start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=4175 end-page= 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=Structure of a photosystem II-FCPII supercomplex from a haptophyte reveals a distinct antenna organization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Haptophytes are unicellular algae that produce 30 to 50% of biomass in oceans. Among haptophytes, a subset named coccolithophores is characterized by calcified scales. Despite the importance of coccolithophores in global carbon fixation and CaCO3 production, their energy conversion system is still poorly known. Here we report a cryo-electron microscopic structure of photosystem II (PSII)-fucoxanthin chlorophyll c-binding protein (FCPII) supercomplex from Chyrostila roscoffensis, a representative of coccolithophores. This complex has two sets of six dimeric and monomeric FCPIIs, with distinct orientations. Interfaces of both FCPII/FCPII and FCPII/core differ from previously reported. We also determine the sequence of Psb36, a subunit previously found in diatoms and red algae. The principal excitation energy transfer (EET) pathways involve mainly 5 FCPIIs, where one FCPII monomer mediates EET to CP47. Our findings provide a solid structural basis for EET and energy dissipation pathways occurring in coccolithophores. en-copyright= kn-copyright= en-aut-name=La RoccaRomain en-aut-sei=La Rocca en-aut-mei=Romain kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TsaiPi-Cheng en-aut-sei=Tsai en-aut-mei=Pi-Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkitaFusamichi en-aut-sei=Akita en-aut-mei=Fusamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, and Advanced Research Field, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=3 article-no= start-page=459 end-page=470 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250326 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Text mining for case report articles on “peritoneal dialysis” from PubMed database en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: The number of published medical articles on peritoneal dialysis (PD) has been increasing, and efficiently selecting information from numerous articles can be difficult. In this study, we examined whether artificial intelligence (AI) text mining can be a good support for efficiently collecting PD information.
Methods: We performed text mining and analyzed all the abstracts of case reports on PD in the PubMed database. In total, 3137 case reports with abstracts related to “peritoneal dialysis” published from 1970 to 2021 were identified.
Results: A total of 280?347 relevant words were extracted from all the abstracts. Word frequency analysis, word dependency analysis, and word frequency transition analysis showed that peritonitis, encapsulating peritoneal sclerosis, and child have been important keywords. Theseanalyses not only reflected historical background but also anticipated future trends of PD study.
Conclusion: These suggest that text mining can be a good support for efficiently collecting PD information. en-copyright= kn-copyright= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko 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=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki 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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=case reports kn-keyword=case reports en-keyword=peritoneal dialysis kn-keyword=peritoneal dialysis en-keyword=text mining kn-keyword=text mining 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=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Supplement-induced acute kidney injury reproduced in kidney organoids en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Acute kidney injury associated with the consumption of Beni-koji CholesteHelp supplements, which contain red yeast rice (Beni-Koji), has become a significant public health concern in Japan. While renal biopsy findings from several case reports have suggested tubular damage, no definitive causal relationship has been established, and the underlying mechanisms of kidney injury remain poorly understood. The complexity of identifying toxic substances in supplements containing various bioactive compounds makes conventional investigative approaches both time-consuming and challenging. This highlights an urgent need to establish a reliable platform for assessing organ-specific toxicity in such supplements. In this study, we utilized a kidney organoid model derived from adult rat kidney stem cells (KS cells) to assess the potential tubular toxicity of these supplements. Methods: KS cell clusters were cultured in three-dimensional system supplemented with growth factors to promote kidney organoids. The organoids were subsequently exposed to Beni-koji CholesteHelp supplements or cisplatin, followed by histological and molecular analyses to evaluate structural impacts. Results: Established organoids had the kidney-like structures including tubular-like structures and glomerulus-like structures at the tips of multiple tubules. Treatment with Beni-koji CholesteHelp supplements induced significant tubular damage in the organoids, characterized by epithelial cell thinning, structural disruption, and increase in cleaved-caspase 3-positive apoptotic tubular cells, similar to the organoids treated with cisplatin. Conclusion: These findings provide the first evidence suggesting that certain toxicants in specific batches of Beni-koji CholesteHelp supplements cause direct renal tubular injury. This KS cell-based organoid system represents a cost-effective, reproducible, and technically simple platform for nephrotoxicity screening. 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=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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 Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Acute kidney injury kn-keyword=Acute kidney injury en-keyword=Drug-induced nephrotoxicity kn-keyword=Drug-induced nephrotoxicity en-keyword=Kidney organoid kn-keyword=Kidney organoid en-keyword=Kidney stem cell kn-keyword=Kidney stem cell 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=20250501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Xenopus laevis as an infection model for human pathogenic bacteria en-subtitle= kn-subtitle= en-abstract= kn-abstract=Animal infection models are essential for understanding bacterial pathogenicity and corresponding host immune responses. In this study, we investigated whether juvenile Xenopus laevis could be used as an infection model for human pathogenic bacteria. Xenopus frogs succumbed to intraperitoneal injection containing the human pathogenic bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Listeria monocytogenes. In contrast, non-pathogenic bacteria Bacillus subtilis and Escherichia coli did not induce mortality in Xenopus frogs. The administration of appropriate antibiotics suppressed mortality caused by S. aureus and P. aeruginosa. Strains lacking the agr locus, cvfA (rny) gene, or hemolysin genes in S. aureus, LIPI-1-deleted mutant of L. monocytogenes, which attenuate virulence within mammals, exhibited reduced virulence in Xenopus frogs compared with their respective wild-type counterparts. Bacterial distribution analysis revealed that S. aureus persisted in the blood, liver, heart, and muscles of Xenopus frogs until death. These results suggested that intraperitoneal injection of human pathogenic bacteria induces sepsis-like symptoms in Xenopus frogs, supporting their use as a valuable animal model for evaluating antimicrobial efficacy and identifying virulence genes in various human pathogenic bacteria. en-copyright= kn-copyright= en-aut-name=KuriuAyano en-aut-sei=Kuriu en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchiyaKohsuke en-aut-sei=Tsuchiya en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Immunology and Molecular Biology, Cancer Research Institute, Kanazawa University kn-affil= affil-num=4 en-affil=Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Molecular Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=animal infection model kn-keyword=animal infection model en-keyword=Staphylococcus aureus kn-keyword=Staphylococcus aureus en-keyword=Listeria monocytogenes kn-keyword=Listeria monocytogenes en-keyword=Pseudomonas aeruginosa kn-keyword=Pseudomonas aeruginosa en-keyword=antibiotics efficacy kn-keyword=antibiotics efficacy en-keyword=virulence genes kn-keyword=virulence genes en-keyword=hemolysin kn-keyword=hemolysin END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=5 article-no= start-page=e70087 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic Islands of Pseudomonas syringae pv. tabaci 6605: Identification of PtaGI-1 as a Pathogenicity Island With Effector Genes and a Tabtoxin Cluster en-subtitle= kn-subtitle= en-abstract= kn-abstract=Genomic islands (GIs) are 20-500 kb DNA regions that are thought to be acquired by horizontal gene transfer. GIs that confer pathogenicity and environmental adaptation have been reported in Pseudomonas species; however, GIs that enhance bacterial virulence have not. Here, we identified 110 kb and 103 kb GIs in P. syringae pv. tabaci 6605 (Pta6605), the causative agent of tobacco wildfire disease, which has the ability to produce tabtoxin as a phytotoxin. These GIs are partially homologous to known genomic islands in Pseudomonas aeruginosa and P. syringae pv. phaseolicola and were designated PtaGI-1 and PtaGI-2. Both PtaGIs conserve core genes, whereas each GI possesses different accessory genes. PtaGI-1 contains a tabtoxin biosynthetic gene cluster and three type III effector genes among its accessory genes, whereas PtaGI-2 also contains homologous genes to hsvABC, pathogenicity-related genes in Erwinia amylovora. Inoculation revealed that the PtaGI-1 mutant, but not the PtaGI-2 mutant, lost the ability to biosynthesise tabtoxin and to cause disease. Therefore, PtaGI-1 is thought to be a pathogenicity island. Both PtaGI-1 and PtaGI-2 have a pseudogene of tRNALys on the left border and an intact tRNALys gene on the right border. In a colony of Pta6605, both GIs can be excised at tRNALys, and PtaGI-1 and PtaGI-2 exist in a circular form. These results indicate that tabtoxin biosynthesis genes in PtaGI-1 are required for disease development, and PtaGI-1 is necessary for Pta6605 virulence. en-copyright= kn-copyright= en-aut-name=WatanabeYuta en-aut-sei=Watanabe en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KunishiKotomi en-aut-sei=Kunishi en-aut-mei=Kotomi 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=Faculty of Agriculture,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=horizontal gene transfer kn-keyword=horizontal gene transfer en-keyword=integrative and conjugative elements kn-keyword=integrative and conjugative elements en-keyword=pathogenicity island kn-keyword=pathogenicity island en-keyword=Pseudomonas syringae kn-keyword=Pseudomonas syringae en-keyword=tabtoxin kn-keyword=tabtoxin END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=6 article-no= start-page=97 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of aged garlic extract on experimental periodontitis in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aged garlic extract (AGE) has been reported to exert anti?inflammatory effects. AGE has been recently found to reduce the inflammatory symptoms of periodontitis, a widespread chronic inflammatory disease caused by oral bacterial infection. However, the mechanisms underlying these effects remain unclear. In the present study, it was aimed to determine the effects of AGE on experimental periodontitis and the related inflammatory factors. AGE (2 g/kg/day) was orally administered to 15 mice during the experimental period, while a control group consisted of 15 mice that received pure water. A total of 3 days after initiation of administration, the left maxillary second molar was ligated with a 5?0 silk thread for 7 days. Blood biochemical tests were performed to monitor the systemic effects of AGE. Alveolar bone loss was measured morphometrically using a stereomicroscope, and reverse transcription?quantitative PCR was performed to assay mRNAs of proinflammatory cytokines in gingival tissues. A histological survey was also performed to identify osteoclasts in periodontitis lesions (five mice per group). The total protein and albumin levels showed no significant differences between the AGE and control groups. However, ligation?induced bone resorption was lower in the AGE group than in the control group (P=0.01). Additionally, ligature increased the mRNA expression of inflammatory cytokines, whereas AGE administration tended to suppress them. Remarkably, tumor necrosis factor gene expression was significantly suppressed (P=0.04). The number of osteoclasts in periodontitis lesions was reduced in the AGE?treated group. These results indicate that AGE prevents alveolar bone loss by suppressing the inflammatory responses related to osteoclast differentiation in the periodontal tissue. Further research is needed to elucidate the role of AGE in reducing inflammatory bone resorption. en-copyright= kn-copyright= en-aut-name=KuangCanyan en-aut-sei=Kuang en-aut-mei=Canyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraiAnna en-aut-sei=Hirai en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Kamei?ΝagataChiaki en-aut-sei=Kamei?Νagata en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NangoHiroshi en-aut-sei=Nango en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtaniMasahiro en-aut-sei=Ohtani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Central Research Institute, Wakunaga Pharmaceutical Co., Ltd. kn-affil= affil-num=5 en-affil=Central Research Institute, Wakunaga Pharmaceutical Co., Ltd. kn-affil= affil-num=6 en-affil=Department of Pathophysiology?Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathophysiology?Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=AGE kn-keyword=AGE en-keyword=experimental periodontitis kn-keyword=experimental periodontitis en-keyword=bone resorption kn-keyword=bone resorption en-keyword=inflammation kn-keyword=inflammation en-keyword=osteoclasts kn-keyword=osteoclasts END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative inhibitory effects of bepotastine and diphenhydramine on rituximab-induced infusion reactions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Infusion-related reaction (IRR) is a common adverse event induced by rituximab. Although first-generation histamine 1 receptor antagonists (H1RAs) are commonly used to prevent IRR, evidence on IRR suppression by the second-generation H1RA bepotastine is scarce. In this study, we assessed the inhibitory effects of bepotastine on rituximab-induced IRR and compared them with those of the first-generation H1RA diphenhydramine.
Methods We retrospectively evaluated IRR incidence in patients with B-cell non-Hodgkin lymphoma who received their first dose of rituximab.
Results The incidence of any grade IRR was 9.8% in the bepotastine group (n?=?92), which was significantly lower than the 30.2% rate in the diphenhydramine group (n?=?96; p? Conclusion Bepotastine may be more effective than diphenhydramine in reducing the incidence of rituximab-induced IRR, particularly low-grade reactions. en-copyright= kn-copyright= en-aut-name=HoriTomoki en-aut-sei=Hori en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakagawaTomoaki en-aut-sei=Nakagawa en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakagawaRinako en-aut-sei=Nakagawa en-aut-mei=Rinako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkayamaMasami en-aut-sei=Okayama en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SudouTamika en-aut-sei=Sudou en-aut-mei=Tamika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamasakiMoe en-aut-sei=Hamasaki en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YasudaMai en-aut-sei=Yasuda en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiShinya en-aut-sei=Kobayashi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraFumihiko en-aut-sei=Nakamura en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YagiHideo en-aut-sei=Yagi en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IkushimaShigeki en-aut-sei=Ikushima en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YanoIkuko en-aut-sei=Yano en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=2 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=4 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=5 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=6 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=7 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=8 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Nara Prefecture General Medical Center kn-affil= affil-num=10 en-affil=Department of Laboratory Medicine, Nara Prefecture General Medical Center kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Nara Prefecture General Medical Center kn-affil= affil-num=12 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=13 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=14 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=Rituximab kn-keyword=Rituximab en-keyword=Infusion reaction kn-keyword=Infusion reaction en-keyword=Bepotastine kn-keyword=Bepotastine en-keyword=Diphenhydramine kn-keyword=Diphenhydramine END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=7 article-no= start-page=193 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Osteosarcoma cell-derived CCL2 facilitates lung metastasis via accumulation of tumor-associated macrophages en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteosarcoma (OS) is the most common malignant tumor of bone in children and adolescents. Although lung metastasis is a major obstacle to improving the prognosis of OS patients, the underlying mechanism of lung metastasis of OS is poorly understood. Tumor-associated macrophages (TAMs) with M2-like characteristics are reportedly associated with lung metastasis and poor prognosis in OS patients. In this study, we investigated the metastasis-associated tumor microenvironment (TME) in orthotopic OS tumor models with non-metastatic and metastatic OS cells. Non-metastatic and metastatic tumor cells derived from mouse OS (Dunn and LM8) and human OS (HOS and 143B) were used to analyze the TME associated with lung metastasis in orthotopic OS tumor models. OS cell-derived secretion factors were identified by cytokine array and enzyme-linked immunosorbent assay (ELISA). Orthotopic tumor models with metastatic LM8 and 143B cells were analyzed to evaluate the therapeutic potential of a neutralizing antibody in the development of primary and metastatic tumors. Metastatic OS cells developed metastatic tumors with infiltration of M2-like TAMs in the lungs. Cytokine array and ELISA demonstrated that metastatic mouse and human OS cells commonly secreted CCL2, which was partially encapsulated in extracellular vesicles. In vivo experiments demonstrated that while primary tumor growth was unaffected, administration of CCL2-neutralizing antibody led to a significant suppression of lung metastasis and infiltration of M2-like TAMs in the lung tissue. Our results suggest that CCL2 plays a crucial role in promoting the lung metastasis of OS cells via accumulation of M2-like TAMs. en-copyright= kn-copyright= en-aut-name=KondoHiroya en-aut-sei=Kondo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KureMiho en-aut-sei=Kure en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DemiyaKoji en-aut-sei=Demiya en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HataToshiaki en-aut-sei=Hata en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshiokaYusuke en-aut-sei=Yoshioka en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Molecular and Cellular Medicine, Tokyo Medical University kn-affil= affil-num=14 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Osteosarcoma kn-keyword=Osteosarcoma en-keyword=Lung metastasis kn-keyword=Lung metastasis en-keyword=Tumor-associated macrophage kn-keyword=Tumor-associated macrophage en-keyword=CCL2 kn-keyword=CCL2 en-keyword=Extracellular vesicle kn-keyword=Extracellular vesicle END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page=1559 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Oral squamous cell carcinoma (OSCC) frequently invades the jawbone, leading to diagnostic and therapeutic challenges. While tumor-bone interactions have been studied, the specific roles of dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) in OSCC-associated bone resorption remain unclear. This study aimed to compare the effects of DFCs and PDLCs on OSCC-induced bone invasion and elucidate the underlying mechanisms. Methods: Primary human DFCs and PDLCs were isolated from extracted third molars and characterized by Giemsa and immunofluorescence staining. An in vitro co-culture system and an in vivo xenograft mouse model were established using the HSC-2 OSCC cell line. Tumor invasion and osteoclast activation were assessed by hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining. Immunohistochemical analysis was performed to evaluate the expression of receptor activator of NF-kappa B ligand (RANKL) and parathyroid hormone-related peptide (PTHrP). Results: DFCs significantly enhanced OSCC-induced bone resorption by promoting osteoclastogenesis and upregulating RANKL and PTHrP expression. In contrast, PDLCs suppressed RANKL expression and partially modulated PTHrP levels, thereby reducing osteoclast activity. Conclusions: DFCs and PDLCs exert opposite regulatory effects on OSCC-associated bone destruction. These findings underscore the importance of stromal heterogeneity and highlight the therapeutic potential of targeting specific stromal-tumor interactions to mitigate bone-invasive OSCC. en-copyright= kn-copyright= en-aut-name=ChangAnqi en-aut-sei=Chang en-aut-mei=Anqi 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=PiaoTianyan en-aut-sei=Piao en-aut-mei=Tianyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=dental follicle cells kn-keyword=dental follicle cells en-keyword=periodontal ligament cells kn-keyword=periodontal ligament cells en-keyword=bone invasion kn-keyword=bone invasion en-keyword=receptor activator of NF-kappa B ligand kn-keyword=receptor activator of NF-kappa B ligand en-keyword=parathyroid hormone-related peptide kn-keyword=parathyroid hormone-related peptide END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=7 article-no= start-page=192 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Recent studies have revealed that CD8+ T cells can be activated via genetic upregulation of HIF-1 alpha, thereby augmenting antitumor effector functions. HIF-1 alpha upregulation can be attained by inhibiting HIF-prolyl hydroxylase (HIF-PH) under normoxic conditions, termed pseudohypoxia. This study investigated whether pseudohypoxia induced by HIF-PH inhibitors suppresses Microsatellite stable (MSS) colorectal cancer (CRC) by affecting tumor immune response.
Methods The HIF-PH inhibitors Roxadustat and Vadadustat were utilized in this study. In vitro, we assessed the effects of HIF-PH inhibitors on human and murine colon cancer cell lines (SW480, HT29, Colon26) and murine T cells. In vivo experiments were performed with mice bearing Colon26 tumors to evaluate the effect of these inhibitors on tumor immune responses. Tumor and spleen samples were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry to elucidate potential mechanisms.
Results HIF-PH inhibitors demonstrated antitumor effects in vivo but not in vitro. These inhibitors enhanced the tumor immune response by increasing the infiltration of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs). HIF-PH inhibitors induced IL-2 production in splenic and intratumoral CD4+ T cells, promoting T cell proliferation, differentiation, and immune responses. Roxadustat synergistically enhanced the efficacy of anti-PD-1 antibody for MSS cancer by increasing the recruitment of TILs and augmenting effector-like CD8+ T cells.
