei=Ikkei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Van MeerbeekBart en-aut-sei=Van Meerbeek en-aut-mei=Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SugayaTsutomu en-aut-sei=Sugaya en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Periodontology, Faculty of Dental Medicine, Hokkaido 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 Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=4 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=5 en-affil=Department of Periodontology, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=Department of Applied Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University kn-affil= affil-num=7 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Department of Clinical Psychology, School of Clinical Psychology, Kyushu University of Medical and Science 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 Plastic and Reconstructive Surgery, Tokyo Metropolitan Childrenfs Medical Center kn-affil= affil-num=11 en-affil=BIOMAT, Department of Oral Health Sciences, & UZ Leuven, Dentistry, KU Leuven kn-affil= affil-num=12 en-affil=Department of Periodontology, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=13 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= en-keyword=Phosphopullulan kn-keyword=Phosphopullulan en-keyword=Polysaccharide kn-keyword=Polysaccharide en-keyword=ADME kn-keyword=ADME en-keyword=Animal study kn-keyword=Animal study en-keyword=Endodontic sealer kn-keyword=Endodontic sealer END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=5 article-no= start-page=257 end-page=267 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=New Catalytic Residues and Catalytic Mechanism of the RNase T1 Family en-subtitle= kn-subtitle= en-abstract= kn-abstract=The ribonuclease T1 family, including RNase Po1 secreted by Pleurotus ostreatus, exhibits antitumor activity. Here, we resolved the Po1/guanosine-3-monophosphate complex (3GMP) structure at 1.75 ?. Structure comparison and fragment molecular orbital (FMO) calculation between the apo form and the Po1/3GMP complex identified Phe38, Phe40, and Glu42 as the key binding residues. Two types of the RNase/3GMP complex in RNasePo1 and RNase T1 were homologous to Po1, and FMO calculations elucidated that the biprotonated histidine on the 3 sheet (His36) on the 3 sheet and deprotonated Glu54 on the 4 sheet were advantageous to RNase activity. Moreover, tyrosine (Tyr34) on the 3 sheet was elucidated as a crucial catalytic residues. Mutation of Tyr34 with phenylalanine decreased RNase activity and diminished antitumor efficacy compared to that in the wild type. This suggests the importance of RNase activity in antitumor mechanisms. en-copyright= kn-copyright= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=HaraYumiko en-aut-sei=Hara en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsutaniTakuya en-aut-sei=Katsutani en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MotoyoshiNaomi en-aut-sei=Motoyoshi en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItagakiTadashi en-aut-sei=Itagaki en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyakawaShuhei en-aut-sei=Miyakawa en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=FukuzawaKaori en-aut-sei=Fukuzawa en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KobayashiHiroko en-aut-sei=Kobayashi en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=3 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=4 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=5 en-affil=School of Pharmacy, Nihon University kn-affil= affil-num=6 en-affil=School of Pharmacy, Nihon University kn-affil= affil-num=7 en-affil=Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=8 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=10 en-affil=School of Pharmacy, Nihon University kn-affil= en-keyword=RNase kn-keyword=RNase en-keyword=crystal structure kn-keyword=crystal structure en-keyword=fragment molecular orbital method kn-keyword=fragment molecular orbital method en-keyword=interfragment interaction energy kn-keyword=interfragment interaction energy en-keyword=antitumor activity kn-keyword=antitumor activity en-keyword=RNase activity kn-keyword=RNase activity END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=3643 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250417 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fully-gapped superconductivity with rotational symmetry breaking in pressurized kagome metal CsV3Sb5 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The discovery of the kagome metal CsV3Sb5 has generated significant interest in its complex physical properties, particularly its superconducting behavior under different pressures, though its nature remains debated. Here, we performed low-temperature, high-pressure 121/123Sb nuclear quadrupole resonance (NQR) measurements to explore the superconducting pairing symmetry in CsV3Sb5. At ambient pressure, we found that the spin-lattice relaxation rate 1/T1 exhibits a kink at T ~ 0.4 Tc within the superconducting state and follows a T3 variation as temperature further decreases. This suggests the presence of two superconducting gaps with line nodes in the smaller one. As pressure increases beyond Pc ~ 1.85?GPa, where the charge-density wave phase is completely suppressed, 1/T1 shows no Hebel-Slichter peak just below Tc, and decreases rapidly, even faster than T5, indicating that the gap is fully opened for pressures above Pc. In this high pressure region, the angular dependence of the in-plane upper critical magnetic field Hc2 breaks the C6 rotational symmetry. We propose the s + id pairing at P > Pc which explains both the 1/T1 and Hc2 behaviors. Our findings indicate that CsV3Sb5 is an unconventional superconductor and its superconducting state is even more exotic at high pressures. en-copyright= kn-copyright= en-aut-name=FengX. Y. en-aut-sei=Feng en-aut-mei=X. Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhaoZ. en-aut-sei=Zhao en-aut-mei=Z. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LuoJ. en-aut-sei=Luo en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhouY. Z. en-aut-sei=Zhou en-aut-mei=Y. Z. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YangJ. en-aut-sei=Yang en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FangA. F. en-aut-sei=Fang en-aut-mei=A. F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YangH. T. en-aut-sei=Yang en-aut-mei=H. T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GaoH.-J. en-aut-sei=Gao en-aut-mei=H.-J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ZhouR. en-aut-sei=Zhou en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ZhengGuo-qing en-aut-sei=Zheng en-aut-mei=Guo-qing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics kn-affil= affil-num=2 en-affil=Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics kn-affil= affil-num=3 en-affil=Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics kn-affil= affil-num=4 en-affil=Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics kn-affil= affil-num=5 en-affil=Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics kn-affil= affil-num=6 en-affil= kn-affil= affil-num=7 en-affil=Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics kn-affil= affil-num=8 en-affil=Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics kn-affil= affil-num=9 en-affil=Institute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter Physics kn-affil= affil-num=10 en-affil=Department of Physics, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=38 article-no= start-page=eadv9952 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250919 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Polymeric microwave rectifiers enabled by monolayer-thick ionized donors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Solution processing of polymeric semiconductors provides a facile way to fabricate functional diodes. However, energy barriers at metal-semiconductor interfaces often limit their performance. Here, we report rectifying polymer diodes with markedly modified energy-level alignments. The gold electrode surface was treated with a dimeric metal complex, which resulted in a shallow work function of 3.7 eV by forming a monolayer-thick ionized donor layer. When a polymeric semiconductor was coated on the treated electrode, most of the ionized donors remained at the metal-semiconductor interface. The confined ionized donors with the ideal thickness enabled fabrication of a polymer diode with a forward current density of over 100 A cm?2. Furthermore, a power conversion efficiency of 7.9% was observed for rectification at a microwave frequency of 920 MHz, which is orders of magnitude higher than that reported for organic diodes. Our findings will pave a way to solution-processed high-frequency and high-power devices. en-copyright= kn-copyright= en-aut-name=OsakabeNobutaka en-aut-sei=Osakabe en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HerJeongeun en-aut-sei=Her en-aut-mei=Jeongeun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanetaTakahiro en-aut-sei=Kaneta en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TajimaAkiko en-aut-sei=Tajima en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LonghiElena en-aut-sei=Longhi en-aut-mei=Elena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TangKan en-aut-sei=Tang en-aut-mei=Kan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujimoriKazuhiro en-aut-sei=Fujimori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BarlowStephen en-aut-sei=Barlow en-aut-mei=Stephen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MarderSeth R. en-aut-sei=Marder en-aut-mei=Seth R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeShun en-aut-sei=Watanabe en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakeyaJun en-aut-sei=Takeya en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamashitaYu en-aut-sei=Yamashita en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=2 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=3 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=4 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology kn-affil= affil-num=6 en-affil=Renewable and Sustainable Energy Institute, University of Colorado Boulder kn-affil= affil-num=7 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology kn-affil= affil-num=9 en-affil=School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology kn-affil= affil-num=10 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=11 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=12 en-affil=Material Innovation Research Center (MIRC) and Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=ycaf092 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Methanol chemoreceptor MtpA- and flagellin protein FliC-dependent methylotaxis contributes to the spatial colonization of PPFM in the phyllosphere en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pink-pigmented facultative methylotrophs (PPFMs) capable of growth on methanol are dominant and versatile phyllosphere bacteria that provide positive effects on plant growth through symbiosis. However, the spatial behavior of PPFMs on plant surfaces and its molecular basis are unknown. Here, we show that Methylobacterium sp. strain OR01 inoculated onto red perilla seeds colonized across the entire plant surface in the phyllosphere concomitant with the plant growth. During its transmission, strain OR01 was found to be present on the entire leaf surface with a preference to sites around the periphery, vein, trichome, and stomata. We found that methanol-sensing chemoreceptor MtpA-dependent chemotaxis (methylotaxis; chemotaxis toward methanol) and flagellin protein FliC-dependent motility facilitated the bacterial entry into the stomatal cavity and their colonization in the phyllosphere. en-copyright= kn-copyright= en-aut-name=KatayamaShiori en-aut-sei=Katayama en-aut-mei=Shiori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiraishiKosuke en-aut-sei=Shiraishi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KajiKanae en-aut-sei=Kaji en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawabataKazuya en-aut-sei=Kawabata en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraNaoki en-aut-sei=Tamura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniAkio en-aut-sei=Tani en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YurimotoHiroya en-aut-sei=Yurimoto en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakaiYasuyoshi en-aut-sei=Sakai en-aut-mei=Yasuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=2 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=3 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Department of Anatomy and Histology, School of Medicine, Fukushima Medical University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=8 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= en-keyword=PPFM kn-keyword=PPFM en-keyword=methylotaxis kn-keyword=methylotaxis en-keyword=phyllosphere kn-keyword=phyllosphere en-keyword=fluorescenceimaging kn-keyword=fluorescenceimaging en-keyword=bacterialbehavior kn-keyword=bacterialbehavior en-keyword=plant-microbeinteraction kn-keyword=plant-microbeinteraction END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=1333 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250816 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phosphorylated pullulan as a local drug delivery matrix for cationic antibacterial chemicals to prevent oral biofilm en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Preventing oral infections, such as oral caries and periodontal disease, helps reduce the risks of various systemic diseases. In this study, the polysaccharide pullulan produced by the black yeast Aureobasidium pullulans was modified in combination with the cationic surfactant cetylpyridinium chloride (CPC) to create a local drug delivery system, and its antibacterial potential on oral bacteria was examined in vitro.
Methods Pullulan was phosphorylated at the CH2OH residue of 6 in the maltotriose structure and mixed with CPC. Bacterial attachment of cariogenic Streptococcus mutans on hydroxyapatite plates (HAPs) treated with the phosphorylated pullulan (PP) and CPC compound (0.01% PP and 0.001? 0.03% CPC, and vice versa) was assessed by observing bacteria using a field emission scanning electron microscope (FE-SEM) and quantified through 16 S rRNA amplification via real-time polymerase chain reaction (PCR). Additionally, the quartz crystal microbalance (QCM) method was employed to evaluate the sustained release of CPC.
Results PP-CPC compound maintained significant bactericidal activity even at 0.01%, which is one-fifth of the conventional applicable concentration of CPC. Additionally, a residual mixture was detected by the hydroxyapatite sensor of the crystal oscillator microbalance detector, suggesting an unknown molecular interaction that enables the sustained release of CPC after attachment to hydroxyapatite.