Conclusion Pseudohypoxia induced by HIF-PH inhibitors activates antitumor immune responses, at least in part, through the induction of IL-2 secretion from CD4+ T cells in the spleen and tumor microenvironment, thereby enhancing immune efficacy against MSS CRC. en-copyright= kn-copyright= en-aut-name=ChenYuehua en-aut-sei=Chen en-aut-mei=Yuehua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaYusuke en-aut-sei=Hamada en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangYuze en-aut-sei=Wang en-aut-mei=Yuze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TianMiao en-aut-sei=Tian en-aut-mei=Miao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Colorectal cancer kn-keyword=Colorectal cancer en-keyword=Microsatellite stable kn-keyword=Microsatellite stable en-keyword=Hypoxia-inducible factor kn-keyword=Hypoxia-inducible factor en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=1 article-no= start-page=715 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=TRPV2 mediates stress resilience in mouse cardiomyocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=The heart dynamically compensates for haemodynamic stress, but how this resilience forms during cardiac growth is not clear. Using a temporally inducible, cardiac-specific knockout in mice we show that the Transient receptor potential vanilloid family 2 (TRPV2) channel is crucial for the maturation of cardiomyocyte stress resilience. TRPV2 defects in growing hearts lead to small morphology, abnormal intercalated discs, weak contractility, and low expression of serum response factor and Insulin-like growth factor-1 (IGF-1) signalling. Individual cardiomyocytes of TRPV2-deficient hearts show reduced contractility with abnormal Ca2+ handling. In cultured neonatal cardiomyocytes, mechanical Ca2+ response, excitation-contraction coupling, sarcoplasmic reticulum Ca2+ content, actin formation, nuclear localisation of Myocyte enhancer factor 2c, and IGF-1 expression require TRPV2. TRPV2-deficient hearts show a defective response to dobutamine stress and no compensatory hypertrophic response to phenylephrine administration, but no stress response to pressure overload. These data suggest TRPV2 mediates the maturation of cardiomyocyte stress resilience, and will advance therapeutic interventions and drug discovery for heart disease. en-copyright= kn-copyright= en-aut-name=DongYubing en-aut-sei=Dong en-aut-mei=Yubing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangGuohao en-aut-sei=Wang en-aut-mei=Guohao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UjiharaYoshihiro en-aut-sei=Ujihara en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChenYanzhu en-aut-sei=Chen en-aut-mei=Yanzhu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatanosakaKimiaki en-aut-sei=Katanosaka en-aut-mei=Kimiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Electrical and Mechanical Engineering, Graduate School of Engineering, Nagoya Institute of Technology kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University kn-affil= affil-num=8 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=5 article-no= start-page=e70091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pseudomonas syringae pv. tabaci 6605 Requires Seven Type III Effectors to Infect Nicotiana benthamiana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Type III effectors (T3Es), virulence factors injected into plant cells via the type III secretion system (T3SS), play essential roles in the infection of host plants. Pseudomonas syringae pv. tabaci 6605 (Pta 6605) is the causal agent of wildfire disease in tobacco and harbours at least 22 T3Es in its genome. However, the specific T3Es required by Pta 6605 to infect Nicotiana benthamiana remain unidentified. In this study, we investigated the T3Es that contribute to Pta 6605 infection of N. benthamiana. We constructed Pta 6605 poly-T3E-deficient mutants (Pta DxE) and inoculated them into N. benthamiana. Flood assay, which mimics natural opening-based entry, showed that mutant strains lacking 14-22 T3Es, namely, Pta D14E-D22E mutants, exhibited reduced disease symptoms. By contrast, infiltration inoculation, which involves direct injection into leaves, showed that the Pta D14E to Pta D20E mutants developed disease symptoms. Notably, the Pta D20E, containing AvrE1 and HopM1, induced weak but observable symptoms upon infiltration inoculation. Conversely, no symptoms were observed in either the flood assay or infiltration inoculation for Pta D21E and Pta D22E. Taken together, these findings indicate that the many T3Es such as AvrPto4/AvrPtoB, HopW1/HopAE1, and HopM1/AvrE1 in Pta 6605 collectively contribute to invasion through natural openings and symptom development in N. benthamiana. This study provides the basis for understanding virulence in the host by identifying the minimum T3E repertoire required by Pta 6605 to infect N. benthamiana. en-copyright= kn-copyright= en-aut-name=KuroeKana en-aut-sei=Kuroe en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KashiharaSachi en-aut-sei=Kashihara en-aut-mei=Sachi 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=YamamotoMikihiro en-aut-sei=Yamamoto en-aut-mei=Mikihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=poly T3E mutant kn-keyword=poly T3E mutant en-keyword=type III effector kn-keyword=type III effector en-keyword=type III secretion system kn-keyword=type III secretion system END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=4 article-no= start-page=043024 end-page= 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=Characterization of the thorium-229 defect structure in CaF2 crystals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent advancements in laser excitation of the low-energy thorium-229 (229Th) nuclear isomeric state in calcium fluoride (CaF2) single crystals render this system a promising candidate for a solid-state nuclear clock. Nonetheless, the precise experimental determination of the microscopic ion configuration surrounding the doped 229Th and its electronic charge state remains a critical challenge. Such characterization is essential for precisely controlling the clock transition and evaluating the performance of this solid-state nuclear clock system. In this study, we use x-ray absorption fine structure spectroscopy of 229Th:CaF2 to investigate the charge state and coordination environment of doped 229Th. The results indicate that 229Th displays a 4+ oxidation state at the substitutional site of a Ca2+ ion, with charge compensated provided by two F? ions positioned at interstitial sites adjacent to 229Th. en-copyright= kn-copyright= en-aut-name=TakatoriS. en-aut-sei=Takatori en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PimonM. en-aut-sei=Pimon en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PollittS. en-aut-sei=Pollitt en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BartokosM. en-aut-sei=Bartokos en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BeeksK. en-aut-sei=Beeks en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GrueneisA. en-aut-sei=Grueneis en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HirakiT. en-aut-sei=Hiraki en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HonmaT. en-aut-sei=Honma en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HosseiniN. en-aut-sei=Hosseini en-aut-mei=N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LeitnerA. en-aut-sei=Leitner en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasudaT. en-aut-sei=Masuda en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MorawetzI en-aut-sei=Morawetz en-aut-mei=I kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NittaK. en-aut-sei=Nitta en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkaiK. en-aut-sei=Okai en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=RiebnerT. en-aut-sei=Riebner en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SchadenF. en-aut-sei=Schaden en-aut-mei=F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SchummT. en-aut-sei=Schumm en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SekizawaO. en-aut-sei=Sekizawa en-aut-mei=O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SikorskyT. en-aut-sei=Sikorsky en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakahashiY. en-aut-sei=Takahashi en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=De ColCol, L. Toscani en-aut-sei=De Col en-aut-mei=Col, L. Toscani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YamamotoR. en-aut-sei=Yamamoto en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YomogidaT. en-aut-sei=Yomogida en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=YoshimiA. en-aut-sei=Yoshimi en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshimuraK. en-aut-sei=Yoshimura en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science (RIIS), Okayama University kn-affil= affil-num=2 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=3 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=4 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=5 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=6 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science (RIIS), Okayama University kn-affil= affil-num=8 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=9 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=10 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=11 en-affil=Research Institute for Interdisciplinary Science (RIIS), Okayama University kn-affil= affil-num=12 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=13 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=14 en-affil=Research Institute for Interdisciplinary Science (RIIS), Okayama University kn-affil= affil-num=15 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=16 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=17 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=18 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=19 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=20 en-affil=Department of Earth and Planetary Science, The University of Tokyo kn-affil= affil-num=21 en-affil=Faculty of Physics, TU Wien kn-affil= affil-num=22 en-affil=Research Institute for Interdisciplinary Science (RIIS), Okayama University kn-affil= affil-num=23 en-affil=Department of Earth and Planetary Science, The University of Tokyo kn-affil= affil-num=24 en-affil=Research Institute for Interdisciplinary Science (RIIS), Okayama University kn-affil= affil-num=25 en-affil=Research Institute for Interdisciplinary Science (RIIS), Okayama University kn-affil= en-keyword=solid-state nuclear clock kn-keyword=solid-state nuclear clock en-keyword=thorium-229 kn-keyword=thorium-229 en-keyword=XAFS kn-keyword=XAFS END start-ver=1.4 cd-journal=joma no-vol=116 cd-vols= no-issue=5 article-no= start-page=1214 end-page=1226 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High Antigenicity for Treg Cells Confers Resistance to PD-1 Blockade Therapy via High PD-1 Expression in Treg Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Regulatory T (Treg) cells have an immunosuppressive function, and programmed death-1 (PD-1)-expressing Treg cells reportedly induce resistance to PD-1 blockade therapies through their reactivation. However, the effects of antigenicity on PD-1 expression in Treg cells and the resistance to PD-1 blockade therapy remain unclear. Here, we show that Treg cells gain high PD-1 expression through an antigen with high antigenicity. Additionally, tumors with high antigenicity for Treg cells were resistant to PD-1 blockade in vivo due to PD-1+ Treg-cell infiltration. Because such PD-1+ Treg cells have high cytotoxic T lymphocyte antigen (CTLA)-4 expression, resistance could be overcome by combination with an anti-CTLA-4 monoclonal antibody (mAb). Patients who responded to combination therapy with anti-PD-1 and anti-CTLA-4 mAbs sequentially after primary resistance to PD-1 blockade monotherapy showed high Treg cell infiltration. We propose that the high antigenicity of Treg cells confers resistance to PD-1 blockade therapy via high PD-1 expression in Treg cells, which can be overcome by combination therapy with an anti-CTLA-4 mAb. en-copyright= kn-copyright= en-aut-name=MatsuuraHiroaki en-aut-sei=Matsuura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaToshifumi en-aut-sei=Ninomiya en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MutoYoshinori en-aut-sei=Muto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine,Okayama University kn-affil= affil-num=5 en-affil=Department of Dermatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=7 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=8 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=9 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine,Okayama University kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine,Okayama University kn-affil= affil-num=12 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=13 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= en-keyword=antigenicity kn-keyword=antigenicity en-keyword=cancer immunotherapy kn-keyword=cancer immunotherapy en-keyword=CTLA-4 kn-keyword=CTLA-4 en-keyword=PD-1 kn-keyword=PD-1 en-keyword=regulatory T cell kn-keyword=regulatory T cell 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=20250430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High-Resolution HPLC for Separating Peptide-Oligonucleotide Conjugates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Peptide-oligonucleotide conjugates (POCs) are chimeric molecules that combine the specificity of oligonucleotides with the functionality of peptides, improving the delivery and therapeutic potential of nucleic acid-based drugs. However, the analysis of POCs, particularly those containing arginine-rich sequences, poses major challenges because of aggregation caused by electrostatic interactions. In this study, we developed an optimized high-performance liquid chromatography (HPLC) method for analyzing POCs. Using a conjugate of DNA and nona-arginine as a model compound, we systematically investigated the effects of various analytical parameters, including column type, column temperature, mobile-phase composition, and pH. A column packed with C18 resin with wide pores combined with butylammonium acetate as the ion-pairing reagent and an optimal column temperature of 80 degrees C provided superior peak resolution and sensitivity. The optimized conditions gave clear separation of POCs from unlinked oligonucleotides and enabled the detection of nucleic acid fragments lacking an alkyne moiety as a linkage part, which is critical for quality control. Our HPLC method is robust and reproducible and substantially reduces the complexity, time, and cost associated with the POC analysis. The method may improve the efficiency of quality control in the production of POCs, thereby supporting their development as promising therapeutic agents for clinical applications. en-copyright= kn-copyright= en-aut-name=NaganumaMiyako en-aut-sei=Naganuma en-aut-mei=Miyako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiGenichiro en-aut-sei=Tsuji en-aut-mei=Genichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AmiyaMisato en-aut-sei=Amiya en-aut-mei=Misato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiraiReira en-aut-sei=Hirai en-aut-mei=Reira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiguchiYuki en-aut-sei=Higuchi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HataNaoko en-aut-sei=Hata en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NozawaSaoko en-aut-sei=Nozawa en-aut-mei=Saoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeDaishi en-aut-sei=Watanabe en-aut-mei=Daishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakajimaTaeko en-aut-sei=Nakajima en-aut-mei=Taeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DemizuYosuke en-aut-sei=Demizu en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=3 en-affil=YMC CO., LTD. kn-affil= affil-num=4 en-affil=YMC CO., LTD. kn-affil= affil-num=5 en-affil=YMC CO., LTD. kn-affil= affil-num=6 en-affil=YMC CO., LTD. kn-affil= affil-num=7 en-affil=YMC CO., LTD. kn-affil= affil-num=8 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=9 en-affil=YMC CO., LTD. kn-affil= affil-num=10 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Division of Pharmaceutical Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=214 cd-vols= no-issue= article-no= start-page=32 end-page=41 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=The Medaka approach to evolutionary social neuroscience en-subtitle= kn-subtitle= en-abstract= kn-abstract=Previously, the integration of comparative biological and neuroscientific approaches has led to significant advancements in social neuroscience. This review highlights the potential and future directions of evolutionary social neuroscience research utilizing medaka fishes (the family Adrianichthyidae) including Japanese medaka (Oryzias latipes). We focus on medaka social cognitive capabilities and mate choice behavior, particularly emphasizing mate preference using visual cues. Medaka fishes are also advantageous due to their abundant genetic resources, extensive genomic information, and the relative ease of laboratory breeding and genetic manipulation. Here we present some research examples of both the conventional neuroscience approach and evolutionary approach involving medaka fishes and other species. We also discuss the prospects of uncovering the molecular and cellular mechanisms underlying the diversity of visual mate preference among species. Especially, we introduce that the single-cell transcriptome technology, particularly in conjunction with 'Adaptive Circuitry Census', is an innovative tool that bridges comparative biological methods and neuroscientific approaches. Evolutionary social neuroscience research using medaka has the potential to unveil fundamental principles in neuroscience and elucidate the mechanisms responsible for generating diversity in mating strategies. en-copyright= kn-copyright= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Hiraki-KajiyamaTowako en-aut-sei=Hiraki-Kajiyama en-aut-mei=Towako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaRyutaro en-aut-sei=Ueda en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=YokoiSaori en-aut-sei=Yokoi en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatsumuraTakafumi en-aut-sei=Katsumura en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeuchiHideaki en-aut-sei=Takeuchi en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=3 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=4 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=5 en-affil=School of Pharmaceutical Sciences, Hokkaido University kn-affil= affil-num=6 en-affil=School of Medicine, Kitasato University kn-affil= affil-num=7 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= en-keyword=Evolutionary neuroscience kn-keyword=Evolutionary neuroscience en-keyword=Comparative neuroscience kn-keyword=Comparative neuroscience en-keyword=Medaka bioresource kn-keyword=Medaka bioresource en-keyword=Visual mate preference kn-keyword=Visual mate preference en-keyword=Sexual selection kn-keyword=Sexual selection en-keyword=Genetic manipulation kn-keyword=Genetic manipulation END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=2 article-no= start-page=e70091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250427 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Olanzapine enabled rechallenge after lorlatinib-induced psychosis: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Lorlatinib is a third-generation tyrosine kinase inhibitor for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). While it has a high intracranial lesion control rate, it can also cause central nervous system complications, including psychotic symptoms. We present a case of lorlatinib-induced psychosis successfully managed with olanzapine, enabling lorlatinib rechallenge.
Case Presentation: A 32-year-old woman with ALK-positive NSCLC and brain metastases was started on lorlatinib. After 18 months, she developed hallucinations and delusions. Despite treatment with risperidone, her psychotic symptoms persisted, leading to hospitalization. Her symptoms resolved upon lorlatinib discontinuation while risperidone was continued. Given the critical role of lorlatinib in controlling brain metastases, rechallenge was considered. To mitigate concerns regarding drug interactions, risperidone was replaced with olanzapine. Following lorlatinib rechallenge with olanzapine, no recurrence of psychiatric symptoms was observed, allowing continued lorlatinib treatment. Additionally, no progression of lung cancer was noted.
Conclusion: Lorlatinib is an essential drug for controlling brain metastases in ALK-positive NSCLC. However, it can induce psychotic symptoms. When psychiatrists are involved in managing adverse effects during cancer treatment, close collaboration among oncologists, psychiatrists, and patients is essential. en-copyright= kn-copyright= en-aut-name=YokodeAkiyoshi en-aut-sei=Yokode en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraYuko en-aut-sei=Nakamura en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=psycho-oncology kn-keyword=psycho-oncology en-keyword=lorlatinib kn-keyword=lorlatinib en-keyword=lung cancer kn-keyword=lung cancer en-keyword=medication-induced psychosis kn-keyword=medication-induced psychosis END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=1 article-no= start-page=4 end-page=6 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2023 Incentive Award of the Okayama Medical Association in General Medical Science (2023 Yuuki Prize) kn-title=令和５年度岡山医学会賞　総合研究奨励賞（結城賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SumiiYuichi en-aut-sei=Sumii en-aut-mei=Yuichi kn-aut-name=住居優一 kn-aut-sei=住居 kn-aut-mei=優一 aut-affil-num=1 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=岡山大学大学院医歯薬学総合研究科　血液・腫瘍・呼吸器内科学 END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=14323 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250424 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lymphatic flow dynamics under exercise load assessed with thoracic duct ultrasonography en-subtitle= kn-subtitle= en-abstract= kn-abstract=The thoracic duct (TD) is the largest lymphatic vessel proximal to the venous system. It undergoes morphological changes in response to lymph flow from the periphery, with automatic contraction controlling the dynamics to propel lymph toward the venous system. Recent advancements in ultrasonography have facilitated non-invasive observations of the TD’s terminal, including its valve and wall motions. Observations of TD movements allow predictions of lymphatic flow dynamics. However, no studies have yet documented the changes in the TD under exercise-induced lymph flow enhancement in humans. Here, using 18-MHz high-frequency ultrasonography, we demonstrate for the first time that the TD diameter significantly expands under exercise load. This study analyzed 20 participants; the maximum TD diameters at rest and post-exercise were 2.69?±?1.06 mm and 3.41?±?1.32 mm, respectively (p?=?0.00000056). While various methods exist for observing the TD, our approach?dynamically monitoring the TD diameter using sonography in real time and correlating it with lymphatic flow dynamics?offers a novel contribution. en-copyright= kn-copyright= en-aut-name=ShinaokaAkira en-aut-sei=Shinaoka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimataYoshihiro en-aut-sei=Kimata en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Lymphatics and Edematology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Plastic and Reconstructive surgery, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= en-keyword=Lymphedema kn-keyword=Lymphedema en-keyword=Lymphatic function kn-keyword=Lymphatic function en-keyword=Lymph flow kn-keyword=Lymph flow en-keyword=Chylothorax kn-keyword=Chylothorax en-keyword=Chylous ascites,lymph velocity kn-keyword=Chylous ascites,lymph velocity END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=2323 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A mini-hairpin shaped nascent peptide blocks translation termination by a distinct mechanism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Protein synthesis by ribosomes produces functional proteins but also serves diverse regulatory functions, which depend on the coding amino acid sequences. Certain nascent peptides interact with the ribosome exit tunnel to arrest translation and modulate themselves or the expression of downstream genes. However, a comprehensive understanding of the mechanisms of such ribosome stalling and its regulation remains elusive. In this study, we systematically screen for unidentified ribosome arrest peptides through phenotypic evaluation, proteomics, and mass spectrometry analyses, leading to the discovery of the arrest peptides PepNL and NanCL in E. coli. Our cryo-EM study on PepNL reveals a distinct arrest mechanism, in which the N-terminus of PepNL folds back towards the tunnel entrance to prevent the catalytic GGQ motif of the release factor from accessing the peptidyl transferase center, causing translation arrest at the UGA stop codon. Furthermore, unlike sensory arrest peptides that require an arrest inducer, PepNL uses tryptophan as an arrest inhibitor, where Trp-tRNATrp reads through the stop codon. Our findings illuminate the mechanism and regulatory framework of nascent peptide-induced translation arrest, paving the way for exploring regulatory nascent peptides. en-copyright= kn-copyright= en-aut-name=AndoYushin en-aut-sei=Ando en-aut-mei=Yushin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KoboAkinao en-aut-sei=Kobo en-aut-mei=Akinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NiwaTatsuya en-aut-sei=Niwa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamakawaAyako en-aut-sei=Yamakawa en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KonomaSuzuna en-aut-sei=Konoma en-aut-mei=Suzuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiYuki en-aut-sei=Kobayashi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NurekiOsamu en-aut-sei=Nureki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TaguchiHideki en-aut-sei=Taguchi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItohYuzuru en-aut-sei=Itoh en-aut-mei=Yuzuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ChadaniYuhei en-aut-sei=Chadani en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=2 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=3 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=4 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=6 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=7 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=8 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=9 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=10 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=116 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Colorectal cancer (CRC) is considered the third most common type of cancer worldwide. Tumor-associated macrophages (TAMs) have been shown to promote drug resistance. Adenosine-to-inosine RNA-editing, as regulated by adenosine deaminase acting on RNA (ADAR), is a process that induces the posttranscriptional modification of critical oncogenes. The aim of this study is to determine whether the signals from cancer cells would induce RNA-editing in macrophages.
Methods The effects of RNA-editing on phenotypes in macrophages were analyzed using clinical samples and in vitro and in vivo models.
Results The intensity of the RNA-editing enzyme ADAR1 (Adenosine deaminase acting on RNA 1) in cancer and mononuclear cells indicated a strong positive correlation between the nucleus and cytoplasm. The ADAR1-positive mononuclear cells were positive for CD68 and CD163, a marker for M2 macrophages. Cancer cells transport pro-inflammatory cytokines or ADAR1 protein directly to macrophages via the exosomes, promoting RNA-editing in AZIN1 (Antizyme Inhibitor 1) and GLI1 (Glioma-Associated Oncogene Homolog 1) and resulting in M2 macrophage polarization. GLI1 RNA-editing in the macrophages induced by cancer cells promotes the secretion of SPP1, which is supplied to the cancer cells. This activates the NF kappa B pathway in cancer cells, promoting oxaliplatin resistance. When the JAK inhibitors were administered, oncogenic RNA-editing in the macrophages was suppressed. This altered the macrophage polarization from M2 to M1 and decreased oxaliplatin resistance in cancer cells.
Conclusions This study revealed that ADAR1-high TAMs are crucial in regulating drug resistance in CRC and that targeting ADAR1 in TAMs could be a promising treatment approach for overcoming drug resistance in CRC. en-copyright= kn-copyright= en-aut-name=UmedaHibiki en-aut-sei=Umeda en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriwakeKazuya en-aut-sei=Moriwake en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakedaSho en-aut-sei=Takeda en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KishimotoHiroyuki en-aut-sei=Kishimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KayanoMasashi en-aut-sei=Kayano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MoriYoshiko en-aut-sei=Mori en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=GoelAjay en-aut-sei=Goel en-aut-mei=Ajay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=17 en-affil=Department of Obstetrics and Gynecology, Okayama University Gradu?ate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Comprehensive Cancer Center kn-affil= affil-num=24 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=RNA-editing kn-keyword=RNA-editing en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Chemoresistance kn-keyword=Chemoresistance en-keyword=Biomarker kn-keyword=Biomarker en-keyword=Colorectal cancer kn-keyword=Colorectal cancer END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=e70793 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic Differences and Distinct TP53 Mutation Site-Linked Chemosensitivity in Early- and Late-Onset Gastric Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Gastric cancer (GC) in younger patients often exhibits aggressive behavior and a poorer prognosis than that in older patients. Although the clinical differences may stem from oncogenic gene variations, it is unclear whether genetic differences exist between these groups. This study compared the genetic profiles of early- and late-onset GC and evaluated their impact on treatment outcomes.
Methods: We analyzed genetic data from 1284 patients with GC in the Japanese nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, comparing early-onset (<= 39 years; n = 143) and late-onset (>= 65 years; n = 1141) groups. The influence of TP53 mutations on the time to treatment failure (TTF) with platinum-based chemotherapy and the sensitivity of cancer cells with different TP53 mutation sites to oxaliplatin were assessed in vitro.
Results: Early- and late-onset GC showed distinct genetic profiles, with fewer neoantigen-associated genetic changes observed in early-onset cases. In particular, TP53 has distinct mutation sites; R175H and R273 mutations are more frequent in early- and late-onset GC, respectively. The R175H mutation showed higher sensitivity to oxaliplatin in vitro, consistent with the longer TTF in early-onset patients (17.3 vs. 7.0 months, p = 0.013) when focusing on the patients with TP53 mutations.
Conclusion: Genomic differences, particularly in TP53 mutation sites, between early- and late-onset GC support the need for age-specific treatment strategies. en-copyright= kn-copyright= en-aut-name=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=HirosunaKensuke en-aut-sei=Hirosuna en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OzatoToshiki en-aut-sei=Ozato en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=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, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=early-onset gastric cancer kn-keyword=early-onset gastric cancer en-keyword=oxaliplatin kn-keyword=oxaliplatin en-keyword=TP53 kn-keyword=TP53 END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=3 article-no= start-page=343 end-page=350 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characteristics of Early Gastric Cancer in a Patient with a History of Helicobacter pylori Infection and No History of Eradication Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective The characteristics of gastric cancer in patients with atrophic mucosa and no apparent history of Helicobacter pylori eradication have not been thoroughly investigated. Therefore, this study examined the clinicopathological characteristics of gastric cancer in these patients.
Methods We retrospectively examined the endoscopic and pathological characteristics of gastric cancer in patients who underwent endoscopic submucosal dissection.
Patients We divided the patients into 2 groups: those with gastric atrophy and no history of eradication (group A; n=102) and those with a history of eradication (group B; n=161). In group A, patients were further divided into mild atrophy (group C) and severe atrophy (group D) groups, while group B was further divided into those who underwent eradication treatment >5 years ago (group E) and those who underwent eradication 1-5 years ago (group F).
Results Group A comprised significantly older individuals (75±8.0 vs. 71±7.5 years old, p<0.001) with a higher frequency of elevated gastric cancer than group B (32.4% vs. 17.4%, p=0.006). Compared with group E, group A was older and had a greater incidence of elevated gastric cancer. The incidence of gastric cancer in the U or M region was lower in group C than in group D.
Conclusion Gastric cancer in patients with gastric atrophy and no history of eradication was associated with an older age and higher frequency of elevated-type morphology than in those with a history of eradication. en-copyright= kn-copyright= en-aut-name=KuraokaSakiko en-aut-sei=Kuraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=InoShoko en-aut-sei=Ino en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=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=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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 Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital 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 Hospital kn-affil= affil-num=9 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=autoimmune gastritis kn-keyword=autoimmune gastritis en-keyword=eradication kn-keyword=eradication en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=Helicobacter pylori kn-keyword=Helicobacter pylori END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250419 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Quantitative assessment of adhesive effects on partial and full compressive strength of LVL in the edge-wise direction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Laminated wood-based materials have been widely developed, and the laminating process and adhesive itself have been reported to enhance performance beyond the sum of the individual layers' performance. This phenomenon is particularly notable under loads applied in the "edge-wise direction", where each layer bears stress collectively. These combined effects are referred to as the "adhesive effect". Strength under partial compressive loads is critical in timber engineering, as partial compressive stress generates complex stress distributions influenced by boundary conditions. The adhesive effect may also be impacted by these conditions. The aim of this study was to quantitatively and directly evaluate the adhesive effect under partial and full compressive loads using various parameters. The strength of laminated veneer lumber (LVL) with adhesive was compared to that of simply layered veneers without adhesive to assess the adhesive effect. Three mechanisms contributing to the adhesive effect were proposed: Mechanism I, caused by the deformation of the adhesive layer independently from the veneers; Mechanism II, resulting from the adhesive impregnating the veneers; and Mechanism III, arising from the reinforcement provided by adjacent veneers. The results suggested the following: (i) Mechanism I had minimal impact, as the fiber direction and the presence of additional length showed strong and slight effects on the adhesive effect, respectively; (ii) Mechanism II contributed to preventing crack propagation and altering the relationships among mechanical properties, with its effectiveness increasing as the adhesive weight increased; and (iii) Mechanism III functioned as a crossband effect, reinforcing weaknesses caused by the slope of the grain and the angle of the annual rings. en-copyright= kn-copyright= en-aut-name=SudoRyutaro en-aut-sei=Sudo en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyamotoKohta en-aut-sei=Miyamoto en-aut-mei=Kohta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IdoHirofumi en-aut-sei=Ido en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Okayama University, Graduate School of Environmental, Life, Natural Science and Technology kn-affil= affil-num=2 en-affil=Forestry and Forest Products Research Institute kn-affil= affil-num=3 en-affil=Forestry and Forest Products Research Institute kn-affil= en-keyword=Laminated veneer lumber (LVL) kn-keyword=Laminated veneer lumber (LVL) en-keyword=Partial compressive load kn-keyword=Partial compressive load en-keyword=Bearing strength kn-keyword=Bearing strength en-keyword=Embedment strength kn-keyword=Embedment strength en-keyword=Partial compression perpendicular to grain (PCPG) kn-keyword=Partial compression perpendicular to grain (PCPG) en-keyword=Adhesive layer kn-keyword=Adhesive layer END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=4 article-no= start-page=e70151 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Frequency and Characteristics of Gastrointestinal Diseases in Patients With Neurofibromatosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Patients with neurofibromatosis (NF) frequently experience gastrointestinal symptoms, but the specific characteristics of these lesions are not well understood.
Methods: To investigate the prevalence and nature of gastrointestinal diseases in this population, we analyzed the gastrointestinal lesions identified through endoscopic examinations in patients with NF.
Results: We included 225 patients with NF type 1 (NF1) and 15 with NF type 2 (NF2). None of the NF2 patients underwent endoscopy. Among the NF1 patients, 27 received endoscopies, and 13 (59%) had gastrointestinal lesions. These 13 patients were predominantly male (10 males and three females), with a median age of 53 years (range: 19-76 years). The identified lesions included colorectal polyps (n = 6), gastrointestinal stromal tumors ([GIST], n = 4), subepithelial lesions (n = 3), gastric fundic gland polyps (n = 3), diffuse intestinal ganglioneuromatosis (n = 2), esophageal polyps (n = 2), a Schwann cell hamartoma (n = 1), esophageal cancer (n = 1), and a gastric hyperplastic polyp (n = 1). All GISTs and one case of diffuse intestinal ganglioneuromatosis were surgically resected. Interestingly, six out of 13 patients were asymptomatic. Additionally, all patients who required surgery were 40 years of age or older.
Conclusions: These findings suggest that routine endoscopic examinations, along with imaging techniques like computed tomography and magnetic resonance imaging, could be beneficial for the early detection of gastrointestinal lesions in NF1 patients aged 40 and above. en-copyright= kn-copyright= en-aut-name=HondaManami en-aut-sei=Honda en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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 Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, 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 Practical Gastrointestinal Endoscopy,Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=colonoscopy kn-keyword=colonoscopy en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=gastrointestinal neoplasms kn-keyword=gastrointestinal neoplasms en-keyword=gastrointestinal stromal tumor kn-keyword=gastrointestinal stromal tumor en-keyword=neurofibromatosis kn-keyword=neurofibromatosis END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=139 end-page=144 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Safe Resection of Esophageal Cancer with a Non-Recurrent Inferior Laryngeal Nerve Associated with an Aberrant Right Subclavian Artery Using Intraoperative Nerve Monitoring en-subtitle= kn-subtitle= en-abstract= kn-abstract=In thoracic esophageal cancer, lymph node dissection around the recurrent laryngeal nerve is crucial but poses a risk of nerve palsy, affecting postoperative quality of life. In cases with an aberrant right subclavian artery (ARSA), the right recurrent laryngeal nerve is absent, and the non-recurrent inferior laryngeal nerve (NRILN) enters the larynx directly from the vagus nerve in the cervical region. Identifying the course of the NRILN is vital to avoid injury. A case of esophageal cancer with an ARSA, in which the course of the NRILN was preserved using the Nerve Integrity Monitoring (NIM) system during surgery, is described. en-copyright= kn-copyright= en-aut-name=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige 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=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizusawaYohei en-aut-sei=Mizusawa en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KondoYuhei en-aut-sei=Kondo en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanoueYukinori en-aut-sei=Tanoue en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=intraoperative nerve monitoring kn-keyword=intraoperative nerve monitoring en-keyword=aberrant right subclavian artery kn-keyword=aberrant right subclavian artery en-keyword=non-recurrent inferior laryngeal nerve kn-keyword=non-recurrent inferior laryngeal nerve en-keyword=thoracoscopic esophagectomy kn-keyword=thoracoscopic esophagectomy END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=129 end-page=134 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Retinitis Pigmentosa Diagnosed with Severe Anterior Capsule Contraction after Cataract Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 66-year-old woman presented with significant anterior capsule contraction and intraocular lens dislocation in both eyes 4 months after cataract surgery. Postoperative examinations such as fluorescein angiography, Goldmann perimetry, and electroretinography revealed retinitis pigmentosa (RP). Patients with significant anterior capsule contraction after cataract surgery should be closely examined because RP may be a contributing factor. en-copyright= kn-copyright= en-aut-name=TsujiAkihiro en-aut-sei=Tsuji en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosokawaMio en-aut-sei=Hosokawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiKosuke en-aut-sei=Takahashi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=Fukuyama City Hospital, Fukuyama City kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=retinitis pigmentosa kn-keyword=retinitis pigmentosa en-keyword=intraocular lens kn-keyword=intraocular lens en-keyword=anterior capsule contraction kn-keyword=anterior capsule contraction END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=123 end-page=127 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Macular Hole Formation Six Months after Hemorrhage Displacement for Submacular and Henle Fiber Layer Hemorrhage due to Retinal Arterial Macroaneurysm Rupture en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 78-year-old woman presented with sudden vision loss and central scotoma. Visual acuity in the right eye was 20/222, with submacular hemorrhage (SMH) and Henle fiber layer hemorrhage (HFLh) due to retinal arterial macroaneurysm (RAM) rupture. She underwent SMH displacement, including cataract surgery, vitrectomy, intravitreal injection of tissue-plasminogen activator, and air tamponade. Three months postoperatively the SMH and HFLh had disappeared and visual acuity had improved to 20/200. Six months postoperatively, a macular hole had developed. We performed an inverted internal limiting membrane flap and gas tamponade. Ten months later, the hole had closed and visual acuity had improved to 20/100. en-copyright= kn-copyright= en-aut-name=AkatsukaRiku en-aut-sei=Akatsuka en-aut-mei=Riku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Morizane HosokawaMio en-aut-sei=Morizane Hosokawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoiShinichiro en-aut-sei=Doi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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= affil-num=8 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=submacular hemorrhage kn-keyword=submacular hemorrhage en-keyword=Henle fiber layer hemorrhage kn-keyword=Henle fiber layer hemorrhage en-keyword=retinal arterial macroaneurysm rupture kn-keyword=retinal arterial macroaneurysm rupture en-keyword=macular hole kn-keyword=macular hole en-keyword=inverted internal limiting membrane flap technique kn-keyword=inverted internal limiting membrane flap technique END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=117 end-page=121 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=From a Congenital Defect to Cancer: A Case of Squamous Cell Carcinoma in a Neglected Myelomeningocele en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neural tube defects are common congenital anomalies, typically presenting early due to visible swelling and/or neurological deficits. Rarely, cystic swellings are neglected until adulthood, with only 14 cases of malignancy developing in an untreated meningomyelocele reported to date. We describe the case details of a 26-year-old Indian woman with this rare complication. Magnetic resonance imaging revealed a low-lying spinal cord with spinal dysraphism, cord herniation, and a cystic lesion. The biopsy confirmed a well-differentiated squamous cell carcinoma. Malignant transformation in an untreated myelomeningocele is rare, with chronic irritation and infection as proposed causes. Early biopsy and treatment are crucial for its management. en-copyright= kn-copyright= en-aut-name=GautamAbhishek en-aut-sei=Gautam en-aut-mei=Abhishek kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KenawadekarRahul en-aut-sei=Kenawadekar en-aut-mei=Rahul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HattiholiVirupaxi en-aut-sei=Hattiholi en-aut-mei=Virupaxi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MastePraful Suresh en-aut-sei=Maste en-aut-mei=Praful Suresh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Neurosurgery, Jawaharlal Nehru Medical College, KAHER kn-affil= affil-num=2 en-affil=Department of General Surgery, Jawaharlal Nehru Medical College, KAHER kn-affil= affil-num=3 en-affil=Department of Radiology, Jawaharlal Nehru Medical College, KAHER kn-affil= affil-num=4 en-affil=Department of Neurosurgery, Jawaharlal Nehru Medical College, KAHER kn-affil= en-keyword=squamous cell carcinoma kn-keyword=squamous cell carcinoma en-keyword=meningomyelocele kn-keyword=meningomyelocele en-keyword=occult spinal dysraphism kn-keyword=occult spinal dysraphism END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=81 end-page=92 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Outcomes of Neoadjuvant Paclitaxel/Cisplatin/Gemcitabine Compared with Gemcitabine/Cisplatin for Muscle-Invasive Bladder Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=We retrospectively evaluated the oncologic outcomes of paclitaxel, cisplatin, and gemcitabine (PCG) with those of gemcitabine and cisplatin (GC) as neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients. The primary outcome was efficacy: pathological complete response (pCR), ypT0N0; and pathological objective response (pOR), ypT0N0, ? ypT1N0, or ypT0N1. Secondary outcomes included overall survival (OS), recurrence-free survival (RFS), predictive factors for pOR, OS, and RFS, and hematologic adverse events (AEs). Among 113 patients treated (PCG, n=28; GC, n=85), similar pOR and pCR rates were achieved by the groups (pOR: PCG, 57.1% vs. GC, 49. 4%; p=0.52; pCR: PCG, 39.3% vs. GC, 29.4%; p=0.36). No significant differences were observed in OS (p=1.0) or RFS (p=0.20). Multivariate logistic regression analysis showed that hydronephrosis (odds ratio [OR] 0.32, 95%CI: 0.11-0.92) and clinical node-positive status (cN+) (OR 0.22, 95%CI: 0.050-0.99) were significantly associated with a decreased probability of pOR. On multivariate Cox regression analyses, pOR achievement was associated with improved OS (hazard ratio [HR] 0.23, 95%CI: 0.10-0.56) and RFS (HR 0.30, 95%CI: 0.13-0.67). There were no significant between-group differences in the incidence of grade ? 3 hematologic AEs or dose-reduction required, but the PCG group had a higher incidence of grade 4 neutropenia. en-copyright= kn-copyright= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TsugawaTakuji en-aut-sei=Tsugawa en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboiKazuma en-aut-sei=Tsuboi en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 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=9 ORCID= en-aut-name=EbaraShin en-aut-sei=Ebara en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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, Hiroshima City Hiroshima Citizens Hospital 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, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=urothelial carcinoma kn-keyword=urothelial carcinoma en-keyword=paclitaxel kn-keyword=paclitaxel en-keyword=cisplatin kn-keyword=cisplatin en-keyword=gemcitabine kn-keyword=gemcitabine en-keyword=neoadjuvant kn-keyword=neoadjuvant END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=65 end-page=73 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between the Pretreatment Body Mass Index and Anamorelin’s Efficacy in Patients with Cancer Cachexia: A Retrospective Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anamorelin (ANAM) is used to treat cancer-associated cachexia, a syndrome involving muscle loss and anorexia. The timing of the initiation of ANAM treatment is crucial to its efficacy. Although the body mass index (BMI) is a diagnostic criterion for cancer cachexia, no studies have explored its association with ANAM efficacy. We conducted a single-center, retrospective cohort study to investigate the association between the pre-treatment BMI and ANAM efficacy in patients with cancer-associated cachexia (n=47). The ANAM treatment was considered effective if the patient’s appetite improved within 30 days of treatment initiation. We calculated a BMI cutoff value (19.5 kg/m2) and used it to divide the patients into high- and low-BMI groups. Their background, clinical laboratory values, cancer types, and treatment lines were investigated. Twenty (42.6%) had a high BMI (? 19.5 kg/m2) and 27 (57.4%) had a low BMI (< 19.5 kg/m2). High BMI was significantly associated with ANAM effectiveness (odds ratio 7.86, 95% confidence interval 1.99-31.00, p=0.003). Together these results indicate that it is beneficial to initiate ANAM treatment before a patient’s BMI drops below 19.5 kg/m2. Our findings will help advance cancer cachexia treatment and serve as a reference for clinicians to predict ANAM’s efficacy. en-copyright= kn-copyright= en-aut-name=MakiMasatoshi en-aut-sei=Maki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakadaRyo en-aut-sei=Takada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshigoTomoyuki en-aut-sei=Ishigo en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraMiki en-aut-sei=Fujiwara en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiYoko en-aut-sei=Takahashi en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaShinya en-aut-sei=Otsuka en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TamuraKoji en-aut-sei=Tamura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamaokaTerutaka en-aut-sei=Hamaoka en-aut-mei=Terutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Pharmacy, Sapporo Medical University Hospital kn-affil= affil-num=4 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=8 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= en-keyword=anamorelin kn-keyword=anamorelin en-keyword=cancer-associated cachexia kn-keyword=cancer-associated cachexia en-keyword=body mass index kn-keyword=body mass index en-keyword=albumin kn-keyword=albumin en-keyword=efficacy rate kn-keyword=efficacy rate END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=2 article-no= start-page=131 end-page=136 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=Effect of calcium supplementation on bone deformity and histopathological findings of skin papules in a pediatric patient with vitamin D?dependent rickets type 2A: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vitamin D?dependent rickets type 2A (VDDR2A) is an autosomal recessive disease caused by pathogenic variants of the vitamin D receptor (VDR) gene. VDDR2A rickets are usually resistant to native or active vitamin D treatment because of impaired active calcium absorption against the calcium concentration gradient, which is a ligand-dependent VDR action in the small intestine. Alopecia due to an impaired skin follicular cycle is occasionally observed in patients with VDDR2A. Among the pathogenic VDR variants, most in the DNA-binding domain and some in the ligand-binding domain, which affect the dimerization of VDR with the retinoic X receptor, are associated with alopecia. Herein, we report a case of VDDR2A caused by compound heterozygous pathogenic variants of the DNA-binding domain of VDR. Active vitamin D treatment did not ameliorate genu varum, rachitic changes in the roentgenogram, or abnormal laboratory findings. However, oral administration of calcium lactate dramatically improved these findings. The patient also experienced hair loss at two months of age and multiple papules on the skin at two yr of age, which did not improve with vitamin D or calcium supplementation. We also report the histopathological findings of skin papules in this patient. en-copyright= kn-copyright= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyakeTomoko en-aut-sei=Miyake en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobashiMina en-aut-sei=Kobashi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AgoYuko en-aut-sei=Ago en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FutagawaNatsuko en-aut-sei=Futagawa en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyaharaHiroyuki en-aut-sei=Miyahara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiguchiYousuke en-aut-sei=Higuchi en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=rickets kn-keyword=rickets en-keyword=receptor kn-keyword=receptor en-keyword=alopecia kn-keyword=alopecia en-keyword=papules kn-keyword=papules en-keyword=calcium kn-keyword=calcium 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=20250410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enterobacterial common antigen repeat-unit flippase WzxE is required for Escherichia coli growth under acidic conditions, low temperature, and high osmotic stress conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colanic acid and enterobacterial common antigen (ECA) are cell-surface polysaccharides that are produced by many Escherichia coli isolates. Colanic acid is induced under acidic, low temperature, and high-salt conditions and is important for E. coli resistance to these stresses; however, the role of ECA in these stresses is less clear. Here, we observed that knockout of flippase wzxE, which translocates lipid-linked ECA repeat units from the cytoplasmic side of the inner membrane to the periplasmic side, resulted in the sensitivity of E. coli BW25113 to acidic conditions. The wzxE-knockout mutant showed reduced growth potential and viable counts in vegetable extracts with acidic environments, including cherry tomatoes, carrots, celery, lettuce, and spinach. A double-knockout strain of wzxE and wecF (glycosyltransferase that adds the third-and-final sugar of the lipid-linked ECA repeat unit) was not sensitive to acidic conditions, with similar results obtained for a double-knockout strain of wzxE and wcaJ (glycosyltransferase that initiates colanic acid lipid-linked repeat-unit biosynthesis). The wzxE-knockout mutant was sensitive to low temperatures or high-salt conditions, which induced colanic acid synthesis, and these sensitivities were abolished by the additional knockout of wcaJ. These results suggest that lipid-linked ECA repeat units confer E. coli susceptibility to acidic, low temperatures, and high-salt conditions in a colanic acid-dependent manner and that wzxE suppresses this negative effect. en-copyright= kn-copyright= en-aut-name=YamaguchiSaki en-aut-sei=Yamaguchi en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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= en-keyword=wzxE flippase kn-keyword=wzxE flippase en-keyword=enterobacterial common antigen kn-keyword=enterobacterial common antigen en-keyword=low pH kn-keyword=low pH en-keyword=low temperature kn-keyword=low temperature en-keyword=hyperosmotic stress kn-keyword=hyperosmotic stress END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=7 article-no= start-page=2221 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Length Estimation of Pneumatic Artificial Muscle with Optical Fiber Sensor Using Machine Learning en-subtitle= kn-subtitle= en-abstract= kn-abstract=A McKibben artificial muscle is a soft actuator driven by air pressure, characterized by its flexibility, lightweight design, and high power-to-weight ratio. We have developed a smart artificial muscle that is capable of sensing its motion. To enable this sensing function, an optical fiber was integrated into the sleeve consisting of multiple fibers and serving as a component of the McKibben artificial muscle. By measuring the macrobending loss of the optical fiber, the length of the smart artificial muscle is expected to be estimated. However, experimental results indicated that the sensor's characteristics depend not only on the length but also on the load and the applied air pressure. This dependency arises because the stress applied to the optical fiber increases, causing microbending loss. In this study, we employed a machine learning model, primarily composed of Long Short-Term Memory (LSTM) neural networks, to estimate the length of the smart artificial muscle. The experimental results demonstrate that the length estimation obtained through machine learning exhibits a smaller error. This suggests that machine learning is a feasible approach to enhancing the length measurement accuracy of the smart artificial muscle. en-copyright= kn-copyright= en-aut-name=NiYilei en-aut-sei=Ni en-aut-mei=Yilei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WakimotoShuichi en-aut-sei=Wakimoto en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TianWeihang en-aut-sei=Tian en-aut-mei=Weihang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TodaYuichiro en-aut-sei=Toda en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KandaTakefumi en-aut-sei=Kanda en-aut-mei=Takefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamaguchiDaisuke en-aut-sei=Yamaguchi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=McKibben artificial muscle kn-keyword=McKibben artificial muscle en-keyword=machine learning kn-keyword=machine learning en-keyword=optical fiber kn-keyword=optical fiber en-keyword=motion estimation kn-keyword=motion estimation END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=2 article-no= start-page=100016 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Changes in adrenoceptor expression level contribute to the cellular plasticity of glioblastoma cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glioblastoma cells are known to regulate their cellular plasticity in response to their surrounding microenvironment, but it is not fully understood what factors contribute to the cells' changing plasticity. Here, we found that glioblastoma cells alter the expression level of adrenoreceptors depending on their differentiation stage. Catecholamines are abundant in the central nervous system, and we found that noradrenaline, in particular, enhances the stemness of glioblastoma cells and promotes the dedifferentiation potential of already differentiated glioblastoma cells. Antagonist and RNAi experiments revealed that signaling through alpha 1D-adrenoreceptor is important for noradrenaline action on glioblastoma cells. We also found that high alpha 1Dadrenoreceptor expression was associated with poor prognosis in patients with gliomas. These data suggest that glioblastoma cells increase the expression level of their own adrenoreceptors to alter the surrounding tumor microenvironment favorably for survival. We believe that our findings will contribute to the development of new therapeutic strategies for glioblastoma. en-copyright= kn-copyright= en-aut-name=AsakaYutaro en-aut-sei=Asaka en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasumotoToshio en-aut-sei=Masumoto en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UnedaAtsuhito en-aut-sei=Uneda en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=PenaTirso en-aut-sei=Pena en-aut-mei=Tirso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AndoTeruhiko en-aut-sei=Ando en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HuangRongsheng en-aut-sei=Huang en-aut-mei=Rongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Health Administration and Promotion, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=6 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Trauma Orthopedics, The Second Hospital of Dalian Medical University kn-affil= affil-num=11 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Adrenoceptors kn-keyword=Adrenoceptors en-keyword=Glioma stem-like cells kn-keyword=Glioma stem-like cells en-keyword=Differentiated glioma cells kn-keyword=Differentiated glioma cells en-keyword=Noradrenaline kn-keyword=Noradrenaline en-keyword=Cellular plasticity kn-keyword=Cellular plasticity 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=20250403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The association between objectively measured physical activity and home blood pressure: a population-based real-world data analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Few studies have examined the association of objectively measured habitual physical activity (PA) and sedentary behavior with out-of-office blood pressure (BP). We investigated the associations of objectively measured PA intensity time, sedentary time, and step count with at-home BP. Using accelerometer-recorded PA indices and self-measured BP in 368 participants (mean age, 53.8 years; 58.7% women), we analyzed 115,575 records of each parameter between May 2019 and April 2024. PA intensities were categorized as light (2.0?2.9 metabolic equivalents [METs]); moderate (3.0?5.9 METs); vigorous (?6.0 METs), or sedentary (<2.0 METs): the median [interquartile ranges] for these variables was 188 [146?232], 83 [59?114], 1 [0?2], 501 [428?579] minutes, respectively, and for step count, was 6040 [4164?8457]. Means [standard deviations] for systolic and diastolic BP were 116.4 [14.2] and 75.2 [9.3] mmHg, respectively. A mixed-effect model adjusted for possible confounders showed that 1-h longer in vigorous PA was associated with lower systolic and diastolic BP (?1.69 and ?1.09?mmHg, respectively). A 1000-step increase in step count was associated with lower systolic and diastolic BP (?0.05 and ?0.02?mmHg, respectively). Associations were more pronounced among men and participants aged <60 years. Sedentary time was positively associated with BP in men and participants aged <60 years, but inversely associated with BP in women and participants aged ?60 years. Our findings suggest that more PA and less sedentary behavior were associated with BP reduction, particularly among men and participants aged <60 years. However, the clinical relevance of this effect remains uncertain because of its modest magnitude. en-copyright= kn-copyright= en-aut-name=KinutaMinako en-aut-sei=Kinuta en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=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=NakahataNoriko en-aut-sei=Nakahata en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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 Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine 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 Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition kn-affil= affil-num=6 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=213 cd-vols= no-issue= article-no= start-page=128 end-page=137 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The potential mechanism maintaining transactive response DNA binding protein 43?kDa in the mouse stroke model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The disruption of transactive response DNA binding protein 43?kDa (TDP-43) shuttling leads to the depletion of nuclear localization and the cytoplasmic accumulation of TDP-43. We aimed to evaluate the mechanism underlying the behavior of TDP-43 in ischemic stroke. Adult male C57BL/6?J mice were subjected to 30 or 60?min of transient middle cerebral artery occlusion (tMCAO), and examined at 1, 6, and 24?h post reperfusion. Immunostaining was used to evaluate the expression of TDP-43, G3BP1, HDAC6, and RAD23B. The total and cytoplasmic number of TDP-43?positive cells increased compared with sham operation group and peaked at 6?h post reperfusion after tMCAO. The elevated expression of G3BP1 protein peaked at 6?h after reperfusion and decreased at 24?h after reperfusion in ischemic mice brains. We also observed an increase of expression level of HDAC6 and the number of RAD23B-positive cells increased after tMCAO. RAD23B was colocalized with TDP-43 24?h after tMCAO. We proposed that the formation of stress granules might be involved in the mislocalization of TDP-43, based on an evaluation of G3BP1 and HDAC6. Subsequently, RAD23B, may also contribute to the downstream degradation of mislocalized TDP-43 in mice tMCAO model. en-copyright= kn-copyright= en-aut-name=BianYuting en-aut-sei=Bian en-aut-mei=Yuting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Ota-ElliottRicardo Satoshi en-aut-sei=Ota-Elliott en-aut-mei=Ricardo Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HuXinran en-aut-sei=Hu en-aut-mei=Xinran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SunHongming en-aut-sei=Sun en-aut-mei=Hongming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BianZhihong en-aut-sei=Bian en-aut-mei=Zhihong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhaiYun en-aut-sei=Zhai en-aut-mei=Yun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YuHaibo en-aut-sei=Yu en-aut-mei=Haibo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HuXiao en-aut-sei=Hu en-aut-mei=Xiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AnHangping en-aut-sei=An en-aut-mei=Hangping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=LiuHongzhi en-aut-sei=Liu en-aut-mei=Hongzhi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=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= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=TDP-43 kn-keyword=TDP-43 en-keyword=ALS kn-keyword=ALS en-keyword=RNA-binding protein kn-keyword=RNA-binding protein en-keyword=Mislocalization kn-keyword=Mislocalization en-keyword=G3BP1 kn-keyword=G3BP1 en-keyword=HDAC6 kn-keyword=HDAC6 en-keyword=RAD23B kn-keyword=RAD23B en-keyword=tMCAO kn-keyword=tMCAO END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=4 article-no= start-page=e82348 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bilateral Scleritis and Neutrophilic Dermatosis With Cytogenetic Chromosomal Aberrancy Related to Pyoderma Gangrenosum: A Case Report of a 20-Year Follow-Up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pyoderma gangrenosum is a non-infectious autoimmune disease with skin plaques and ulcers in the entity of neutrophilic dermatosis and may have a background of myelodysplastic syndromes. This study reported a 20-year follow-up of a patient with pyoderma gangrenosum and scleritis who showed chromosomal aberrancy from the initial phase and later in the course developed thrombocythemia. A 51-year-old man presented with widespread indurated erythematous plaques with scaling and pustules on the forehead, bilateral eyelids, and nasal bridge, in addition to nodular scleritis in the left eye and ulcer formation of the plaques in the lower legs. Skin biopsy revealed massive dermal infiltration mainly with neutrophils in the absence of neutrophilic vasculitis. Suspected of myelodysplastic syndromes, bone marrow biopsy was normal, while chromosomal aberrancy, 46, XY, del (20) (q11q13.3), was detected. In the diagnosis of neutrophilic dermatosis, probably of pyoderma gangrenosum, he began to have oral prednisolone 20 mg daily and colchicine 1 mg daily, leading to the subsidence of skin lesions. Four months later, he developed nodular scleritis in the right eye and began to use topical 0.1% betamethasone in both eyes. He was stable with only prednisolone 12.5 mg daily until the age of 55.5 years, when he showed an increase of serum lactate dehydrogenase. The bone marrow aspirate disclosed neither blast cell increase nor atypical cells. The same chromosomal aberrancy was repeatedly detected. One year later, he developed breathing difficulty and underwent tracheostomy. Laryngeal lesion biopsy disclosed squamous cell papilloma with human papillomavirus-6. At 60 years old, he showed marginal corneal infiltration in the left eye, and at 61 years old, hypopyon in the right eye. Platelets tended to increase up to 1000 × 103/?L, and bone marrow examinations were recommended but refused by the patient. At the latest follow-up at 71 years old, he was ambulatory in health and stable with a tracheostomy cannula. In conclusion, pyoderma gangrenosum with scleritis occurred in an undetermined hematological malignancy with chromosomal aberrancy. 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=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ObikaMikako en-aut-sei=Obika en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of General Internal Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=corneal infiltration kn-keyword=corneal infiltration en-keyword=hypopyon kn-keyword=hypopyon en-keyword=myelodysplastic syndromes kn-keyword=myelodysplastic syndromes en-keyword=neutrophilic dermatosis kn-keyword=neutrophilic dermatosis en-keyword=peripheral keratitis kn-keyword=peripheral keratitis en-keyword=pyoderma gangrenosum kn-keyword=pyoderma gangrenosum en-keyword=scleritis kn-keyword=scleritis en-keyword=sweet syndrome kn-keyword=sweet syndrome END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=1 article-no= start-page=141 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary chest wall sarcoma: advances in surgical management and outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Although rare, primary chest wall sarcomas are complex malignancies necessitating optimal local control and comprehensive treatment. This study aimed to review 9 years of cases of primary chest wall sarcomas at a single institution, focusing on their histology, surgical management, and prognosis.