Conclusions The combination of PP and CPC may contribute to the low concentration and effective prevention of oral infections, such as dental caries. en-copyright= kn-copyright= en-aut-name=Namba-KoideNaoko en-aut-sei=Namba-Koide en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro 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=OkiharaTakumi en-aut-sei=Okihara en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawataYusuke en-aut-sei=Kawata en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoMasahiro en-aut-sei=Ito en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoTakashi en-aut-sei=Ito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Takeuchi-HatanakaKazu en-aut-sei=Takeuchi-Hatanaka en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=3 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, 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 Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Phosphorylated Pullulan kn-keyword=Phosphorylated Pullulan en-keyword=Local drug delivery system kn-keyword=Local drug delivery system en-keyword=Cationic antimicrobial agents kn-keyword=Cationic antimicrobial agents en-keyword=Cetylpyridinium chloride kn-keyword=Cetylpyridinium chloride en-keyword=Oral biofilm kn-keyword=Oral biofilm END start-ver=1.4 cd-journal=joma no-vol=130 cd-vols= no-issue=1 article-no= start-page=e2024JB030704 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reduced Thermal Conductivity of Hydrous Aluminous Silica and Calcium Ferrite]Type Phase Promote Water Transportation to Earth's Deep Mantle en-subtitle= kn-subtitle= en-abstract= kn-abstract=Subduction of oceanic slabs introduces chemical heterogeneities in the Earth's interior, which could further induce thermal, seismic, and geodynamical anomalies. Thermal conductivity of slab minerals crucially controls the thermal evolution and dynamics of the subducted slab and ambient mantle, while such an important transport property remains poorly constrained. Here we have precisely measured high pressure-temperature thermal conductivity of hydrous aluminous post-stishovite (Hy-Al-pSt) and aluminum-rich calcium ferrite-type phase (CF), two important minerals in the subducted basaltic crust in the lower mantle. Compared to the dry aluminous stishovite and pure stishovite, hydration substantially reduces the Hy-Al-pSt, resulting in ?9.7?13.3 W m?1 K?1 throughout the lower mantle. Surprisingly, the CF remains at ?3?3.8 W m?1 K?1 in the lower mantle, few-folds lower than previously assumed. Our data modeling offers better constraints on the thermal conductivity of the subducted oceanic crust from mantle transition zone to the lowermost mantle region, which is less thermally conductive than previously modeled. Our findings suggest that if the post-stishovite carries large amounts of water to the lower mantle, the poorer heat conduction through the basaltic crust reduces the slab's temperature, which not only allows the slab bringing more hydrous minerals to greater depth, but also increases slab's density and viscosity, potentially impacting the stability of heterogeneous structures at the lowermost mantle. en-copyright= kn-copyright= en-aut-name=HsiehWen]Pin en-aut-sei=Hsieh en-aut-mei=Wen]Pin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DeschampsFr?d?ric en-aut-sei=Deschamps en-aut-mei=Fr?d?ric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsaoYi]Chi en-aut-sei=Tsao en-aut-mei=Yi]Chi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChangJen]Wei en-aut-sei=Chang en-aut-mei=Jen]Wei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CrinitiGiacomo en-aut-sei=Criniti en-aut-mei=Giacomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=4 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=5 en-affil=Institute of Earth Sciences, Academia Sinica kn-affil= affil-num=6 en-affil=Earth and Planets Laboratory, Carnegie Institution for Science kn-affil= en-keyword=thermal conductivity kn-keyword=thermal conductivity en-keyword=post-stishovite kn-keyword=post-stishovite en-keyword=calcium ferrite-type phase kn-keyword=calcium ferrite-type phase en-keyword=basaltic crust kn-keyword=basaltic crust END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue=1 article-no= start-page=e70055 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Presence of a Deletion Mutation of Myostatin (MSTN) Gene Associated With Double-Muscling Phenotype in Japanese Black Cattle Population en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mutations in the bovine myostatin (MSTN) gene have been identified as the causative factor for the double-muscling phenotype in several European cattle breeds, including Belgian Blue, Piedmontese, and Shorthorn. In Japan, following the Meiji Restoration, several European breeds, including Shorthorn, Brown Swiss, Devon, Simmental, and Ayrshire, were introduced and crossbred with native cattle to develop modern Japanese beef cattle breeds, such as Japanese Black cattle. Historical records regarding the breeding of Japanese Black cattle indicate that the double-muscling phenotype, referred to as gButajiri,h occasionally appeared in Japanese Black cattle population. These historical observations suggest the potential presence of MSTN gene mutation in the Japanese Black cattle population. The aim of this study was, therefore, to investigate the presence of MSTN gene mutation in the current Japanese Black cattle population. Through screening 400 reproductive females, we identified one cow carrying an 11-bp deletion in the MSTN gene. While further investigation of the animals in the pedigree of this cow could not reveal