Methods A retrospective analysis was performed on 19 patients undergoing chest wall resection for sarcoma from 2012 to 2020. Data on demographics, tumor specifics, resection extent, and adjuvant therapies were collected. Surgical and postoperative outcomes were also assessed.
Results The median patient age was 64 years. Chondrosarcoma was the most common histology. R0 resection was achieved in all patients, with early postoperative complications occurring in 11% of the patients. Robust chest wall reconstruction was performed, resulting in minimal respiratory complications. The 5-year overall survival and disease-free survival rates were 94% and 68%, respectively. Tumor size and patient age were significant prognostic factors for local recurrence.
Conclusion Comprehensive surgical resection, coupled with multidisciplinary preoperative planning, achieves favorable outcomes. Patients aged???70 years and with tumor size???5 cm (P?=?.047) should be carefully followed up for local recurrence. en-copyright= kn-copyright= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin 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=RyukoTsuyoshi en-aut-sei=Ryuko en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomiokaYasuaki en-aut-sei=Tomioka en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= affil-num=1 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=2 en-affil= kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=5 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=6 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=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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 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=10 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=11 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=12 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=Primary chest wall sarcomas kn-keyword=Primary chest wall sarcomas en-keyword=Chest wall resection kn-keyword=Chest wall resection en-keyword=Chondrosarcoma kn-keyword=Chondrosarcoma en-keyword=Robust chest wall reconstruction kn-keyword=Robust chest wall reconstruction END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=3 article-no= start-page=e0320482 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Serum uric acid level is associated with renal arteriolar hyalinosis and predicts post-donation renal function in living kidney donors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Major guidelines for living-donor kidney transplantation underscore the need for pre-donation evaluation of renal function, hypertension, obesity, diabetes mellitus, and albuminuria to minimize the risk of donation from marginal donors. However, validity is yet to be established. We retrospectively investigated the relationship between clinical characteristics and histological indices in baseline renal biopsies (0-h biopsies) and whether these parameters could predict renal function in living kidney donors one year post-donation. Seventy-six living kidney donors were recruited for this study. In histological analyses, glomerulosclerosis, arteriosclerosis, arteriolosclerosis, arteriolar hyalinosis, and interstitial fibrosis and tubular atrophy scores/indices were evaluated. Post-donation serum creatinine levels in kidney donors with arteriolar hyalinosis were significantly higher than those in individuals without arteriolar hyalinosis. There was a significant correlation between baseline serum uric acid levels and the arteriolar hyalinosis index, with baseline uric acid level identified as an independent factor for hyalinosis in multiple regression analysis. Additionally, the serum uric acid level was a significant prognostic factor for post-donation serum creatinine after adjustment for baseline clinical parameters. These data demonstrate that pre-donation serum uric acid levels are associated with arteriolar hyalinosis in the kidney and could predict a decline in renal function during the first year after donation in living kidney donors. en-copyright= kn-copyright= en-aut-name=KanoYuzuki en-aut-sei=Kano en-aut-mei=Yuzuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitagawaMasashi en-aut-sei=Kitagawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=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=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke 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=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo 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=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medicine, Kawasaki Medical School General Medical Center and Department of Medical Care Work, Kawasaki College of Health Professions 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 Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=4 article-no= start-page=e70139 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= 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=Background and Aim: Oral tacrolimus is an effective treatment for refractory ulcerative colitis (UC). However, tacrolimus is underutilized because of the difficulties in transitioning to subsequent maintenance therapy and concerns about adverse events.
Methods: We evaluated the clinical outcomes, adverse events, and accumulated medication costs in consecutive 72 UC patients treated with tacrolimus.
Results: Fifty-five (76%) patients with pancolitis and 43 (60%) patients with acute severe disease were entered. Fifty-four (75%) achieved clinical remission 8 weeks after starting tacrolimus. At the last visit, 62 (86%) patients had colectomy-free remission, and 55 (76%) patients had corticosteroid-free remission. Eighteen (25%) patients maintained remission without additional treatment after tacrolimus discontinuation. Patients with continuous remission had a significantly lower history of thiopurine use and lower serum albumin levels at the induction of tacrolimus than patients with failure to induce or maintain remission. No severe adverse events due to tacrolimus treatment were observed. The accumulated medication costs over 3 years in patients with continuous remission after the start of tacrolimus were lower than those in patients with induction and maintenance of infliximab (p < 0.001).
Conclusions: Tacrolimus could have an irreplaceable role in the era of biologic therapies, especially for refractory UC patients with thiopurine-na & iuml;ve and low serum albumin levels. en-copyright= kn-copyright= en-aut-name=IgawaShoko en-aut-sei=Igawa en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ToyosawaJunki en-aut-sei=Toyosawa en-aut-mei=Junki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AoyamaYuki en-aut-sei=Aoyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KinugasaHideaki en-aut-sei=Kinugasa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki 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 Gastroenterology and Hepatology, 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 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 Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=biologics therapy kn-keyword=biologics therapy en-keyword=tacrolimus kn-keyword=tacrolimus en-keyword=thiopurine kn-keyword=thiopurine en-keyword=ulcerative colitis kn-keyword=ulcerative colitis END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=1 article-no= start-page=29 end-page=51 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=The Quillen model structure on the category of diffeological spaces en-subtitle= kn-subtitle= en-abstract= kn-abstract=We construct on the category of diffeological spaces a Quillen model structure having smooth weak homotopy equivalences as the class of weak equivalences. en-copyright= kn-copyright= en-aut-name=HaraguchiTadayuki en-aut-sei=Haraguchi en-aut-mei=Tadayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimakawaKazuhisa en-aut-sei=Shimakawa en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Education for Human Growth, Nara Gakuen University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= en-keyword=Diffeological space kn-keyword=Diffeological space en-keyword=Homotopy theory kn-keyword=Homotopy theory en-keyword=Model category kn-keyword=Model category END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=1 article-no= start-page=100 end-page=107 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=Investigating the Effects of Reconstruction Conditions on Image Quality and Radiomic Analysis in Photon-counting Computed Tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction:Photon-counting computed tomography (CT) is equipped with an adaptive iterative reconstruction method called quantum iterative reconstruction (QIR), which allows the intensity to be changed during image reconstruction. It is known that the reconstruction conditions of CT images affect the analysis results when performing radiomic analysis. The aim of this study is to investigate the effect of QIR intensity on image quality and radiomic analysis of renal cell carcinoma (RCC).
Materials and Methods:The QIR intensities were selected as off, 2 and 4. The image quality evaluation items considered were task-based transfer function (TTF), noise power spectrum (NPS), and low-contrast object specific contrast-to-noise ratio (CNRLO). The influence on radiomic analysis was assessed using the discrimination accuracy of clear cell RCC.
Results:For image quality evaluation, TTF and NPS values were lower and CNRLO values were higher with increasing QIR intensity; for radiomic analysis, sensitivity, specificity, and accuracy were higher with increasing QIR intensity. Principal component analysis and receiver operating characteristics analysis also showed higher values with increasing QIR intensity.
Conclusion:It was confirmed that the intensity of the QIR intensity affects both the image quality and the radiomic analysis. en-copyright= kn-copyright= en-aut-name=OhataMiyu en-aut-sei=Ohata en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuiRyohei en-aut-sei=Fukui en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimitsuYusuke en-aut-sei=Morimitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiDaichi en-aut-sei=Kobayashi en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamauchiTakatsugu en-aut-sei=Yamauchi en-aut-mei=Takatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkagiNoriaki en-aut-sei=Akagi en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HondaMitsugi en-aut-sei=Honda en-aut-mei=Mitsugi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HayashiAiko en-aut-sei=Hayashi en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HasegawaKoshi en-aut-sei=Hasegawa en-aut-mei=Koshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KidaKatsuhiro en-aut-sei=Kida en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=GotoSachiko en-aut-sei=Goto en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Radiology, Hiroshima University Hospital kn-affil= affil-num=9 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical, Okayama University kn-affil= en-keyword=Image quality kn-keyword=Image quality en-keyword=photon-counting computed tomography kn-keyword=photon-counting computed tomography en-keyword=quantum iterative reconstruction kn-keyword=quantum iterative reconstruction en-keyword=radiomics kn-keyword=radiomics en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=10462 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250326 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) is believed to possess immune evasion capabilities, but it remains unclear whether this immune evasion is related to host gene alternative splicing (AS). In this study, RNA-sequencing revealed significant changes in both AS landscape and transcriptomic profile of macrophages following P. gingivalis infection with/without knockout of gingipain (a unique toxic protease of P. gingivalis). P. gingivalis infection increased the PD-L1 transcripts expression and selectively upregulated a specific coding isoform that more effectively binds to PD-1 on T cells, thereby inhibiting immune function. Biological experiments also detected AS switch of PD-L1 in P. gingivalis-infected or gingipain-treated macrophages. AlphaFold 3 predictions indicated that the protein docking compatibility between PD-1 and P. gingivalis-upregulated PD-L1 isoform was over 80% higher than another coding isoform. These findings suggest that P. gingivalis employs gingipain to modulate the AS of PD-L1, facilitating immune evasion. en-copyright= kn-copyright= en-aut-name=ZhengYilin en-aut-sei=Zheng en-aut-mei=Yilin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=WengYao en-aut-sei=Weng en-aut-mei=Yao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SitosariHeriati en-aut-sei=Sitosari en-aut-mei=Heriati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HeYuhan en-aut-sei=He en-aut-mei=Yuhan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhangXiu en-aut-sei=Zhang en-aut-mei=Xiu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShiotsuNoriko en-aut-sei=Shiotsu en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukuharaYoko en-aut-sei=Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= affil-num=1 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=7 en-affil=Comprehensive Dental Clinic, Okayama University Hospital, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=Gingipain kn-keyword=Gingipain en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Alternative splicing kn-keyword=Alternative splicing en-keyword=PD-L1 kn-keyword=PD-L1 en-keyword=Immune evasion kn-keyword=Immune evasion END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue=3 article-no= start-page=033907 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of density measurement at high pressure and high temperature using the x-ray absorption method combined with laser-heated diamond anvil cell en-subtitle= kn-subtitle= en-abstract= kn-abstract=The densities of liquid materials at high pressures and high temperatures are important information to understand the elastic behavior of liquids at extreme conditions, which is closely related to the formation and evolution processes of the Earth and planetary interiors. The x-ray absorption method is an effective method to measure the density of non-crystalline materials at high pressures. However, the temperature condition of the x-ray absorption method using a diamond anvil cell (DAC) has been limited to 720 K to date. To significantly expand the measurable temperature condition of this method, in this study, we developed a density measurement technique using the x-ray absorption method in combination with a laser-heated DAC. The density of solid Ni was measured up to 26 GPa and 1800 K using the x-ray absorption method and evaluated by comparison with the density obtained from the x-ray diffraction. The density of solid Ni with a thickness >17 μm was determined with an accuracy of 0.01%?2.2% (0.001?0.20 g/cm3) and a precision of 0.8%?1.8% (0.07?0.16 g/cm3) in the x-ray absorption method. The density of liquid Ni was also determined to be 8.70 ± 0.15?8.98 ± 0.38 g/cm3 at 16?23 GPa and 2230?2480 K. Consequently, the temperature limit of the x-ray absorption method can be expanded from 720 to 2480 K by combining it with a laser-heated DAC in this study. en-copyright= kn-copyright= en-aut-name=TerasakiHidenori en-aut-sei=Terasaki en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KaminaHiroyuki en-aut-sei=Kamina en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaguchiSaori I. en-aut-sei=Kawaguchi en-aut-mei=Saori I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTadashi en-aut-sei=Kondo en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriokaKo en-aut-sei=Morioka en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsuruokaRyo en-aut-sei=Tsuruoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakuraiMoe en-aut-sei=Sakurai en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YonedaAkira en-aut-sei=Yoneda en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KamadaSeiji en-aut-sei=Kamada en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiraoNaohisa en-aut-sei=Hirao en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=3 en-affil=Japan Synchrotron Radiation Research Institute, SPring-8 kn-affil= affil-num=4 en-affil=Department of Earth and Space Science, Osaka University kn-affil= affil-num=5 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Earth and Space Science, Osaka University kn-affil= affil-num=7 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Earth and Space Science, Osaka University kn-affil= affil-num=9 en-affil=AD Science Incorporation kn-affil= affil-num=10 en-affil=Japan Synchrotron Radiation Research Institute, SPring-8 kn-affil= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=6 article-no= start-page=2485 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vesicular Glutamate Transporter 3 Is Involved in Glutamatergic Signalling in Podocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glomerular podocytes act as a part of the filtration barrier in the kidney. The activity of this filter is regulated by ionotropic and metabotropic glutamate receptors. Adjacent podocytes can potentially release glutamate into the intercellular space; however, little is known about how podocytes release glutamate. Here, we demonstrated vesicular glutamate transporter 3 (VGLUT3)-dependent glutamate release from podocytes. Immunofluorescence analysis revealed that rat glomerular podocytes and an immortal mouse podocyte cell line (MPC) express VGLUT1 and VGLUT3. Consistent with this finding, quantitative RT-PCR revealed the expression of VGLUT1 and VGLUT3 mRNA in undifferentiated and differentiated MPCs. In addition, the exocytotic proteins vesicle-associated membrane protein 2, synapsin 1, and synaptophysin 1 were present in punctate patterns and colocalized with VGLUT3 in MPCs. Interestingly, approximately 30% of VGLUT3 colocalized with VGLUT1. By immunoelectron microscopy, VGLUT3 was often observed around clear vesicle-like structures in differentiated MPCs. Differentiated MPCs released glutamate following depolarization with high potassium levels and after stimulation with the muscarinic agonist pilocarpine. The depletion of VGLUT3 in MPCs by RNA interference reduced depolarization-dependent glutamate release. These results strongly suggest that VGLUT3 is involved in glutamatergic signalling in podocytes and may be a new drug target for various kidney diseases. en-copyright= kn-copyright= en-aut-name=NishiiNaoko en-aut-sei=Nishii en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiTomoko en-aut-sei=Kawai en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuokaHiroki en-aut-sei=Yasuoka en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeTadashi en-aut-sei=Abe en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TatsumiNanami en-aut-sei=Tatsumi en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaradaYuika en-aut-sei=Harada en-aut-mei=Yuika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyajiTakaaki en-aut-sei=Miyaji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LiShunai en-aut-sei=Li en-aut-mei=Shunai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsukanoMoemi en-aut-sei=Tsukano en-aut-mei=Moemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OgawaDaisuke en-aut-sei=Ogawa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakeiKohji en-aut-sei=Takei en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cell Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University kn-affil= affil-num=7 en-affil=Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University kn-affil= affil-num=8 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Central Research Laboratory, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=VGLUT3 kn-keyword=VGLUT3 en-keyword=glutamate kn-keyword=glutamate en-keyword=podocyte kn-keyword=podocyte en-keyword=glutamatergic transmission kn-keyword=glutamatergic transmission END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue= article-no= start-page=1547222 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=Interleukin-6/soluble IL-6 receptor-induced secretion of cathepsin B and L from human gingival fibroblasts is regulated by caveolin-1 and ERK1/2 pathways en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Cathepsins are essential lysosomal enzymes that maintain organismal homeostasis by degrading extracellular substrates. The inflammatory cytokine interleukin-6 (IL-6) increases the production of cathepsins through the caveolin-1 (Cav-1) and c-Jun N-terminal kinase (JNK) signaling pathways, which have been implicated in the destruction of periodontal tissue. This study investigated the effect of the IL-6/soluble IL-6 receptor (sIL-6R) complex on the extracellular secretion of cathepsins in human gingival fibroblasts (HGFs) and examined the function of extracellularly secreted cathepsins B and L under acidic culture conditions in vitro.
Methods: HGFs were isolated from healthy volunteer donors. The expression of Cav-1 was suppressed via transfection with small interfering RNA (siRNA) targeting Cav-1. The expression levels of cathepsins B and L induced by extracellular IL-6/sIL-6R were measured using western blotting and enzyme-linked immunosorbent assay. Extracellular cathepsin activity following IL-6/sIL-6R stimulation was assessed using a methylcoumarylamide substrate in a fluorescence-based assay. IL-6/sIL-6R-induced expression of cathepsins B and L in HGFs was quantified under inhibitory conditions for extracellular signal-regulated kinase (ERK) 1/2 and/or JNK signaling, both of which are transduction pathways activated by IL-6/sIL-6R. This quantification was also performed in HGFs with suppressed Cav-1 expression using western blotting.
Results: Cathepsins B and L were secreted in their precursor forms from HGFs, with significantly elevated protein levels observed at 24, 48, and 72 h post-IL-6/sIL-6R stimulation. Under acidic culture conditions, cathepsin B activity increased at 48 and 72 h. Cav-1 suppression inhibited the secretion of cathepsin B regardless of IL-6/sIL-6R stimulation, whereas the secretion of cathepsin L was reduced only after 48 h of IL-6/sIL-6R stimulation. Inhibition of ERK1/2 and JNK pathways decreased the secretion of cathepsin B after 48 h of IL-6/sIL-6R stimulation, and JNK inhibition reduced the secretion of cathepsin L under similar conditions.
Conclusion: IL-6/sIL-6R stimulation increased the extracellular secretion of cathepsin B and L precursors in HGFs, and these precursors became activated under acidic conditions. Cav-1 and ERK1/2 are involved in regulating the secretion of cathepsin B precursors. en-copyright= kn-copyright= en-aut-name=GotoAyaka en-aut-sei=Goto en-aut-mei=Ayaka 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=Yamaguchi-TomikawaTomoko en-aut-sei=Yamaguchi-Tomikawa en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiHiroya en-aut-sei=Kobayashi en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 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, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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 Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Periodontics & Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cathepsin B kn-keyword=cathepsin B en-keyword=cathepsin L kn-keyword=cathepsin L en-keyword=human gingival fibroblast kn-keyword=human gingival fibroblast en-keyword=interleukin-6 kn-keyword=interleukin-6 en-keyword=caveolin kn-keyword=caveolin END start-ver=1.4 cd-journal=joma no-vol=301 cd-vols= no-issue=4 article-no= start-page=108334 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of basic amino acid residues in substrate binding and transport of the light-driven anion pump Synechocystis halorhodopsin (SyHR) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Microbial rhodopsins are photoreceptive seventransmembrane a-helical proteins, many of which function as ion transporters, primarily for small monovalent ions such as Na+, K+, Cl-, Br-, and I-. Synechocystis halorhodopsin (SyHR), identified from the cyanobacterium Synechocystis sp. PCC 7509, uniquely transports the polyatomic divalent SO42- inward, in addition to monovalent anions (Cl- and Br-). In this study, we conducted alanine-scanning mutagenesis on twelve basic amino acid residues to investigate the anion transport mechanism of SyHR. We quantitatively evaluated the Cl-and SO42- transport activities of the WT SyHR and its mutants. The results showed a strong correlation between the Cl-and SO42- transport activities among them (R = 0.94), suggesting a shared pathway for both anions. Notably, the R71A mutation selectively abolished SO42- transport activity while maintaining Cl- transport, whereas the H167A mutation significantly impaired both Cl-and SO42- transport. Furthermore, spectroscopic analysis revealed that the R71A mutant lost its ability to bind SO42- due to the absence of a positive charge, while the H167A mutant failed to accumulate the O intermediate during the photoreaction cycle (photocycle) due to reduced hydrophilicity. Additionally, computational analysis revealed the SO42- binding modes and clarified the roles of residues involved in its binding around the retinal chromophore. Based on these findings and previous structural information, we propose that the positive charge and hydrophilicity of Arg71 and His167 are crucial for the formation of the characteristic initial and transient anion-binding site of SyHR, enabling its unique ability to bind and transport both Cl-and SO42-. en-copyright= kn-copyright= en-aut-name=NakamaMasaki en-aut-sei=Nakama en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NojiTomoyasu en-aut-sei=Noji en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshizawaSusumu en-aut-sei=Yoshizawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshikitaHiroshi en-aut-sei=Ishikita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=microbial rhodopsin kn-keyword=microbial rhodopsin en-keyword=anion transport kn-keyword=anion transport en-keyword=retinal kn-keyword=retinal en-keyword=membrane protein kn-keyword=membrane protein en-keyword=photobiology kn-keyword=photobiology END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=6 article-no= start-page=2713 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Involvement of a Novel Variant of FGFR1 Detected in an Adult Patient with Kallmann Syndrome in Regulation of Gonadal Steroidogenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fibroblast growth factor receptor 1 (FGFR1), also known as KAL2, is a tyrosine kinase receptor, and variants of FGFR1 have been detected in patients with Kallmann syndrome (KS), which is a congenital developmental disorder characterized by central hypogonadism and anosmia. Herein, we report an adult case of KS with a novel variant of FGFR1. A middle-aged male was referred for a compression fracture of a lumbar vertebra. It was shown that he had severe osteoporosis, anosmia, gynecomastia, and a past history of operations for cryptorchidism. Endocrine workup using pituitary and gonadal stimulation tests revealed the presence of both primary and central hypogonadism. Genetic testing revealed a novel variant of FGFR1 (c.2197_2199dup, p.Met733dup). To identify the pathogenicity of the novel variant and the clinical significance for the gonads, we investigated the effects of the FGFR1 variant on the downstream signaling of FGFR1 and gonadal steroidogenesis by using human steroidogenic granulosa cells. It was revealed that the transfection of the variant gene significantly impaired FGFR1 signaling, detected through the downregulation of SPRY2, compared with that of the case of the forced expression of wild-type FGFR1, and that the existence of the variant gene apparently altered the expression of key steroidogenic factors, including StAR and aromatase, in the gonad. The results suggested that the novel variant of FGFR1 detected in the patient with KS was linked to the impairment of FGFR1 signaling, as well as the alteration of gonadal steroidogenesis, leading to the pathogenesis of latent primary hypogonadism. en-copyright= kn-copyright= en-aut-name=SoejimaYoshiaki en-aut-sei=Soejima en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaguchiMarina en-aut-sei=Kawaguchi en-aut-mei=Marina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoKoichiro en-aut-sei=Yamamoto en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasudaMiho en-aut-sei=Yasuda en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UedaKeigo en-aut-sei=Ueda en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwataNahoko en-aut-sei=Iwata en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=fibroblast growth factor receptor 1 (FGFR1) kn-keyword=fibroblast growth factor receptor 1 (FGFR1) en-keyword=gynecomastia kn-keyword=gynecomastia en-keyword=Kallmann syndrome (KS) kn-keyword=Kallmann syndrome (KS) en-keyword=osteoporosis and steroidogenesis kn-keyword=osteoporosis and steroidogenesis END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1537615 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=PARylation-mediated post-transcriptional modifications in cancer immunity and immunotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Poly-ADP-ribosylation (PARylation) is a post-translational modification in which ADP-ribose is added to substrate proteins. PARylation is mediated by a superfamily of ADP-ribosyl transferases known as PARPs and influences a wide range of cellular functions, including genome integrity maintenance, and the regulation of proliferation and differentiation. We and others have recently reported that PARylation of SH3 domain-binding protein 2 (3BP2) plays a role in bone metabolism, immune system regulation, and cytokine production. Additionally, PARylation has recently gained attention as a target for cancer treatment. In this review, we provide an overview of PARylation, its involvement in several signaling pathways related to cancer immunity, and the potential of combination therapies with PARP inhibitors and immune checkpoint inhibitors. en-copyright= kn-copyright= en-aut-name=MatsumotoKazuya en-aut-sei=Matsumoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=PARylation kn-keyword=PARylation en-keyword=cancer kn-keyword=cancer en-keyword=post-transcriptional regulation kn-keyword=post-transcriptional regulation en-keyword=ubiquitylation kn-keyword=ubiquitylation en-keyword=immune system kn-keyword=immune system END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=6 article-no= start-page=790 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250320 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Improving Diagnostic Performance for Head and Neck Tumors with Simple Diffusion Kurtosis Imaging and Machine Learning Bi-Parameter Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Mean kurtosis (MK) values in simple diffusion kurtosis imaging (SDI)-a type of diffusion kurtosis imaging (DKI)-have been reported to be useful in the diagnosis of head and neck malignancies, for which pre-processing with smoothing filters has been reported to improve the diagnostic accuracy. Multi-parameter analysis using DKI in combination with other image types has recently been reported to improve the diagnostic performance. The purpose of this study was to evaluate the usefulness of machine learning (ML)-based multi-parameter analysis using the MK and apparent diffusion coefficient (ADC) values-which can be acquired simultaneously through SDI-for the differential diagnosis of benign and malignant head and neck tumors, which is important for determining the treatment strategy, as well as examining the usefulness of filter pre-processing. Methods: A total of 32 pathologically diagnosed head and neck tumors were included in the study, and a Gaussian filter was used for image pre-processing. MK and ADC values were extracted from pixels within the tumor area and used as explanatory variables. Five ML algorithms were used to create models for the prediction of tumor status (benign or malignant), which were evaluated through ROC analysis. Results: Bi-parameter analysis with gradient boosting achieved the best diagnostic performance, with an AUC of 0.81. Conclusions: The usefulness of bi-parameter analysis with ML methods for the differential diagnosis of benign and malignant head and neck tumors using SDI data were demonstrated. en-copyright= kn-copyright= en-aut-name=YoshidaSuzuka en-aut-sei=Yoshida en-aut-mei=Suzuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaMasahiro en-aut-sei=Kuroda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraYoshihide en-aut-sei=Nakamura en-aut-mei=Yoshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukumuraYuka en-aut-sei=Fukumura en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamitsuYuki en-aut-sei=Nakamitsu en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Al-HammadWlla E. en-aut-sei=Al-Hammad en-aut-mei=Wlla E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaKazuhiro en-aut-sei=Kuroda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuYudai en-aut-sei=Shimizu en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=OitaMasataka en-aut-sei=Oita en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SugiantoIrfan en-aut-sei=Sugianto en-aut-mei=Irfan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=BarhamMajd en-aut-sei=Barham en-aut-mei=Majd kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TekikiNouha en-aut-sei=Tekiki en-aut-mei=Nouha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KamaruddinNurul N. en-aut-sei=Kamaruddin en-aut-mei=Nurul N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 ORCID= en-aut-name=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University kn-affil= affil-num=12 en-affil=Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National University kn-affil= affil-num=13 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=head and neck tumors kn-keyword=head and neck tumors en-keyword=mean kurtosis kn-keyword=mean kurtosis en-keyword=simple diffusion kurtosis imaging kn-keyword=simple diffusion kurtosis imaging en-keyword=magnetic resonance imaging kn-keyword=magnetic resonance imaging en-keyword=apparent diffusion coefficient value kn-keyword=apparent diffusion coefficient value en-keyword=diffusion kurtosis imaging kn-keyword=diffusion kurtosis imaging en-keyword=machine learning kn-keyword=machine learning en-keyword=bi-parameter analysis kn-keyword=bi-parameter analysis en-keyword=gradient boosting kn-keyword=gradient boosting en-keyword=differential diagnosis of benign and malignant kn-keyword=differential diagnosis of benign and malignant END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=e70053 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250323 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of blood carboxyhemoglobin levels with mortality and neurological outcomes in out-of-hospital cardiac arrest en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Carbon monoxide (CO), produced endogenously by heme oxygenase-1, plays a crucial role in the immune system by mitigating cellular damage under stress. However, the significance of carboxyhemoglobin (COHb) levels after out-of-hospital cardiac arrest (OHCA) is not well understood. This study aimed to explore the association between COHb levels at hospital arrival and within the first 24 h post-arrival with 30-day mortality and neurological outcomes in patients who experienced OHCA.
Methods: This single-center, retrospective study analyzed data from adult patients who experienced OHCA seen at Okayama University Hospital from 2019 to 2023. The patients were assigned to one of two study groups based on COHb levels (0.0% or >= 0.1%) upon hospital arrival. The primary outcome was 30-day mortality.
Results: Among the 560 eligible patients who experienced OHCA, 284 (50.7%) were in the COHb 0.0% group and 276 (49.3%) were in the COHb >= 0.1% group. The 30-day mortality was significantly higher in the COHb 0.0% group compared to the COHb >= 0.1% group (264 [92.9%] vs. 233 [84.4%]). Multivariable logistic regression showed that the COHb 0.0% group was associated with 30-day mortality (adjusted ORs: 2.24, 95% CIs: 1.10-4.56). Non-survivors at 30 days who were admitted to the intensive care unit had lower COHb levels at hospital arrival (0.0% vs. 0.2%) and lower mean COHb levels during the first 24 h post-arrival (0.7% vs. 0.9%) compared to survivors.
Conclusions: COHb levels of 0.0% were linked to worse outcomes in patients experiencing OHCA, warranting further research on the prognostic implications of COHb in this context. 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=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiraokaTomohiro en-aut-sei=Hiraoka en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiYuya en-aut-sei=Murakami en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Emergency, 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, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=brain injury kn-keyword=brain injury en-keyword=carbon monoxide kn-keyword=carbon monoxide en-keyword=carboxyhemoglobin kn-keyword=carboxyhemoglobin en-keyword=cardiac arrest kn-keyword=cardiac arrest en-keyword=resuscitation kn-keyword=resuscitation END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=6 article-no= start-page=619 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250313 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Trehalose on Halitosis: A Randomized Cross-Over Clinical Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Halitosis is a condition characterized by an unpleasant malodor. Intra-oral halitosis is caused by volatile sulfur compounds (VSCs) and can be associated with oral dryness. Trehalose is one of the materials used to relieve oral dryness. The aim of the present study was to investigate the effect of trehalose on halitosis. Methods: This prospective, double-blinded, placebo-controlled, cross-over study enrolled volunteers from Okayama University Hospital. The participants were randomly divided into two groups, with one group receiving trehalose (a 10% trehalose solution) and the other receiving a placebo (distilled water) in a 1:1 allocation. The primary study outcome was the subjective organoleptic test. The secondary outcomes were the concentrations of the VSCs, which were measured using a portable gas chromatography device, and the oral moisture status, which was measured using an oral moisture meter. The planned sample size was 10 participants based on the previous study. Results: The final intention-to-treat analysis was performed using the data from 9 participants. After applying 10% trehalose as an oral spray, the organoleptic score decreased in a time-dependent manner. However, no significant differences were seen between the trehalose and placebo groups. In terms of secondary outcomes, the oral moisture levels increased immediately after the trehalose spray application, and significant differences in the amount of change from the baseline were seen between the trehalose and placebo groups (p = 0.047). No significant differences were seen in any of the other variables (p > 0.05). Conclusions: We could not identify any positive effects on halitosis from a one-time 10% trehalose application as an oral spray in this prospective, double-blinded, placebo-controlled, cross-over study. However, the trehalose application immediately improved the oral moisture levels and was useful for treating oral dryness. en-copyright= kn-copyright= en-aut-name=MiyaiHisataka en-aut-sei=Miyai en-aut-mei=Hisataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TomofujiTakaaki en-aut-sei=Tomofuji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MizunoHirofumi en-aut-sei=Mizuno en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakaharaMomoko en-aut-sei=Nakahara en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KataokaKota en-aut-sei=Kataoka en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SumitaIchiro en-aut-sei=Sumita en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchidaYurika en-aut-sei=Uchida en-aut-mei=Yurika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyamaNaoki en-aut-sei=Toyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YokoiAya en-aut-sei=Yokoi en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Yamanaka-KohnoReiko en-aut-sei=Yamanaka-Kohno en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakeuchiNoriko en-aut-sei=Takeuchi en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Community Oral Health, School of Dentistry, Asahi University kn-affil= affil-num=3 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=halitosis kn-keyword=halitosis en-keyword=trehalose kn-keyword=trehalose en-keyword=oral dryness kn-keyword=oral dryness en-keyword=cross-over study kn-keyword=cross-over study en-keyword=randomized trial kn-keyword=randomized trial END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3 article-no= start-page=e81476 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250330 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Natural Course From Primary Intraocular Lymphoma to Brain Lymphoma in Four Years According to Patient's Choice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary intraocular lymphoma or vitreoretinal lymphoma is a rare entity of diffuse large B-cell lymphoma that presents vitreous opacity and retinal and choroidal infiltration. Primary central nervous system lymphoma would occur previously, later, or concurrently with respect to primary intraocular lymphoma. This study reported a 72-year-old patient with a pathological diagnosis of primary intraocular lymphoma who developed central nervous system lymphoma four years later in the course of no treatment. She presented with a four-year history of blurred vision in both eyes after cataract surgeries. Three weeks previously, she underwent a vitrectomy in the left eye at a clinic, and measurements of the vitreous fluid showed a high level of interleukin-10 at 5739 pg/mL, in contrast with interleukin-6 at 142 pg/mL. Cytology of the vitreous fluid was class III on the Papanicolaou classification. Head magnetic resonance imaging detected nothing abnormal. She underwent vitrectomy in the right eye as a diagnostic procedure to show large cells in the vitreous which were positive for CD20 and Ki-67 and negative for CD3, leading to a pathological diagnosis of large B-cell lymphoma. Prophylactic chemotherapy with high-dose methotrexate was recommended as a therapeutic option, but she chose observation since she did not have any eye or systemic symptoms. In the follow-up every three months by an oncologist and an ophthalmologist, she did not have any symptoms, and serum levels of soluble interleukin-2 receptor were in the normal range at each visit. She was well for four years until the age of 76 years when she fell and hit her head, and an emergency head computed tomography scan showed a mass in the left occipital lobe. Magnetic resonance imaging demonstrated a well-defined circular mass in the left occipital lobe with a hyperintense signal in the T2-weighted fluid-attenuated inversion recovery (FLAIR) image and diffusion-weighted image. Fluorodeoxyglucose positron emission tomography showed no abnormal uptake systemically, except for the left occipital lesion. She underwent a brain biopsy by craniotomy to pathologically prove diffuse large B-cell lymphoma. She was recommended to receive first-line chemotherapy as the standard treatment but chose observation with no treatment and died of brain lymphoma nine months later. This case happened to illustrate a natural course of primary intraocular lymphoma which proceeded to central nervous system lymphoma four years later. 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=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoShotaro en-aut-sei=Kondo en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Kurashiki Municipal Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=brain biopsy kn-keyword=brain biopsy en-keyword=cell block pathology kn-keyword=cell block pathology en-keyword=diffuse large b-cell lymphoma kn-keyword=diffuse large b-cell lymphoma en-keyword=natural course kn-keyword=natural course en-keyword=primary central nervous system lymphoma kn-keyword=primary central nervous system lymphoma en-keyword=primary intraocular (vitreoretinal) lymphoma kn-keyword=primary intraocular (vitreoretinal) lymphoma en-keyword=vitrectomy kn-keyword=vitrectomy en-keyword=vitreous opacity kn-keyword=vitreous opacity END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue= article-no= start-page=1551700 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acetoacetate, a ketone body, attenuates neuronal bursts in acutely-induced epileptiform slices of the mouse hippocampus en-subtitle= kn-subtitle= en-abstract= kn-abstract=The ketogenic diet increases ketone bodies (beta-hydroxybutyrate and acetoacetate) in the brain, and ameliorates epileptic seizures in vivo. However, ketone bodies exert weak or no effects on electrical activity in rodent hippocampal slices. Especially, it remains unclear what kinds of conditions are required to strengthen the actions of ketone bodies in hippocampal slices. In the present study, we examined the effects of acetoacetate on hippocampal pyramidal cells in normal slices and epileptiform slices of mice. By using patch-clamp recordings from CA1 pyramidal cells, we first confirmed that acetoacetate did not change the membrane potentials and intrinsic properties of pyramidal cells in normal slices. However, we found that acetoacetate weakened spontaneous epileptiform bursts in pyramidal cells of epileptiform slices, which were acutely induced by applying convulsants to normal slices. Interestingly, acetoacetate did not change the frequency of the epileptiform bursts, but attenuated individual epileptiform bursts. We finally examined the effects of acetoacetate on excitatory synaptic barrages during epileptiform activity, and found that acetoacetate weakened epileptiform bursts by reducing synchronous synaptic inputs. These results show that acetoacetate attenuated neuronal bursts in epileptiform slices, but did not affect neuronal activity in normal slices, which leads to seizure-selective actions of ketone bodies. en-copyright= kn-copyright= en-aut-name=WenHao en-aut-sei=Wen en-aut-mei=Hao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SadaNagisa en-aut-sei=Sada en-aut-mei=Nagisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueTsuyoshi en-aut-sei=Inoue en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=epilepsy kn-keyword=epilepsy en-keyword=ketone body kn-keyword=ketone body en-keyword=ketogenic diet kn-keyword=ketogenic diet en-keyword=hippocampus kn-keyword=hippocampus en-keyword=slice physiology kn-keyword=slice physiology en-keyword=patch-clamp recording kn-keyword=patch-clamp recording END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=3-4 article-no= start-page=362 end-page=314 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=2024 General Election in Britain: an Analysis of BES 2014-2024 Internet Panel Data kn-title=2024年イギリス総選挙：BES 2014-2024 Internet Panel Data の分析 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NarihiroT. en-aut-sei=Narihiro en-aut-mei=T. kn-aut-name=成廣孝 kn-aut-sei=成廣 kn-aut-mei=孝 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学学術研究院社会文化科学学域 END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=3-4 article-no= start-page=189 end-page=252 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Les extinctions des droits r?els grev?s sur l’immeuble qui est acquis par usucapion : La recherche historique sur la jurisprudence au XIXe si?cle. kn-title=所有権の時効取得と他物権の帰趨 ― 一九世紀フランス法の議論構造に照らして― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ShimazuG. en-aut-sei=Shimazu en-aut-mei=G. kn-aut-name=嶋津元 kn-aut-sei=嶋津 kn-aut-mei=元 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学学術研究院社会文化科学学域 END start-ver=1.4 cd-journal=joma no-vol=85 cd-vols= no-issue=6 article-no= start-page=1082 end-page=1096 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250314 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Brain metastasis is a poor prognostic factor in patients with cancer. Despite showing efficacy in many extracranial tumors, immunotherapy with anti?PD-1 mAb or anti?CTLA4 mAb seems to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti?PD-1 and anti?CTLA4 mAbs has a potent antitumor effect on brain metastasis, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. In this study, we analyzed the tumor-infiltrating lymphocytes in murine models of brain metastasis that responded to anti?CTLA4 and anti?PD-1 mAbs. Activated CD4+ T follicular helper (TFH) cells with high CTLA4 expression characteristically infiltrated the intracranial TME, which were activated by combination anti?CTLA4 and anti?PD-1 treatment. The loss of TFH cells suppressed the additive effect of CTLA4 blockade on anti?PD-1 mAb. B-cell?activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo proinflammatory M1-like macrophages, in the intracranial TME induced B-cell and TFH-cell infiltration and activation. Furthermore, the intracranial TME of patients with non?small cell lung cancer featured TFH- and B-cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell cross-talk in the intracranial TME that facilitates an additive antitumor effect of CTLA4 blockade with anti?PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for brain metastases.