any living animals with this mutation, this is the first report demonstrating the presence of the MSTN mutation in the Japanese Black cattle population. en-copyright= kn-copyright= en-aut-name=LeNu?Anh?Thu en-aut-sei=Le en-aut-mei=Nu?Anh?Thu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuboRena en-aut-sei=Kubo en-aut-mei=Rena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BorjiginLiushiqi en-aut-sei=Borjigin en-aut-mei=Liushiqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IbiTakayuki en-aut-sei=Ibi en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasakiShinji en-aut-sei=Sasaki en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuniedaTetsuo en-aut-sei=Kunieda en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Faculty of Veterinary Medicine Okayama University of Science Imabari kn-affil= affil-num=2 en-affil=Faculty of Veterinary Medicine Okayama University of Science Imabari kn-affil= affil-num=3 en-affil=Faculty of Veterinary Medicine Okayama University of Science Imabari kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Agriculture Ryukyu University Nishihara kn-affil= affil-num=6 en-affil=Faculty of Veterinary Medicine Okayama University of Science Imabari kn-affil= en-keyword=double muscle kn-keyword=double muscle en-keyword=Japanese Black cattle kn-keyword=Japanese Black cattle en-keyword=myostatin gene kn-keyword=myostatin gene END start-ver=1.4 cd-journal=joma no-vol=142 cd-vols= no-issue= article-no= start-page=104967 end-page= 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=Cross-feeding between beneficial and pathogenic bacteria to utilize eukaryotic host cell-derived sialic acids and bacteriophages shape the pathogen-host interface milieu en-subtitle= kn-subtitle= en-abstract= kn-abstract=Under an inflamed-intestinal milieu, increased free sialic acids are associated with the overgrowth of some pathogenic bacterial strains. Recently, the protective immunomodulatory activity of gut bacteriophages (phages) has also been highlighted. However, the role of phages in triple reciprocal interactions between pathogenic bacteria, beneficial bacteria, and their host cell sialic acids has not been studied so far. We established a sialidase-explicit model in which beneficial and pathogenic bacteria interact through cross-feeding and competition for free sialic acid using a human triple co-culture cell model incorporating colonocytes (T84 cells), monocytes (THP-1 cells), and hepatocytes (Huh7 cells). Triple co-cultured cells were challenged with Gram-positive Bifidobacterium bifidum (B. bifidum) and Gram-negative Pseudomonas aeruginosa PAO1 (P. a PAO1) in the absence or presence of its KPP22 phage in two different cell culture mediums: 1) standard Dulbecco's Modified Eagle Medium (DMEM) and 2) DMEM with 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). Changes in physiological, functional, and structural health markers of stimulated cocultured cells were evaluated. The concentrations of sialic acid and pro-inflammatory cytokines in the cell culture supernatants were quantified. P. a PAO1 triggered the release of interleukin 6 and 8 (IL-6 and IL-8), accompanied by increased levels of free sialic acid, reduced viability of co-cultured cells, and disrupted the integrity of the cellular monolayer. These disruptive effects were markedly attenuated by KPP22 phage and B. bifidum. In addition to well-documented differences in the structure and composition of the bacterial cell walls of Gram-negative pathogenic bacteria and bifidobacteria, two distinct factors seem to be pivotal in modulating the pathogen-host interface milieu: (i) the presence of phages and (ii) the utilization of free sialic acids secreted from host cells by bifidobacteria. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=F?lster-HolstRegina en-aut-sei=F?lster-Holst en-aut-mei=Regina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Bl?merSophia en-aut-sei=Bl?mer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EbsenMichael en-aut-sei=Ebsen en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=R?ckenChristoph en-aut-sei=R?cken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BockelmannWilhelm en-aut-sei=Bockelmann en-aut-mei=Wilhelm kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= affil-num=2 en-affil=Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein kn-affil= affil-num=3 en-affil=Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein kn-affil= affil-num=4 en-affil=St?dtisches MVZ Kiel GmbH (Kiel City Hospital), Department of Pathology kn-affil= affil-num=5 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=6 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=8 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= en-keyword=Bacterial sialidase kn-keyword=Bacterial sialidase en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Cytokines kn-keyword=Cytokines en-keyword=Infection kn-keyword=Infection en-keyword=Bifidobacteria kn-keyword=Bifidobacteria en-keyword=Phages kn-keyword=Phages END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=35 article-no= start-page=28887 end-page=28895 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=Thermally