Significance: B-cell and CD4+ T follicular helper cell activation via BAFF/APRIL from abundant myeloid cells in the intracranial tumor microenvironment enables a combinatorial effect of CTLA4 and PD-1 blockade in brain metastases. en-copyright= kn-copyright= en-aut-name=NinomiyaToshifumi en-aut-sei=Ninomiya en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MukoharaFumiaki en-aut-sei=Mukohara en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyamotoAi en-aut-sei=Miyamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=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= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OkamotoIsamu en-aut-sei=Okamoto en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Medical Protein Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=18 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=1 article-no= start-page=2480231 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=Specific enhancement of the translation of thermospermine-responsive uORF-containing mRNAs by ribosomal mutations in Arabidopsis thaliana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Auxin-induced xylem formation in angiosperms is negatively regulated by thermospermine, whose biosynthesis is also induced by auxin. In Arabidopsis thaliana, loss-of-function mutants of ACL5, which encodes thermospermine synthase, exhibit a dwarf phenotype accompanied by excessive xylem formation. Studies of suppressor mutants that recover from the acl5 dwarf phenotype suggest that thermospermine alleviates the inhibitory effect of an upstream open-reading frame (uORF) on the main ORF translation of SAC51 mRNA. Many suppressor mutations for acl5 have been mapped to the uORF conserved in the SAC51 family or to ribosomal protein genes, such as RPL10A, RPL4A, and RACK1A. In this study, we identified newly isolated acl5 suppressors, sac501, sac504, and sac506, which are additional alleles of RPL10A and the uORFs of SAC51 family members, SACL1 and SACL3, respectively. To investigate whether acl5-suppressor alleles of ribosomal genes broadly affect translation of uORF-containing mRNAs, we examined GUS activity in several 5'-GUS fusion constructs. Our results showed that these alleles enhanced GUS activity in SAC51 and SACL3 5'-fusion constructs but had no effect on other 5'-fusion constructs unrelated to thermospermine response. This suggests that these ribosomal proteins are specifically involved in the thermospermine-mediated regulation of mRNA translation. en-copyright= kn-copyright= en-aut-name=MutsudaKoki en-aut-sei=Mutsuda en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiiYuichi en-aut-sei=Nishii en-aut-mei=Yuichi 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=FukushimaHiroko en-aut-sei=Fukushima en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=mRNA translation kn-keyword=mRNA translation en-keyword=RPL10 kn-keyword=RPL10 en-keyword=suppressor mutant kn-keyword=suppressor mutant en-keyword=thermospermine kn-keyword=thermospermine en-keyword=uORF kn-keyword=uORF END start-ver=1.4 cd-journal=joma no-vol=43-45 cd-vols= no-issue= article-no= start-page=15 end-page=28 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=試験研究 : 2020〜2022年度 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=8502 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Age-specific assessment of initial hemoglobin levels and shock index for predicting life-saving interventions in pediatric blunt liver and spleen injuries en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to evaluate the effectiveness of combining initial hemoglobin levels with the shock index for predicting the need for life-saving interventions (LSI) in pediatric patients with blunt liver and spleen injuries (BLSI), specifically tailored to different age groups. This was a multicenter retrospective cohort study of pediatric patients with BLSI in Japan. The area under the receiver operating characteristic curve (AUROC) were used to assess predictive accuracy. The study included 1,370 patients. LSI was required in 59 of 247 (23.9%) aged 1 to 6 years, 100 of 402 (24.9%) aged 7 to 12 years, and 125 of 297 (42.1%) patients aged 13 to 16 years. Within each specific age group, the predictability was categorized as fair and appeared higher than that of the entire cohort or when using either parameter alone. Notably, in the 1 to 6-year age group, the combined values showed the highest predictability, which was statistically superior to the shock index alone (AUROC of 0.770 vs. 0.671, P = 0.025). Tailoring initial hemoglobin levels and shock index to specific age groups enhances predictability of LSI in pediatric BLSI, showing a fair level of predictive accuracy. en-copyright= kn-copyright= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya 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=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IidaAtsuyoshi en-aut-sei=Iida en-aut-mei=Atsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=KatsuraMorihiro en-aut-sei=Katsura en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KondoYutaka en-aut-sei=Kondo en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YasudaHideto en-aut-sei=Yasuda en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KushimotoShigeki en-aut-sei=Kushimoto en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=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= en-aut-name=SHIPPs Study Group en-aut-sei=SHIPPs Study Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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 Surgery, Okinawa Chubu Hospital kn-affil= affil-num=7 en-affil=Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital kn-affil= affil-num=8 en-affil=Department of Emergency and Critical Care Medicine, Jichi Medical University Saitama Medical Center kn-affil= affil-num=9 en-affil=Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil= kn-affil= en-keyword=Abdominal injuries kn-keyword=Abdominal injuries en-keyword=Blood transfusions kn-keyword=Blood transfusions en-keyword=Hemoglobin kn-keyword=Hemoglobin en-keyword=Hemostasis kn-keyword=Hemostasis en-keyword=Shock index kn-keyword=Shock index END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=1757 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Keratinocyte-driven dermal collagen formation in the axolotl skin en-subtitle= kn-subtitle= en-abstract= kn-abstract=Type I collagen is a major component of the dermis and is formed by dermal fibroblasts. The development of dermal collagen structures has not been fully elucidated despite the major presence and importance of the dermis. This lack of understanding is due in part to the opacity of mammalian skin and it has been an obstacle to cosmetic and medical developments. We reveal the process of dermal collagen formation using the highly transparent skin of the axolotl and fluorescent collagen probes. We clarify that epidermal cells, not dermal fibroblasts, contribute to dermal collagen formation. Mesenchymal cells (fibroblasts) play a role in modifying the collagen fibers already built by keratinocytes. We confirm that collagen production by keratinocytes is a widely conserved mechanism in other model organisms. Our findings warrant a change in the current consensus about dermal collagen formation and could lead to innovations in cosmetology and skin medication. en-copyright= kn-copyright= en-aut-name=OhashiAyaka en-aut-sei=Ohashi en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurodaJunpei en-aut-sei=Kuroda en-aut-mei=Junpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoYohei en-aut-sei=Kondo en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KameiYasuhiro en-aut-sei=Kamei en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NonakaShigenori en-aut-sei=Nonaka en-aut-mei=Shigenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FurukawaSaya en-aut-sei=Furukawa en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoSakiya en-aut-sei=Yamamoto en-aut-mei=Sakiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Frontier Biosciences, Osaka University kn-affil= affil-num=4 en-affil=Center for One Medicine Innovative Translational Research (COMIT), Nagoya University kn-affil= affil-num=5 en-affil=Laboratory for Biothermology, National Institute for Basic Biology kn-affil= affil-num=6 en-affil=The Graduate University for Advanced Studies (SOKENDAI) kn-affil= affil-num=7 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=7506 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A glucocorticoid-regulating molecule, Fkbp5, may interact with mitogen-activated protein kinase signaling in the organ of Corti of mice cochleae en-subtitle= kn-subtitle= en-abstract= kn-abstract=FKBP5 is a 51-Da FK506-binding protein and member of the immunophilin family involved in controlling the signaling of glucocorticoid receptor from the cytosol to nucleus. Fkbp5 has previously been shown to be expressed in murine cochlear tissue, including the organ of Corti (i.e., the sensory epithelium of the cochlea). Fkbp5-/- mice as used in this study show hearing loss in the low-frequency (8-kHz) range and click-evoked auditory brainstem response (ABR) threshold compared to wild-type mice. Both Fkbp5-/- and wild-type mice showed hearing loss at all frequencies and click-ABR thresholds at 24 h and 14 days following acoustic overexposure (AO). Tissues of the organ of Corti were subjected to RNA sequencing and KEGG pathway analysis. In Fkbp5-/- mice before AO, the mitogen-activated protein kinase (MAPK) signaling pathway was dysregulated compared to wild-type mice. In wild-type mice at 12 h following AO, the most significantly modulated KEGG pathway was the TNF signaling pathway and major MAPK molecules p38 and Jun were involved in the TNF signaling pathway. In Fkbp5-/- mice at 12 h following AO, the MAPK signaling pathway was dysregulated compared to wild-type mice following AO. In conclusion, Fkbp5 interacts with MAPK signaling in the organ of Corti in mice cochleae. en-copyright= kn-copyright= en-aut-name=SatoAsuka en-aut-sei=Sato en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MaedaYukihide en-aut-sei=Maeda en-aut-mei=Yukihide 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 Otolaryngology-Head and Neck Surgery, 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=The organ of Corti kn-keyword=The organ of Corti en-keyword=Acoustic trauma kn-keyword=Acoustic trauma en-keyword=RNA sequencing kn-keyword=RNA sequencing en-keyword=51-Da FK506-binding protein kn-keyword=51-Da FK506-binding protein en-keyword=Mitogen-activated protein kinase signaling kn-keyword=Mitogen-activated protein kinase signaling en-keyword=Tumor necrosis factor signaling kn-keyword=Tumor necrosis factor signaling END start-ver=1.4 cd-journal=joma no-vol=752 cd-vols= no-issue= article-no= start-page=151481 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Discovery of myeloid zinc finger (MZF) 1 nuclear bodies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Myeloid zinc finger 1 (MZF1) is a multifaceted transcription factor that can act either as a transcriptional activator or a gene repressor. We examined its production of nuclear bodies (NBs) and subcellular localization. Proteomic and protein?protein interaction analysis were used to identify its cofactors and interactions. These revealed the presence of MZF1-NBs (intranuclear oligomers containing MZF1). MZF-NBs are similar to some other nuclear bodies, notably promyelocytic leukemia (PML) -NBs in terms of size and morphology. However the two structures appear to be different. MZF-NBs and PML-NBs were found to associate in the nucleus. Both MZF1 and PML are SUMO1-SUMOylated in PC-3 cells. Sumoylated MZF1 can interact with proteins containing SUMO-interaction motifs (SIM) through SUMO-SIM interaction. Interactome analysis revealed that its NBs participate in the stress response (TPR and UBAP2L), protein folding (CALR and ANKRD40), transcription, post-translational modification (TRIM33, ACOT7, CAMK2D, and CAMK2G), and RNA binding (ALURBP and CPSF5). en-copyright= kn-copyright= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=Myeloid zinc finger 1 kn-keyword=Myeloid zinc finger 1 en-keyword=MZF1 kn-keyword=MZF1 en-keyword=Nuclear body kn-keyword=Nuclear body en-keyword=PML kn-keyword=PML en-keyword=Sumoylation kn-keyword=Sumoylation en-keyword=SCAN domain protein kn-keyword=SCAN domain protein END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue= article-no= start-page=1 end-page=60 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Annual report / Institute of Plant Science and Resources, Okayama University kn-title=岡山大学資源植物科学研究所報告 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Institute of Plant Science and Resources, Okayama University en-aut-sei=Institute of Plant Science and Resources, Okayama University en-aut-mei= kn-aut-name=岡山大学資源植物科学研究所 kn-aut-sei=岡山大学資源植物科学研究所 kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue= article-no= start-page=71 end-page=80 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250314 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=KIBITANGO : Development and Implementation of an Academic English Vocabulary Learning Program kn-title=きびたんご ―アカデミック英単語学習プログラムの開発と実践報告― en-subtitle= kn-subtitle= en-abstract=At Okayama University, we have developed and provided a self-study material called "Kibitango" to help students improve their academic English vocabulary. The project began in 2019, with a focus on collecting frequently used words from academic journals, resulting in a list of 1,500 words. Each word comes with explanations by project members and examples of how it is used in academic papers. The material has been available to students since the 2022 academic year. Registered students receive one word per day via email and learn through the Kibitango website. The number of users has steadily increased. Today, however, several challenges have emerged, including the need to update the word list and improve the delivery method and system. kn-abstract=岡山大学では学術英語の語彙力を伸ばすための自習教材として、「きびたんご」を開発し学生に提供している。2019年から開発のためのプロジェクトを開始し、学術雑誌から頻出単語を収集し1500語のリストを作成した。単語には意味・発音などの基礎情報以外に、プロジェクトメンバーによる解説や実際にどのように学術論文中に使用されているかの実例を付している。学生への提供は2022年度からで、登録した学生にメールで一日一単語配信し、専用ウェッブサイトで学習させるというシステムである。利用者も順調に増えている。開発開始から５年、提供から２年経過し、単語リストのアップデートや提供方法・システムの改善など課題も明らかになっている。 en-copyright= kn-copyright= en-aut-name=IGARASHIMasumi en-aut-sei=IGARASHI en-aut-mei=Masumi kn-aut-name=五十嵐潤美 kn-aut-sei=五十嵐 kn-aut-mei=潤美 aut-affil-num=1 ORCID= en-aut-name=OGINOMasaru en-aut-sei=OGINO en-aut-mei=Masaru kn-aut-name=荻野勝 kn-aut-sei=荻野 kn-aut-mei=勝 aut-affil-num=2 ORCID= en-aut-name=OTOSHIJunko en-aut-sei=OTOSHI en-aut-mei=Junko kn-aut-name=大年順子 kn-aut-sei=大年 kn-aut-mei=順子 aut-affil-num=3 ORCID= en-aut-name=TERANISHIMasako en-aut-sei=TERANISHI en-aut-mei=Masako kn-aut-name=寺西雅子 kn-aut-sei=寺西 kn-aut-mei=雅子 aut-affil-num=4 ORCID= en-aut-name=YOSHIDAAzumi en-aut-sei=YOSHIDA en-aut-mei=Azumi kn-aut-name=吉田安曇 kn-aut-sei=吉田 kn-aut-mei=安曇 aut-affil-num=5 ORCID= en-aut-name=KENMOTSUYoshi en-aut-sei=KENMOTSU en-aut-mei=Yoshi kn-aut-name=剱持淑 kn-aut-sei=剱持 kn-aut-mei=淑 aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute for Promotion of Education and Campus Life, Okayama University kn-affil=岡山大学教育推進機構 affil-num=2 en-affil=Institute for Promotion of Education and Campus Life, Okayama University kn-affil=岡山大学教育推進機構 affil-num=3 en-affil=Institute for Promotion of Education and Campus Life, Okayama University kn-affil=岡山大学教育推進機構 affil-num=4 en-affil=Institute for Promotion of Education and Campus Life, Okayama University kn-affil=岡山大学教育推進機構 affil-num=5 en-affil=Institute for Promotion of Education and Campus Life, Okayama University kn-affil=岡山大学教育推進機構 affil-num=6 en-affil=Institute for Promotion of Education and Campus Life, Okayama University kn-affil=岡山大学教育推進機構 en-keyword=学術語彙 kn-keyword=学術語彙 en-keyword=英語語彙力 kn-keyword=英語語彙力 en-keyword=自習教材 kn-keyword=自習教材 en-keyword=教材開発 kn-keyword=教材開発 END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=5 article-no= start-page=577 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of Oral Intake of Hydrogen-Rich Jelly Intake on Gingival Inflammation: A Double-Blind, Placebo-Controlled and Exploratory Randomized Clinical Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Initiation and progression of periodontal disease include oxidative stress. Systemic application of antioxidants may provide clinical benefits against periodontal disease including gingivitis. Recently, a jelly containing a high concentration of hydrogen (40 ppm) was developed. We hypothesized that oral intake of this hydrogen-rich jelly may be safe and effective on gingivitis. This clinical trial was designed to investigate the safety and efficacy of oral intake of hydrogen-rich jelly against gingival inflammation. Methods: Participants with gingivitis were instructed to orally ingest 30 g of hydrogen-rich jelly (experimental group) or placebo jelly (control group) three times a day for 14 consecutive days. The primary outcome of this trial was the percentage of bleeding on probing (BOP) sites. Secondary outcomes were oral parameters, serum reactive oxygen metabolites, antioxidant capacity, oxidative index, concentrations of cytokine (interleukin [IL]-1β, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha) in gingival crevicular fluid, and adverse events. For all parameters, Mann?Whitney U test was used for comparison between experimental and control groups. Analysis of covariance, controlling for baseline periodontal inflamed surface area, was performed to evaluate the association between the effect of the hydrogen-rich jelly and gingival inflammation. Results: In the experiment and control groups, the percentage of sites with BOP and PISA significantly decreased at the end of the experiment compared to the baseline. However, no significant differences were found between groups (p > 0.05). Conclusions: Administration of hydrogen-rich jelly for 14 days decreased gingival inflammation. However, no significant differences were identified compared to the control group. en-copyright= kn-copyright= en-aut-name=MaruyamaTakayuki en-aut-sei=Maruyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakayamaEiji en-aut-sei=Takayama en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokunoShinichi en-aut-sei=Tokuno en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Biochemistry, Asahi University School of Dentistry kn-affil= affil-num=3 en-affil=Graduate School of Health Innovation, Kanagawa University of Human Services kn-affil= affil-num=4 en-affil=Department of Oral Health, Takarazuka University of Medical and Health Care kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=periodontal disease kn-keyword=periodontal disease en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=hydrogen kn-keyword=hydrogen en-keyword=randomized controlled trial kn-keyword=randomized controlled trial END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=9 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=S-nitrosylation of laforin inhibits its phosphatase activity and is implicated in Lafora disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, the relation between S-nitrosylation by nitric oxide (NO), which is over?produced under pathological conditions and neurodegenerative diseases, includingAlzheimer’s and Parkinson’s diseases, has become a focus of attention. Although mostcases of Parkinson’s disease are known to be caused by mutations in the Parkin gene, arecent finding has indicated that S-nitrosylation of Parkin affects its enzymatic activityand leads to the Parkinsonian phenotype. Therefore, it is important to understand thefunction of S-nitrosylated proteins in the pathogenesis of neurodegenerative diseases.Lafora disease (LD, OMIM 254780) is a neurodegenerative disease characterized by theaccumulation of insoluble glucans called Lafora bodies (LBs). LD is caused by mutationsin genes that encode the glucan phosphatase, Laforin, or the E3 ubiquitin ligase, Malin.In this study, we hypothesized that LD may be caused by S-nitrosylation of Laforin,which is similar to the finding that Parkinson’s disease is caused by S-nitrosylation ofParkin. To test this hypothesis, we first determined whether Laforin was S-nitrosylatedusing a biotin switch assay, and compared the three main functions of unmodified andS-nitrosylated Laforin, namely glucan- and Malin-binding activity and phosphataseactivity. Furthermore, we examined whether the numbers of LBs were changed byNO in the cells expressing wild-type Laforin. Here, we report for the first time thatS-nitrosylation of Laforin inhibited its phosphatase activity and that LB formation wasincreased by an NO donor. Our results suggest a possible hypothesis for LD pathogenesis; that is, the decrease in phosphatase activity of Laforin by S-nitrosylation leads toincreased LB formation. Therefore, LD may be caused not only by mutations in theLaforin or Malin genes, but also by the S-nitrosylation of Laforin. en-copyright= kn-copyright= en-aut-name=ToyotaRikako en-aut-sei=Toyota en-aut-mei=Rikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HonjoYasuko en-aut-sei=Honjo en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ImajoRisa en-aut-sei=Imajo en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= en-keyword=S-Nitrosylation Of Laforin kn-keyword=S-Nitrosylation Of Laforin en-keyword=Post-Translational Modification kn-keyword=Post-Translational Modification en-keyword=Nitrosylation kn-keyword=Nitrosylation en-keyword=Phosphatase kn-keyword=Phosphatase en-keyword=Glucan-Binding kn-keyword=Glucan-Binding END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=252 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characteristics of oral mucositis in patients undergoing haploidentical stem cell transplantation with posttransplant cyclophosphamide: marked difference between busulfan and melphalan regimens en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose This study was performed to examine the effects of conditioning regimens on oral mucositis in haploidentical (haplo) donor hematopoietic stem cell transplantation (HSCT) with posttransplant cyclophosphamide (PTCy).
Methods Thirty consecutive patients (male, 23; female, 7; 18?68 years, median, 59 years) undergoing haplo-HSCT with PTCy using one of three conditioning regimens?reduced intensity conditioning (RIC)-melphalan (Mel); RIC-Busulfan (Bu); and myeloablative conditioning (MAC)-Bu?were enrolled in this study. Data on the WHO grade of oral mucositis (day???7 to?+?20) were collected retrospectively. The incidences of ulcerative and severe mucositis (Grade 2?4 and Grade 3?4, respectively) were compared between the three groups.
Results Ulcerative mucositis occurred in 0% (0/10) of patients in the RIC-Mel group, 57.1% (4/7) in the RIC-Bu group, and 100% (13/13) in the MAC-Bu group. The differences between the RIC-Mel and RIC-Bu groups and between the RIC-Bu and MAC-Bu groups were significant (all P? Conclusion The risk of oral mucositis in patients undergoing haplo-HSCT with PTCy is highest with the MAC-Bu conditioning regimen, followed by RIC-Bu, and lowest with RIC-Mel. en-copyright= kn-copyright= en-aut-name=OguraSaki en-aut-sei=Ogura en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiuraRumi en-aut-sei=Miura en-aut-mei=Rumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Dental Hygienist, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Hospital Dentistry, 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=Division of Dental Hygienist, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Division of Dental Hygienist, Okayama University Hospital kn-affil= en-keyword=Oral mucositis kn-keyword=Oral mucositis en-keyword=Hematopoietic cell transplantation kn-keyword=Hematopoietic cell transplantation en-keyword=Posttransplant cyclophosphamide kn-keyword=Posttransplant cyclophosphamide en-keyword=Busulfan kn-keyword=Busulfan en-keyword=Melphalan kn-keyword=Melphalan END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=3 article-no= start-page=32 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rapid development of naked malting barley germplasm through targeted mutagenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Covered barley (Hordeum vulgare) has historically been preferred for malting, as the husk in this plant protects the embryo during harvest and acts as a filter during brewing. Naked barley, which is typically used as food, has the potential to be used in brewing due to recent technical advances, but the grains contain higher levels of β-glucan and polyphenols, which are undesirable in brewing. Introducing the naked trait into brewing cultivars through crossing is time-consuming due to the need to eliminate these undesirable traits. In this study, we rapidly developed naked barley that is potentially suitable for malting by introducing targeted mutations into Nudum (NUD) using CRISPR/Cas9-mediated targeted mutagenesis. The doubled haploid line ‘DH120366’, which was used as the parental line, was derived from a cross between two covered malting barley cultivars. We generated CRISPR/Cas9-mediated targeted mutagenized barley harboring mutations in NUD via Agrobacterium tumefaciens-mediated transformation and confirmed the presence of mosaic mutations in one individual from among 16 T0 transformants. We sowed T1 grains exhibiting the naked trait and sequenced the NUD gene in these T1 seedlings, identifying two types of mutations. Shotgun high-throughput whole-genome sequencing confirmed the absence of the transgene in at least one nud mutant line following k-mer-based analysis. Cultivation in a closed growth chamber revealed no significant differences in agronomic traits between the nud mutants and the wild type. This study demonstrates the feasibility of rapidly developing naked barley with potential use for malting and brewing by targeting only NUD via targeted mutagenesis. en-copyright= kn-copyright= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakaiHiroaki en-aut-sei=Sakai en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamaokaMika en-aut-sei=Hamaoka en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MunemoriHiromi en-aut-sei=Munemori en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbeFumitaka en-aut-sei=Abe en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MeintsBrigid en-aut-sei=Meints en-aut-mei=Brigid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HayesPatrick M. en-aut-sei=Hayes en-aut-mei=Patrick M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Research Center for Advanced Analysis, National Agriculture and Food Research Organization kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Institute of Crop Science, National Agriculture and Food Research Organization kn-affil= affil-num=6 en-affil=Department Crop and Soil Science, Oregon State University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=8 en-affil=Department Crop and Soil Science, Oregon State University kn-affil= en-keyword=Hordeum vulgare kn-keyword=Hordeum vulgare en-keyword=Covered (hulled) kn-keyword=Covered (hulled) en-keyword=Naked (hull-less) kn-keyword=Naked (hull-less) en-keyword=Genome editing kn-keyword=Genome editing en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=Transformation amenability kn-keyword=Transformation amenability END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=e70096 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=Endoscopic ultrasonography-guided removal of a stent that had migrated into the pancreas post-pancreaticojejunostomy: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 64-year-old woman had undergone subtotal stomach-preserving pancreaticoduodenectomy for locally advanced pancreatic head cancer. She had an uneventful postoperative course with no recurrence. However, approximately 18 months after surgery, she presented with recurrent abdominal pain. Although contrast-enhanced computed tomography abdominal radiographs showed internal stent migration to the residual pancreas, dilatation of the tail side of the pancreatic duct was observed. The impaired internal stent was considered to be the cause of the abdominal pain. An attempt to remove the stent via balloon-assisted endoscopy was unsuccessful as the pancreaticojejunostomy site could not be reached. Consequently, endoscopic ultrasonography-guided pancreatic duct drainage was performed, and a plastic stent was placed through the jejunal site to the stomach. Two months later, the endosonographically/endoscopic ultrasonography-guided created route was dilated, and an endoscopic introducer was inserted into the pancreatic duct. Biopsy forceps were advanced through the sheath, allowing the successful removal of the stent by direct grasping. The symptoms of the patient improved, and she was discharged without complications. en-copyright= kn-copyright= en-aut-name=KajitaniSatoshi en-aut-sei=Kajitani en-aut-mei=Satoshi 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=OkiKentaro en-aut-sei=Oki en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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 andHepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology andHepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology andHepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology andHepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology andHepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology andHepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology andHepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology andHepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology andHepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology andHepatology, Okayama University Hospital kn-affil= en-keyword=endoscopic introducer kn-keyword=endoscopic introducer en-keyword=endoscopic ultrasonography-guided pancreatic duct drainage kn-keyword=endoscopic ultrasonography-guided pancreatic duct drainage en-keyword=endosonographically/EUS-guided created route kn-keyword=endosonographically/EUS-guided created route en-keyword=EUS-guided interventions kn-keyword=EUS-guided interventions en-keyword=internal stent kn-keyword=internal stent END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=1 article-no= start-page=35 end-page=40 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=Evaluation of CT Findings in Squamous and Non-Squamous Cell Carcinomas of the Maxillary Sinus en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of the present study was to compare CT images between squamous cell carcinoma (SCC) and non-SCC found in the maxillary sinus, and to identify features that could be used to differentiate between SCC and non-SCC. Patients who visited the Faculty of Dentistry, Okayama University Hospital, between April 2007 and March 2023, underwent head and neck CT, and had tumors extending into the maxillary sinus that were diagnosed histopathologically as malignancy, were enrolled. The main seat of the mass, bony changes in the maxillary sinus wall, and extension into the surrounding area were assessed. These imaging features were evaluated according to SCC or non-SCC, and the characteristics of the two classes were assessed. Comparisons between the two groups were made using the Fisher exact probability test. There were 11 cases each of SCC and non-SCC. In 11 SCC and 7 non-SCC cases, the main seat of the mass occupied the entire maxillary sinus. The frequency of mass occupying the whole sinus was significantly higher in SCC than in non-SCC (p<0.05). Bone-thickening type disease was found only in squamous cell carcinoma 4/11 (36.4%), with there being a significant difference between SCC and non-SCC (p<0.05). Occupancy of the entire maxillary sinus by the mass and bone thickening on CT images were useful for differentiating between SCC and non-SCC arising in the maxillary sinus. en-copyright= kn-copyright= en-aut-name=AsaumiYuka en-aut-sei=Asaumi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=E. Al-HammadWlla en-aut-sei=E. Al-Hammad en-aut-mei=Wlla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=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=YanagiYoshinobu en-aut-sei=Yanagi en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital 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 Dental Informatics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Maxillary sinus kn-keyword=Maxillary sinus en-keyword=Squamous cell carcinoma kn-keyword=Squamous cell carcinoma en-keyword=Non-squamous cell carcinoma kn-keyword=Non-squamous cell carcinoma en-keyword=CT kn-keyword=CT END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue= article-no= start-page=106690 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=EGF-induced P-gp expression in tumor vasculature contributes to therapeutic resistance to doxorubicin-PEG-liposomes in mice bearing doxorubicin-resistant B16-BL6 tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously indicated that doxorubicin (DOX)-loaded polyethylene glycol (PEG)-modified liposomes (DOX-PEG-liposomes) were therapeutically effective in mice bearing DOX-resistant colon-26 (C26/DOX) tumors, and the efficacy was comparable in mice bearing DOX-sensitive C26 tumors. However, in the current study, DOX-PEG-liposomes exerted no therapeutic activity in DOX-resistant B16-BL6 melanoma (B16/DOX)-bearing mice, although they significantly suppressed DOX-sensitive B16 tumor growth in mice. Although we previously reported that the anti-tumor effects in C26/DOX-bearing mice were derived from the cytotoxic effects of DOX on vascular endothelial cells (VECs) in tumors, the B16/DOX tumor vasculature was not substantially damaged after administration of DOX-PEG-liposomes. In B16/DOX tumors, P-gp expression was significantly induced in the VECs, but not in the C26/DOX tumors, indicating that the high expression of P-gp in the tumor vasculature would be responsible for the lack of therapeutic effect of DOX-PEG-liposomes in B16/DOX-bearing mice. Epidermal growth factor (EGF), a possible induction factor for P-gp expression, was highly expressed in B16/DOX cells and tumor tissues, and significantly induced P-gp expression in human umbilical vein endothelial cells (HUVEC). The EGF receptor (EGFR) was also highly expressed in B16/DOX tumor VECs, suggesting that the activation of EGF/EGFR signaling may induce P-gp expression in VECs in B16/DOX tumors. en-copyright= kn-copyright= en-aut-name=MaruyamaMasato en-aut-sei=Maruyama en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaTomoki en-aut-sei=Ueda en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IenakaYusuke en-aut-sei=Ienaka en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TojoHaruka en-aut-sei=Tojo en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HyodoKenji en-aut-sei=Hyodo en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OgawaraKen-ichi en-aut-sei=Ogawara en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigakiKazutaka en-aut-sei=Higaki en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Eisai Co., Ltd. kn-affil= affil-num=6 en-affil=Laboratory of Pharmaceutics, Kobe Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Drug resistance kn-keyword=Drug resistance en-keyword=P-glycoprotein kn-keyword=P-glycoprotein en-keyword=Liposome kn-keyword=Liposome en-keyword=Tumor vascular endothelial cells kn-keyword=Tumor vascular endothelial cells en-keyword=Melanoma kn-keyword=Melanoma END start-ver=1.4 cd-journal=joma no-vol=209 cd-vols= no-issue= article-no= start-page=114663 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Repeated sequential administration of pegylated emulsion of SU5416 and liposomal paclitaxel enhances anti-tumor effect in 4T1 breast cancer-bearing mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=To improve vascular normalization strategy for intractable triple-negative breast cancer 4T1, we examined the anti-tumor effects of repeated sequential administration of polyethylene glycol (PEG)-modified emulsion of SU5416 (PE-SU5416), a vascular endothelial growth factor (VEGF) receptor-2 kinase inhibitor, and PEG-modified liposomal paclitaxel (PL-PTX) in mice bearing 4T1 cells. Three sequential administrations (Seq×3) of PE-SU5416 and PL-PTX exhibited significantly higher anti-tumor activity than a single sequential administration (Seq×1). The tumor vasculatures were structurally normalized until after two PE-SU5416 (PE-SU5416×2) or sequential (Seq×2) administrations, while the improvement in vascular function, such as oxygen supply, blood flow, and PEG-liposomal distribution, was evident until after three administrations of PE-SU5416 (PE-SU5416×3) and Seq×3. Although some discrepancies between the structural and functional improvement in tumor vasculatures were observed after PE-SU5416×3 and Seq×3, cancer-associated fibroblasts (CAFs) and collagen levels were significantly reduced after PE-SU5416×2, PE-SU5416×3, Seq×2, and Seq×3, suggesting that a possible decrease in interstitial fluid pressure due to the reduction in CAFs and collagen would have compensated for vascular function. Furthermore, PE-SU5416×2, PE-SU5416×3, Seq×2, and Seq×3 significantly decreased tumor growth factor-β (TGF-β), an activator of CAFs, in tumor tissues, suggesting that the reduction in TGF-β levels by PE-SU5416 suppresses CAF activation. en-copyright= kn-copyright= en-aut-name=MaruyamaMasato en-aut-sei=Maruyama en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToriiReiya en-aut-sei=Torii en-aut-mei=Reiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuiHazuki en-aut-sei=Matsui en-aut-mei=Hazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayashiHiroki en-aut-sei=Hayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgawaraKen-ichi en-aut-sei=Ogawara en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigakiKazutaka en-aut-sei=Higaki en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Laboratory of Pharmaceutics, Kobe Pharmaceutical University kn-affil= affil-num=6 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Drug delivery kn-keyword=Drug delivery en-keyword=Vascular normalization kn-keyword=Vascular normalization en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Liposome kn-keyword=Liposome en-keyword=Cancer-associated fibroblast kn-keyword=Cancer-associated fibroblast 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=20250224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD en-subtitle= kn-subtitle= en-abstract= kn-abstract=Therapies that effectively suppress graft-versus-host disease (GVHD) without compromising graft-versus-leukemia/lymphoma (GVL) effects is important in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic malignancies. Geranylgeranylacetone (GGA) is a main component of teprenone, a gastric mucosal protectant commonly used in clinical practice. In preclinical models, GGA suppresses proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), which are associated with GVHD as well as induces thioredoxin-1 (Trx-1), which suppresses GVHD while maintaining GVL effects. Here, we investigated whether the addition of teprenone to standard GVHD prophylaxis could reduce the cumulative incidence of severe acute GVHD (aGVHD) without attenuating GVL effects. This open-label, randomized clinical trial enrolled 40 patients (21 control and 19 teprenone group) who received allo-HSCT between May 2022 and February 2023 in our institution. Patients in the teprenone group received 50 mg of teprenone orally thrice daily for 21 days from the initiation of the conditioning regimen. The cumulative incidence of severe aGVHD by day 100 after allo-HSCT was not significantly different in the two groups (27.9 vs. 16.1%, p?=?0.25). The exploratory studies revealed no obvious changes in Trx-1 levels, but the alternations from baseline in IL-1β and TNF-α levels at day 28 after allo-HSCT tended to be lower in the teprenone group. In conclusion, we could not demonstrate that teprenone significantly prevented the development of severe aGVHD. Discrepancy with preclinical model suggests that appropriate dose of teprenone may be necessary to induce the expression of antioxidant enzymes that suppress severe aGVHD. Clinical Trial Registration number:jRCTs 061210072. 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=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 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=11 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=12 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 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 Pediatric Acute Diseases, Okayama University Academic Field of Medicine Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital 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, 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= en-keyword=Allogeneic hematopoietic stem cell transplantation kn-keyword=Allogeneic hematopoietic stem cell transplantation en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Teprenone kn-keyword=Teprenone en-keyword=Oxidative stress kn-keyword=Oxidative stress en-keyword=Interleukin-33 kn-keyword=Interleukin-33 END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=2 article-no= start-page=61 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study of Podoplanin-Deficient Mouse Bone with Mechanical Stress en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: We investigated morphological differences in osteocyte processes between aged mice and our original podoplanin-conditional knockout (cKO) mice in which the floxed exon 3 of podoplanin was deleted by Dmp-1-driven Cre (Dmp1-Cre;PdpnΔ/Δ). Methods: SEM observation on osteocyte cell process, histochemistry for bone remodeling with mechanostress, and RT-PCR for RANKL and M-CSF in podoplanin cKO mouse bone with mechanostress was investigated. Results: SEM observations showed fewer and thinner osteocyte processes in femurs from 23-week-old Dmp1-Cre;PdpnΔ/Δ mice than from 23-week-old wild-type mice, while the numbers of osteocyte processes in femurs and calvarias were similar in 23-week-old Dmp1-Cre;PdpnΔ/Δ mice and 48-week-old wild-type mice. Furthermore, cell process numbers in femurs and calvarias were significantly smaller in 23-week-old Dmp1-Cre;PdpnΔ/Δ mice than in 48-week-old wild-type mice. In the test for differences in alveolar bone resorption under mechanical stress between Dmp1-Cre;PdpnΔ/Δ and wild-type mice, the area of TRAP-positive resorption pits was larger in wild-type mice than in Dmp1-Cre;PdpnΔ/Δ mice. In a quantitative tissue PCR analysis, the mRNA expression levels of RANKL and M-CSF in alveolar bone under mechanical stress were significantly lower in Dmp1-Cre;PdpnΔ/Δ mice than in wild-type mice. These results suggest that a reduction in cell process formation in osteocytes with podoplanin cKO affected the absorption of alveolar bone under mechanical stress in Dmp1-Cre;PdpnΔ/Δ mice. Conclusions: In podoplanin-deficient bone, the deformation of osteocyte processes by mechanical stimuli is not recognized as a stress due to the lower number of cell processes with podoplanin deficiency; therefore, the production of osteoclast migration/differentiation factors by activated osteocytes is not fully induced and macrophage migration to alveolar bone with mechanical stress appeared to be suppressed. These results indicate that podoplanin-dependent osteocyte process formation indirectly plays a key role in sensing mechanical stress in bone. en-copyright= kn-copyright= en-aut-name=KanaiTakenori en-aut-sei=Kanai en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OsawaKyoko en-aut-sei=Osawa en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KajiwaraKoichiro en-aut-sei=Kajiwara en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoYoshiaki en-aut-sei=Sato en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SawaYoshihiko en-aut-sei=Sawa en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=3 en-affil=Department of Oral Growth & Development, Hokkaido University kn-affil= affil-num=4 en-affil=Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=5 en-affil=Department of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=podoplanin kn-keyword=podoplanin en-keyword=cKO kn-keyword=cKO en-keyword=osteocyte kn-keyword=osteocyte en-keyword=bone kn-keyword=bone en-keyword=remodeling kn-keyword=remodeling END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=4 article-no= start-page=1055 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Natural Course and Long-Term Outcomes of Gastric Subepithelial Lesions: A Systematic Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Gastric subepithelial lesions (SELs) are often incidentally detected during endoscopic examinations, with most patients being asymptomatic and lesions measuring <20 mm. Despite their generally indolent nature, certain SELs, such as gastrointestinal stromal tumors, require resection. Current guidelines recommend periodic surveillance; however, the natural course and long-term outcomes of gastric SELs have not been sufficiently investigated. This systematic review aimed to synthesize evidence on the progression, growth rate, and risk factors associated with gastric SELs to inform clinical management strategies. Methods: A comprehensive search of PubMed was conducted for peer-reviewed studies published between January 2000 and November 2024. Eligible studies included original studies on the follow-up and progression of gastric SELs. Non-English articles, reviews, case reports, and unrelated topics were excluded. In total, 277 articles were screened, with 15 additional articles identified through manual screening. Ultimately, 41 articles were included in the analysis. The study protocol is registered in PROSPERO (CRD42024614865). Results: Large-scale studies reported low growth rates of 2.0-8.5% over 2.0-5.0 years, while smaller studies reported a broader range of growth rates of 5.4-28.4%. The factors contributing to these discrepancies include patient selection, follow-up duration, and growth criteria. Risk factors for lesion size increase include larger initial lesion size, irregular margins, heterogeneous echo patterns, and certain tumor locations. Conclusions: These findings underscore the need for individualized management strategies based on lesion size, imaging characteristics, and risk factors. The close monitoring of high-risk lesions is crucial for timely intervention. Standardized growth criteria and optimized follow-up protocols are essential for improving clinical decision making and patient outcomes. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= 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 Internal Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=3 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=gastric lesions kn-keyword=gastric lesions en-keyword=gastrointestinal stromal tumor kn-keyword=gastrointestinal stromal tumor en-keyword=subepithelial lesion kn-keyword=subepithelial lesion en-keyword=submucosal tumor kn-keyword=submucosal tumor END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=e70077 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case of invasive pulmonary aspergillosis associated with clozapine-induced agranulocytosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Clozapine-induced agranulocytosis (CLIA) is a rare but serious complication. Fever associated with CLIA is typically treated with broad-spectrum antimicrobials, but empiric antifungal therapy is rarely used. While bacterial and viral infections have been reported in CLIA cases, no cases of fungal infections complicated by CLIA have been documented. We report the first case of CLIA complicated by invasive pulmonary aspergillosis (IPA) in a patient with schizophrenia. The diagnosis of IPA was made using serum beta-D-glucan, Aspergillus galactomannan antigen tests, and chest computed tomography (CT).
Case presentation: We present a case of a 51-year-old man with schizophrenia who developed CLIA complicated by IPA. The patient, diagnosed with treatment-resistant schizophrenia, was started on clozapine, but 9 months later he presented with fever, cough, leukopenia, and neutropenia. Clozapine was discontinued, and empirical treatments with cefepime and filgrastim were initiated. Serum beta-D-glucan and Aspergillus galactomannan antigen tests were positive, and chest CT showed well-circumscribed nodules, leading to a probable diagnosis of IPA. Antifungal therapy was switched from micafungin to voriconazole according to guidelines. His neutropenia and fever improved, and he was re-transferred to a psychiatric hospital.
Conclusion: CLIA can be complicated by fungal infections. When patients with CLIA present with fever, fungal infections, including IPA, should be considered in the differential diagnosis. Serological tests, including beta-D-glucan and Aspergillus galactomannan, are useful for the diagnosis of IPA as well as the appropriate use of antifungal agents in patients with CLIA. en-copyright= kn-copyright= en-aut-name=YokodeAkiyoshi en-aut-sei=Yokode en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoRyota en-aut-sei=Sato en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MishimaMomoko en-aut-sei=Mishima en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YadaYuji en-aut-sei=Yada en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, 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 Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=7 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=8 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=9 en-affil=Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=10 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=clozapine-induced agranulocytosis kn-keyword=clozapine-induced agranulocytosis en-keyword=fungal infections kn-keyword=fungal infections en-keyword=invasive pulmonary aspergillosis kn-keyword=invasive pulmonary aspergillosis en-keyword=schizophrenia kn-keyword=schizophrenia END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=4 article-no= start-page=1391 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Course of General Fatigue in Patients with Post-COVID-19 Conditions Who Were Prescribed Hochuekkito: A Single-Center Exploratory Pilot Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: After the start of the COVID-19 pandemic, general fatigue in patients with long COVID and post-COVID-19 conditions (PCC) became a medical issue. Although there is a lack of evidence-based treatments, Kampo medicine (traditional Japanese medicine) has gained attention in Japan. At an outpatient clinic in Japan specializing in long COVID, 24% of all prescriptions were Kampo medicines, and 72% of Kampo medicine prescriptions were hochuekkito. However, there has been no prospective, quantitative study on the course of fatigue in patients with long COVID and PCC who were prescribed hochuekkito. The aim of this study was to clarify the course of fatigue in those patients. Methods: This study included patients aged 18 years or older with general fatigue who visited the long COVID specialized outpatient clinic at Okayama University Hospital and consented to participate after being prescribed hochuekkito. We reviewed the backgrounds of the patients, and we evaluated the patients' fatigue assessment scale in person or online. Results: Twenty patients were enrolled in this study from September to December in 2023. The average age of the patients was 42.9 years (SD: 15.8 years) and 12 patients (60%) were female. After hochuekkito administration, the fatigue assessment scale score decreased from 35.9 (SD: 5.9) at the initial visit to 31.2 (SD: 9.4) after 8 weeks, indicating a trend for improvement in fatigue (difference: 4.7; 95% CI: 0.5-8.9). Conclusions: A trend for improvement in fatigue was observed in patients with long COVID and PCC who were prescribed hochuekkito, indicating a potential benefit of hochuekkito for general fatigue in such patients. General fatigue in patients with long COVID or PCC can be classified as post-infectious fatigue syndrome and is considered a condition of qi deficiency in Kampo medicine, for which hochuekkito is appropriately indicated. en-copyright= kn-copyright= en-aut-name=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukiNobuyoshi en-aut-sei=Matsuki en-aut-mei=Nobuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoYoko en-aut-sei=Sakamoto en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UedaKeigo en-aut-sei=Ueda en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsudaYui en-aut-sei=Matsuda en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakuradaYasue en-aut-sei=Sakurada en-aut-mei=Yasue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HondaHiroyuki en-aut-sei=Honda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HasegawaToru en-aut-sei=Hasegawa en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakaseRyosuke en-aut-sei=Takase en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OmuraDaisuke en-aut-sei=Omura en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= affil-num=1 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=fatigue assessment scale (FAS) kn-keyword=fatigue assessment scale (FAS) en-keyword= general fatigue kn-keyword= general fatigue en-keyword= hochuekkito kn-keyword= hochuekkito en-keyword= kampo medicine kn-keyword= kampo medicine en-keyword= long COVID kn-keyword= long COVID en-keyword= post-COVID-19 condition kn-keyword= post-COVID-19 condition END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=2 article-no= start-page=267 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Abnormal Expression of Tubular SGLT2 and GULT2 in Diabetes Model Mice with Malocclusion-Induced Hyperglycemia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: A relationship between malocclusion and the promotion of diabetes has been suggested. In hyperglycemia, the expression of sodium-glucose cotransporter 2 (SGLT2) and the facilitative glucose transporter 2 (GLUT2) is upregulated in proximal tubular cells, leading to an increase in renal glucose reabsorption. The present study aimed to investigate whether malocclusion contributes to diabetic exacerbation. Methods: Streptozotocin (STZ)-induced diabetic mice with malocclusion due to cutting molars were investigated based on increased blood glucose levels. PCR and immunohistochemical analyses were performed on diabetic mice kidneys to investigate the expression of SGLT2 and GLUT2. Results: Animal experiments were performed using 32 mice for 21 days. The time to reach a diabetic condition in STZ-administered mice was shorter with malocclusion than without malocclusion. The increase and mean blood glucose levels in STZ-administered mice were steeper and higher with malocclusion than without malocclusion. Urea albumin, BUN, and CRE levels were higher in diabetic mice with malocclusion than in diabetic mice without. Immunoreaction with anti-SGLT2 and anti-GLUT2 in the renal tissue of STZ-administered mice was stronger with malocclusion than without malocclusion. The amounts of SGLT2 and GLUT2 mRNA in the renal tissue in STZ-administered mice were higher with malocclusion than without malocclusion. The amounts of TNF-a and IL-6 mRNA in the large intestinal tissue in STZ-administered mice were higher with malocclusion than without malocclusion. Conclusions: Our results indicate that malocclusion accelerates the tubular expression of SGLT2 and GLUT2 under hyperglycemia. Malocclusion may be a diabetes-exacerbating factor with increased poor glycemic control due to shortened occlusion time resulting from swallowing food without chewing. en-copyright= kn-copyright= en-aut-name=KajiwaraKoichiro en-aut-sei=Kajiwara en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TamaokiSachio en-aut-sei=Tamaoki en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SawaYoshihiko en-aut-sei=Sawa en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Oral Growth & Development, Fukuoka Dental College kn-affil= affil-num=2 en-affil=Department of Oral Growth & Development, Fukuoka Dental College kn-affil= affil-num=3 en-affil=Department of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=malocclusion kn-keyword=malocclusion en-keyword= hyperglycemia kn-keyword= hyperglycemia en-keyword= SGLT2 kn-keyword= SGLT2 en-keyword= GLUT2 kn-keyword= GLUT2 END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=235 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distinct Infection Mechanisms of Rhizoctonia solani AG-1 IA and AG-4 HG-I+II in Brachypodium distachyon and Barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rhizoctonia solani is a basidiomycete phytopathogenic fungus that causes rapid necrosis in a wide range of crop species, leading to substantial agricultural losses worldwide. The species complex is divided into 13 anastomosis groups (AGs) based on hyphal fusion compatibility and further subdivided by culture morphology. While R. solani classifications were shown to be independent of host specificity, it remains unclear whether different R. solani isolates share similar virulence mechanisms. Here, we investigated the infectivity of Japanese R. solani isolates on Brachypodium distachyon and barley. Two isolates, AG-1 IA (from rice) and AG-4 HG-I+II (from cauliflower), infected leaves of both plants, but only AG-4 HG-I+II infected roots. B. distachyon accessions Bd3-1 and Gaz-4 and barley cultivar 'Morex' exhibited enhanced resistance to both isolates compared to B. distachyon Bd21 and barley cultivars 'Haruna Nijo' and 'Golden Promise'. During AG-1 IA infection, but not AG-4 HG-I+II infection, resistant Bd3-1 and Morex induced genes for salicylic acid (SA) and N-hydroxypipecolic acid (NHP) biosynthesis. Pretreatment with SA or NHP conferred resistance to AG-1 IA, but not AG-4 HG-I+II, in susceptible B. distachyon Bd21 and barley Haruna Nijo. On the leaves of susceptible Bd21 and Haruna Nijo, AG-1 IA developed extensive mycelial networks with numerous infection cushions, which are specialized infection structures well-characterized in rice sheath blight. In contrast, AG-4 HG-I+II formed dispersed mycelial masses associated with underlying necrosis. We propose that the R. solani species complex encompasses at least two distinct infection strategies: AG-1 IA exhibits a hemibiotrophic lifestyle, while AG-4 HG-I+II follows a predominantly necrotrophic strategy. en-copyright= kn-copyright= en-aut-name=MahadevanNiranjan en-aut-sei=Mahadevan en-aut-mei=Niranjan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FernandaRozi en-aut-sei=Fernanda en-aut-mei=Rozi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KouzaiYusuke en-aut-sei=Kouzai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KohnoNatsuka en-aut-sei=Kohno en-aut-mei=Natsuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaoReiko en-aut-sei=Nagao en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NyeinKhin Thida en-aut-sei=Nyein en-aut-mei=Khin Thida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeMegumi en-aut-sei=Watanabe en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakataNanami en-aut-sei=Sakata en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MochidaKeiichi en-aut-sei=Mochida en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NoutoshiYoshiteru en-aut-sei=Noutoshi en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Crop Stress Management Group, Division of Plant Molecular Regulation Research, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO) kn-affil= affil-num=4 en-affil=Faculty of Agriculture, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Agriculture, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=12 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=13 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=14 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Rhizoctonia solani species complex kn-keyword=Rhizoctonia solani species complex en-keyword=virulence mechanism kn-keyword=virulence mechanism en-keyword=infection behavior kn-keyword=infection behavior en-keyword=salicylic acid kn-keyword=salicylic acid en-keyword=N-hydroxypipecolic acid kn-keyword=N-hydroxypipecolic acid END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=2 article-no= start-page=101 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiographic and Clinical Assessment of Unidirectional Porous Beta-Tricalcium Phosphate to Treat Benign Bone Tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=The purpose of this study was to evaluate radiographic changes, clinical outcomes, and complications following unidirectional porous beta-tricalcium phosphate (UDPTCP) implantation for the treatment of benign bone tumors. We retrospectively analyzed 46 patients who underwent intralesional resection. The patients were divided into two cohorts: Cohort 1 (n = 32), which included all bones except the phalanges and metacarpal/tarsal bones, and Cohort 2 (n = 14), which included the phalanges and metacarpal/tarsal bones. Radiographic changes were assessed at each reading based on resorption of the implanted UDPTCP and bone trabeculation through the defect. UDPTCP resorption and bone trabeculation were observed on radiographs within 3 months of surgery in all patients. Bone remodeling in the cavity progressed steadily for up to 3 years postoperatively. In Cohort 1, resorption and trabeculation progressed significantly in young patients, and trabeculation developed significantly in small lesions. The rates of resorption and trabeculation at 3 months postoperatively correlated statistically with their increased rates at one year. There was no statistical difference in resorption and trabeculation rates between Cohort 1 and Cohort 2. There were no cases of postoperative deep infections or allergic reactions related to the implant. UDPTCP is a useful bone-filling substitute for the treatment of benign bone tumors and has a low complication