polymerizable phthalocyanine realizes a metal?nitrogen-doped carbon material featuring a defined single-atom catalyst motif with CO2RR activity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metal?nitrogen-doped carbon materials (MNCs) exhibit good electrocatalytic performance owing to the intrinsic advantages of carbon-based materials and the presence of isolated and stabilized metal atoms coordinated by nitrogen sites. However, conventional high-temperature pyrolysis of precursor molecules make it difficult to control the coordination structure precisely. To address this issue, here we report a new synthesis strategy for MNCs. Specifically, we design and synthesize Ni-phthalocyanine functionalized with ethynyl groups as solid-state thermal polymerization points. After depositing the Ni-phthalocyanine precursor on a carbon support and performing a thermal treatment, the resultant carbon composite material features a Ni?N4 coordination structure derived from the precursor, and enhanced porosity. This material demonstrates high catalytic activity for the CO2 reduction reaction (CO2RR). Our synthetic approach is applicable to various precursor molecules and carbon supports, paving the way for the further development of MNC-based electrode catalysts. en-copyright= kn-copyright= en-aut-name=SanoYuki en-aut-sei=Sano en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaDaichi en-aut-sei=Nakajima en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MannaBiplab en-aut-sei=Manna en-aut-mei=Biplab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChidaKoki en-aut-sei=Chida en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyodaRyojun en-aut-sei=Toyoda en-aut-mei=Ryojun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakaishiShinya en-aut-sei=Takaishi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwaseKazuyuki en-aut-sei=Iwase en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaranoKoji en-aut-sei=Harano en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshiiTakeharu en-aut-sei=Yoshii en-aut-mei=Takeharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakamotoRyota en-aut-sei=Sakamoto en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= affil-num=2 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= affil-num=3 en-affil=Center for Basic Research on Materials, National Institute for Materials Science kn-affil= affil-num=4 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= affil-num=6 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= affil-num=7 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=8 en-affil=Center for Basic Research on Materials, National Institute for Materials Science kn-affil= affil-num=9 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=11 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=4 article-no= start-page=045010 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250911 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Covalent cross-linked graphene oxide aerogels for moisture adsorption en-subtitle= kn-subtitle= en-abstract= kn-abstract=Covalent cross-linking is an effective approach to enhance the hydrophilicity and water adsorption properties of graphene oxide (GO). We studied moisture absorption in GO cross-linked with poly(ethylene glycol) diamines. At relative humidity (RH) of 85%, the PEG-cross-linked GO exhibited a significantly enhanced water uptake capacity of 0.59 g of water per gram of GO (gg?1), compared to 0.37 for unmodified GO. This is attributed to the presence of alkoxy groups via cross-linking, resulting in the enhanced interaction between GO and water molecules. These findings highlight the potential of PEG-based covalent functionalisation for efficient moisture capture in GO-based materials. en-copyright= kn-copyright= en-aut-name=CaoZhijian en-aut-sei=Cao en-aut-mei=Zhijian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RenXiaojun en-aut-sei=Ren en-aut-mei=Xiaojun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LinTongxi en-aut-sei=Lin en-aut-mei=Tongxi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimuraMasamichi en-aut-sei=Yoshimura en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JoshiRakesh en-aut-sei=Joshi en-aut-mei=Rakesh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=School of Materials Science and Engineering, University of New South Wales kn-affil= affil-num=2 en-affil=School of Materials Science and Engineering, University of New South Wales kn-affil= affil-num=3 en-affil=School of Materials Science and Engineering, University of New South Wales kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Engineering, Toyota Technological Institute kn-affil= affil-num=6 en-affil=School of Materials Science and Engineering, University of New South Wales kn-affil= en-keyword=graphene oxide (GO) kn-keyword=graphene oxide (GO) en-keyword=covalent cross-linking kn-keyword=covalent cross-linking en-keyword=poly(ethylene glycol) (PEG) kn-keyword=poly(ethylene glycol) (PEG) en-keyword=moisture adsorption kn-keyword=moisture adsorption en-keyword=hydrophilicity enhancement kn-keyword=hydrophilicity enhancement END