rate. en-copyright= kn-copyright= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki 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=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurozumiTakanao en-aut-sei=Kurozumi en-aut-mei=Takanao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AndoTeruhiko en-aut-sei=Ando en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=unidirectional porous beta-tricalcium phosphate kn-keyword=unidirectional porous beta-tricalcium phosphate en-keyword= bone tumor kn-keyword= bone tumor en-keyword= bone graft kn-keyword= bone graft en-keyword= radiography kn-keyword= radiography en-keyword= bone remodeling kn-keyword= bone remodeling END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e202403213 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250218 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Antifouling Activity of Xylemin, Its Structural Analogs, and Related Polyamines en-subtitle= kn-subtitle= en-abstract= kn-abstract=Biofouling, which is the accumulation of organisms on undersea structures, poses significant global, social, and economic issues. Although organotin compounds were effective antifoulants since the 1960s, they were banned in 2008 due to their toxicity to marine life. Although tin-free alternatives have been developed, they also raise environmental concerns. This underscores the need for effective, nontoxic antifouling agents. We previously synthesized N-(4-aminobutyl)propylamine (xylemin) and its structural analogs. In this study, we assayed the antifouling activity and toxicity of xylemin, its structural analogs, and related polyamines toward cypris larvae of the barnacle Amphibalanus amphitrite. Xylemin and its Boc-protected analog exhibited antifouling activities with 50% effective concentrations (EC50) of 4.25 and 6.11 ?g/mL, respectively. Four xylemin analogs did not show a settlement-inhibitory effect at a concentration of 50 ?g/mL. Putrescine, spermidine, spermine, and thermospermine, which are xylemin-related polyamines, did not display antifoulant effects (EC50 > 50 ?g/mL). All evaluated compounds were nontoxic at a concentration of 50 ?g/mL. These findings indicate that the size and structure of the N-alkyl group are essential for the antifouling activity of xylemin. Therefore, xylemin and its analogs hold promise as nontoxic, eco-friendly antifouling agents, offering a sustainable solution to biofouling in marine environments. en-copyright= kn-copyright= en-aut-name=TakamuraHiroyoshi en-aut-sei=Takamura en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YorisueTakefumi en-aut-sei=Yorisue en-aut-mei=Takefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Institute of Natural and Environmental Sciences, University of Hyogo kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Amines kn-keyword=Amines en-keyword=Antifouling activity kn-keyword=Antifouling activity en-keyword=Barnacle kn-keyword=Barnacle en-keyword=Structure?activity relationships kn-keyword=Structure?activity relationships en-keyword=Xylemin kn-keyword=Xylemin END start-ver=1.4 cd-journal=joma no-vol=197 cd-vols= no-issue= article-no= start-page=115301 end-page= 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=Fraglide-1 from traditional Chinese aromatic vinegar: A natural AhR antagonist for atopic dermatitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Traditional Chinese Zhenjiang aromatic vinegar (Kozu) contains Fraglide-1 (FG1), a bioactive lactone with demonstrated peroxisome proliferator-activated receptor gamma (PPARγ) agonist and antioxidant activities. This study explored FG1's novel ability to antagonize the aryl hydrocarbon receptor (AhR) signaling pathway, which regulates artemin expression and contributes to itching and inflammation in atopic dermatitis. Through molecular docking simulations and cell-based assays in human keratinocytes, we demonstrated FG1's potent antagonistic activity against AhR signaling. FG1 effectively suppressed FICZ-induced inflammatory responses, including artemin expression, with potency (half maximal inhibitory concentration, IC50 = 5.1 μM) comparable to the synthetic antagonist StemRegenin 1 (SR1) while demonstrating a superior safety profile (median lethal concentration, LC50 > 100 μM vs. 27.5 μM for SR1). These findings expand our understanding of bioactive compounds from traditional fermented foods and their regulatory effects on AhR signaling, providing a foundation for future studies on FG1's role in modulating skin inflammation. en-copyright= kn-copyright= en-aut-name=KatoKosuke en-aut-sei=Kato en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkamatsuMiki en-aut-sei=Akamatsu en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KakimaruSaya en-aut-sei=Kakimaru en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KoreishiMayuko en-aut-sei=Koreishi en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakagiMasahiro en-aut-sei=Takagi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyashitaMasahiro en-aut-sei=Miyashita en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujinoYoshio en-aut-sei=Tsujino en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=School of Materials Science, Japan Advanced Institute of Science and Technology kn-affil= affil-num=6 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Science, Technology and Innovation, Kobe University kn-affil= en-keyword=AhR kn-keyword=AhR en-keyword=Xenobiotic responsive element kn-keyword=Xenobiotic responsive element en-keyword=StemRegenin 1 kn-keyword=StemRegenin 1 en-keyword=ARNT kn-keyword=ARNT en-keyword=Atopic dermatitis kn-keyword=Atopic dermatitis en-keyword=Artemin kn-keyword=Artemin END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue=10 article-no= start-page=1241 end-page=1252 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome is a heterogeneous entity manifesting with a constellation of symptoms described above that can occur in the context of idiopathic multicentric Castleman disease (iMCD) as well as infectious diseases, malignancies, and rheumatologic disorders. So, iMCD-TAFRO is an aggressive subtype of iMCD with TAFRO syndrome and often hyper-vascularized lymph nodes. Since we proposed diagnostic criteria of iMCD-TAFRO in 2016, we have accumulated new insights on the disorder and additional cases have been reported worldwide. In this systematic review and cohort analysis, we established and validated a definition for iMCD-TAFRO. First, we searched PubMed and Japan Medical Abstracts Society databases using the keyword “TAFRO” to extract cases. Patients with possible systemic autoimmune diseases and hematologic malignancies were excluded. Our search identified 54 cases from 50 articles. We classified cases into three categories: (1) iMCD-TAFRO (TAFRO syndrome with lymph node histopathology consistent with iMCD), (2) possible iMCD-TAFRO (TAFRO syndrome with no lymph node biopsy performed and no other co-morbidities), and (3) TAFRO without iMCD or other co-morbidities (TAFRO syndrome with lymph node histopathology not consistent with iMCD or other comorbidities). Based on the findings, we propose an international definition requiring four clinical criteria (thrombocytopenia, anasarca, fever/hyperinflammatory status, organomegaly), renal dysfunction or characteristic bone marrow findings, and lymph node features consistent with iMCD. The definition was validated with an external cohort (the ACCELERATE Natural History Registry). The present international definition will facilitate a more precise and comprehensive approach to the diagnosis of iMCD-TAFRO. en-copyright= kn-copyright= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PiersonSheila K. en-aut-sei=Pierson en-aut-mei=Sheila K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwakiNoriko en-aut-sei=Iwaki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KawanoMitsuhiro en-aut-sei=Kawano en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraNaoya en-aut-sei=Nakamura en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IzutsuKoji en-aut-sei=Izutsu en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiKengo en-aut-sei=Takeuchi en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 ORCID= en-aut-name=YoshizakiKazuyuki en-aut-sei=Yoshizaki en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OksenhendlerEric en-aut-sei=Oksenhendler en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=van RheeFrits en-aut-sei=van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=3 en-affil=Center for Cytokine Storm Treatment & Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=4 en-affil=Hematology/Respiratory Medicine, Kanazawa University Graduate School of Medical Science kn-affil= affil-num=5 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Rheumatology, Kanazawa University Graduate School of Medical Science kn-affil= affil-num=7 en-affil=Department of Pathology, Tokai University School of Medicine kn-affil= affil-num=8 en-affil=Department of Hematology, National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Organic Fine Chemicals, Institute of Scientific and Industrial Research, Osaka University kn-affil= affil-num=14 en-affil=Department of Clinical Immunology, H?pital Saint-Louis kn-affil= affil-num=15 en-affil=Myeloma Center, University of Arkansas for Medical Sciences kn-affil= affil-num=16 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=53 cd-vols= no-issue=1 article-no= start-page=3 end-page=10 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250131 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigation of SNPs associated with reproductive and body growth traits in Vietnamese and Nepalese native buffaloes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Water buffaloes are essential to the rural economies of many developing countries, including Vietnam and Nepal, but native buffalo populations in these countries face challenges such as low productivity due to fertility and body growth issues. This study analyzed 34 SNPs in 18 genes associated with reproductive and body growth traits reported in cattle and buffalo in Vietnamese and Nepalese native buffaloes. Results showed no polymorphism at bovine SNPs in either buffalo. Further analysis with SNPs previously reported only in popular buffalo breeds, such as Murrah, found that Vietnamese buffalo were monomorphic at all sites, which may reflect reduced genetic diversity due to population decline. In contrast, Nepalese buffalo, consisting of two native breeds, showed polymorphism in 11 SNPs in 7 genes, with 10 of these matching those found in the Murrah buffalo analyzed here. These findings suggest that these SNPs may be applicable for genetic improvement in Nepalese native buffalo. This study provides valuable insights for future conservation and breeding programs aimed at enhancing reproductive and body growth performance of native buffalo in Vietnam and Nepal. en-copyright= kn-copyright= en-aut-name=Thuy ThanhNguyen en-aut-sei=Thuy Thanh en-aut-mei=Nguyen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=Manoj KumarShah en-aut-sei=Manoj Kumar en-aut-mei=Shah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Thu Nu AnhLe en-aut-sei=Thu Nu Anh en-aut-mei=Le kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Van HuuNguyen en-aut-sei=Van Huu en-aut-mei=Nguyen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UshijimaKoichiro en-aut-sei=Ushijima en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaeMayuko en-aut-sei=Nagae en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsujiTakehito en-aut-sei=Tsuji en-aut-mei=Takehito 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=National Swine Research Program kn-affil= affil-num=4 en-affil=Faculty of Animal Sciences and Veterinary Medicine, University of Agriculture and Forestry, Hue University kn-affil= affil-num=5 en-affil=Faculty of Animal Sciences and Veterinary Medicine, University of Agriculture and Forestry, Hue 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=Vietnamese native buffalo kn-keyword=Vietnamese native buffalo en-keyword=Nepalese native buffalo kn-keyword=Nepalese native buffalo en-keyword=SNPs kn-keyword=SNPs en-keyword=Reproduction kn-keyword=Reproduction en-keyword=Body growth kn-keyword=Body growth END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=2 article-no= start-page=97 end-page=106 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Atypical lymphoplasmacytic and immunoblastic proliferation: A Systematic Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with autoimmune diseases, but it has not been clearly defined to date. To summarize the histological characteristics and clinical diagnoses associated with ALPIBP, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including “atypical lymphoplasmacytic and immunoblastic lymphadenopathy” from their inception to December 27, 2023. We also summarized the courses of three cases with a pathological diagnosis of ALPIBP. Nine articles with 52 cases were included. Among the total of 55 cases, including the three from our institution, the median age of the cases was 63.5 years with a female predominance (69.5%). Lymphadenopathy was generalized in 65.6% and regional in 34.4% of cases. RA (24.4%), SLE (24.4%), and autoimmune hemolytic anemia (20.0%), were common clinical diagnoses. A combination of cytotoxic chemotherapy was used in 15.6% of cases due to the suspicion of malignancy. Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, methotrexate-associated lymphoproliferative disorders, and IgG4-related diseases were listed as important diseases that need to be pathologically differentiated from ALPIBP. This review summarizes the current understanding of the characteristics of ALPIBP. Given that underrecognition of ALPIBP could lead to overdiagnosis of hematological malignancy and unnecessary treatment, increased awareness of the condition in pathologists and clinicians is crucial. en-copyright= kn-copyright= 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=1 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaokaKensuke en-aut-sei=Takaoka en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MacapagalSharina en-aut-sei=Macapagal en-aut-mei=Sharina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WannaphutChalothorn en-aut-sei=Wannaphut en-aut-mei=Chalothorn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TodaHiroko en-aut-sei=Toda en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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 Medicine, John A. Burns School of Medicine, University of Hawai’i kn-affil= affil-num=3 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i kn-affil= affil-num=4 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i kn-affil= affil-num=5 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i 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 Pathology, Chugoku Central Hospital kn-affil= affil-num=8 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i kn-affil= affil-num=9 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=systematic review kn-keyword=systematic review en-keyword=atypical lymphoplasmacytic and immunoblastic proliferation kn-keyword=atypical lymphoplasmacytic and immunoblastic proliferation en-keyword=IgG4-related disease kn-keyword=IgG4-related disease en-keyword=angioimmunoblastic T-cell lymphoma kn-keyword=angioimmunoblastic T-cell lymphoma END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=e79852 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Presumed Autoimmune Keratitis in Both Eyes Without Systemic Manifestations: A 40-Year Course of a Patient With Corneal Infiltrates and Melt en-subtitle= kn-subtitle= en-abstract= kn-abstract=Peripheral corneal infiltration, corneal ulcer, and melt are recognized complications linked to systemic immunological diseases, such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. These manifestations, which occur in isolation, might be autoimmune keratitis but are difficult to prove underlying immunological abnormalities. This report described a patient with presumed autoimmune keratitis who repeatedly presented corneal infiltration and perforation in both eyes even after penetrating keratoplasty. The 68-year-old patient with a stable condition of keratoconjunctivitis sicca, in a 28-year follow-up, abruptly developed mild infiltrates in the corneal center of the right eye and white dense infiltrates in the peripheral and central cornea of the left eye. He was treated with topical 0.1% betamethasone eye drops and oral prednisolone tapering from 30 mg daily. The patient underwent cataract surgeries in both eyes 10 months after the onset of corneal infiltration and subsequently underwent penetrating keratoplasty in both eyes due to abrupt corneal perforation in the left eye 14 months after the onset of corneal infiltration. Six months post-keratoplasty, he experienced a recurrence of infiltrates in the corneal grafts in both eyes, leading to corneal leukoma in the left eye. The corneal graft in the right eye maintained its integrity with relatively mild opacity until approximately 3.5 years post-keratoplasty, when he abruptly developed white dense infiltration of both the corneal graft and his own peripheral cornea at the age of 73. In response to oral prednisolone tapered from 15 mg daily, the corneal infiltration in the right eye resolved but resulted in graft failure. Since he did not exhibit systemic symptoms and signs throughout the course, the repeat episodes of infiltration in both his own cornea and the corneal graft would be the manifestations of autoimmune keratitis. The entity of autoimmune keratitis in isolation would be beneficial to establish a therapeutic strategy for long-term immunosuppression in light of a risk for steroid side effects and a high rate of corneal graft failure. 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= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=autoimmune keratitis kn-keyword=autoimmune keratitis en-keyword=corneal graft kn-keyword=corneal graft en-keyword=corneal infiltration kn-keyword=corneal infiltration en-keyword=corneal melt kn-keyword=corneal melt en-keyword=penetrating keratoplasty kn-keyword=penetrating keratoplasty END start-ver=1.4 cd-journal=joma no-vol=111 cd-vols= no-issue=6 article-no= start-page=064502 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Josephson effect and odd-frequency pairing in superconducting junctions with unconventional magnets en-subtitle= kn-subtitle= en-abstract= kn-abstract=We consider Josephson junctions formed by coupling two conventional superconductors via an unconventional magnet and investigate the formation of Andreev bound states, their impact on the Josephson effect, and the emergent superconducting correlations. In particular, we focus on unconventional magnets known as ?-wave altermagnets and ?-wave magnets. We find that the Andreev bound states in ?-wave altermagnet and ??-wave magnet Josephson junctions strongly depend on the transverse momentum, with a spin splitting and low-energy minima as a function of the superconducting phase difference ?. In contrast, the Andreev bound states for ??-wave magnets are insensitive to the transverse momentum. We then show that the Andreev bound states can be probed by the local density of states in the middle of the junction, which also reveals that ??2??2- and ?-wave magnet junctions are prone to host zero energy peaks. While the zero-energy peak in ??2??2-wave altermagnet junctions tends to oscillate with the magnetic order, it remains robust in ?-wave magnet junctions. We then discover that the Josephson current in ?-wave altermagnet junctions is composed of higher harmonics of ?, which originate a ?-Josephson junction behavior entirely controlled by the magnetic order in ????-wave altermagnets. In contrast, the Josephson current in Josephson junctions with ?-wave magnets exhibits a conventional sinelike profile with a fast sign change at ?=? due to zero-energy Andreev bound states. We also demonstrate that the critical currents in ?-wave altermagnet Josephson junctions exhibit an oscillatory decay with the increase of the magnetic order, while the oscillations are absent in ?-wave magnet junctions albeit the currents exhibit a slow decay. Furthermore, we also demonstrate that the interplay of the Josephson effect and unconventional magnetic order of ?-wave altermagnets and ?-wave magnets originates from odd-frequency spin-triplet ?-wave superconducting correlations that are otherwise absent. Our results can serve as a guide to pursue the new functionality of Josephson junctions based on unconventional magnets. en-copyright= kn-copyright= en-aut-name=FukayaYuri en-aut-sei=Fukaya en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaKazuki en-aut-sei=Maeda en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YadaKeiji en-aut-sei=Yada en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=CayaoJorge en-aut-sei=Cayao en-aut-mei=Jorge kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaYukio en-aut-sei=Tanaka en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LuBo en-aut-sei=Lu en-aut-mei=Bo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Faculty of Environmental Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Physics, Nagoya University kn-affil= affil-num=3 en-affil=Department of Applied Physics, Nagoya University kn-affil= affil-num=4 en-affil=Department of Physics and Astronomy, Uppsala University kn-affil= affil-num=5 en-affil=Department of Applied Physics, Nagoya University kn-affil= affil-num=6 en-affil=Center for Joint Quantum Studies, Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Department of Physics, Tianjin University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=57 cd-vols= no-issue=2 article-no= start-page=54 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=White coat color in Vietnamese native buffalo is attributed to the LINE1 insertion in ASIP en-subtitle= kn-subtitle= en-abstract= kn-abstract=The coat color of the swamp buffalo is commonly dark gray, while the white coat color variant, which may have potential heat stress advantages, is also present in some Asian countries, including Vietnam. This study analyzed the most likely candidate genes, ASIP and TYR, responsible for the white coat color of Vietnamese native buffaloes. We found that LINE1 insertion in ASIP, a mutation previously reported in white swamp buffalo from other Asian countries, was exclusively found in white Vietnamese buffalo. Moreover, significantly higher expression of ASIP was confirmed in the hair follicles of white buffalo. On the other hand, no variants associated with the white phenotype were found in TYR. These findings indicate that the LINE1 insertion in ASIP is responsible for the white coat color in Vietnamese native buffalo, and that provides a crucial step towards their utilization and improved productivity in Vietnam. en-copyright= kn-copyright= en-aut-name=NguyenThuy Thanh en-aut-sei=Nguyen en-aut-mei=Thuy Thanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LeQuan Viet en-aut-sei=Le en-aut-mei=Quan Viet kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NguyenVan Huu en-aut-sei=Nguyen en-aut-mei=Van Huu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DuongHai Thanh en-aut-sei=Duong en-aut-mei=Hai Thanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiTakehito en-aut-sei=Tsuji en-aut-mei=Takehito 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=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Animal Sciences and Veterinary Medicine, University of Agriculture and Forestry, Hue University kn-affil= affil-num=4 en-affil=Faculty of Animal Sciences and Veterinary Medicine, University of Agriculture and Forestry, Hue University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Vietnamese buffalo kn-keyword=Vietnamese buffalo en-keyword=White coat color kn-keyword=White coat color en-keyword=LINE1 insertion kn-keyword=LINE1 insertion en-keyword=ASIP kn-keyword=ASIP 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=20250217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Kikuchi‐Fujimoto disease: investigating comprehensive clinicopathological features and risk factors for recurrence en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Kikuchi-Fujimoto disease (KFD) is a rare disease that typically manifests with fever and cervical lymphadenopathy. Little is known about the risk factors associated with recurrence and their correlation with clinicopathologic features.
Methods and Results: We analysed 112 patients with KFD, predominantly female (61/112, 54.5%), with an average age of 29.4?years. The incidence was higher in males up to the age of 20 and higher in females from their 30s onwards. Of the 70 patients with follow-up data, 23% experienced recurrence. Recurrence was associated with lower C4 levels (P?=?0.038) and higher antinuclear antibody (ANA) rates (P?=?0.007) compared to transient disease. The mean duration of symptoms was 71.5?days. Lymph node histology in 98 cases (excluding 14 needle biopsy specimens) was classified into three patterns: proliferative (n?=?75, 77%), necrotizing (n?=?22, 22%), and xanthomatous (n?=?1, 1%). The necrotizing pattern associated with significantly enlarged lymph nodes (P?=?0.047) and a longer symptom duration (P?=?0.009) than the proliferating pattern. The number of CD4-positive lymphocytes was significantly lower in the necrotizing type than in the proliferative type (P? Conclusion: These results indicated that low C4 levels and positive ANA were associated with KFD recurrence. Although the aetiology of KFD remains elusive, given that some cases develop autoimmune disease, the results suggest that patients with recurrent KFD represent an intermediate status between those with transient KFD and those with overt autoimmune disease. The comprehensive clinicopathological findings of this study may be useful for elucidating its pathogenesis and predicting the clinical course. en-copyright= kn-copyright= 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=1 ORCID= en-aut-name=SakaoChikako en-aut-sei=Sakao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurokawaYuka en-aut-sei=Kurokawa en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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 General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical 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 Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=histiocytic necrotizing lymphadenitis kn-keyword=histiocytic necrotizing lymphadenitis en-keyword=histological subtypes kn-keyword=histological subtypes en-keyword=Kikuchi-Fujimoto disease kn-keyword=Kikuchi-Fujimoto disease en-keyword=necrotizing type kn-keyword=necrotizing type en-keyword=proliferating type kn-keyword=proliferating type en-keyword=recurrent kn-keyword=recurrent en-keyword=xanthomatous type kn-keyword=xanthomatous type END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=3 article-no= start-page=817 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Interrelationships Between Plasma Levels of Brain Natriuretic Peptide and Prolonged Symptoms Due to Long COVID en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Evidence for the usefulness of biomarkers that aid in diagnosis, assessment of severity, and prediction of prognosis in patients with long COVID is limited. The aim of this study was to clarify the characteristics of brain natriuretic peptide (BNP) in long COVID. Methods: We conducted a retrospective observational study of patients who visited the COVID-19 aftercare outpatient clinic at Okayama University Hospital from February 2021 to April 2024. Results: A total of 428 patients were enrolled in this study, and the patients were divided into a group with normal BNP (n = 314, <= 18.4 pg/mL) and a group with increased BNP (n = 114, >18.4 pg/mL). The long COVID group with increased BNP had a higher proportion of females (44.3% vs. 73.7%, p < 0.01) and an older median age (38 vs. 51 years, p < 0.01). Fatigue and brain fog were commonly manifested in both groups, while dyspnea was a more frequent complaint in the group with increased BNP. Various symptoms including fatigue, palpitations, and taste and/or olfactory disorders were associated with elevated BNP (23 to 24 pg/mL). Memory impairment was also linked to higher BNP (OR: 2.36, p = 0.05). In long COVID patients, plasma BNP elevation appears to be more pronounced in females and is often related to cardiogenic factors, in which inflammatory responses are also involved. Conclusions: Plasma BNP measurement may be useful for evaluating the severity of long COVID, especially in female patients and those with respiratory symptoms and/or memory impairment. en-copyright= kn-copyright= en-aut-name=MasudaYohei en-aut-sei=Masuda en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HondaHiroyuki en-aut-sei=Honda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakuradaYasue en-aut-sei=Sakurada en-aut-mei=Yasue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsudaYui en-aut-sei=Matsuda en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaseRyosuke en-aut-sei=Takase en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OmuraDaisuke en-aut-sei=Omura en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HasegawaToru en-aut-sei=Hasegawa en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UedaKeigo en-aut-sei=Ueda en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=brain fog kn-keyword=brain fog en-keyword=brain natriuretic peptide (BNP) kn-keyword=brain natriuretic peptide (BNP) en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=fatigue kn-keyword=fatigue en-keyword=long COVID kn-keyword=long COVID en-keyword=memory impairment kn-keyword=memory impairment en-keyword=post-COVID-19 conditions kn-keyword=post-COVID-19 conditions END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=16 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Behavior, behavioral syndromes, and metabolism: the effects of artificial selection for death-feigning on metabolic rate en-subtitle= kn-subtitle= en-abstract= kn-abstract=Death-feigning, or thanatosis, is an anti-predator behavioral strategy in many animals. Because individuals remain immobile while feigning death, individuals with longer durations of death feigning often show lower locomotor activity. Thus, metabolic rate, which is closely related to locomotor activity, may also be related to the intensity of death feigning. If there is a genetic correlation between death feigning and metabolism, metabolic rate may respond to selection on death-feigning behavior. Here, we tested for a relationship between metabolic rate and death-feigning using replicated populations of the red flour beetle (Tribolium castaneum) subjected to artificial bidirectional selection on the duration of death-feigning behavior. The results indicated that metabolic rate did not differ between populations selected for increased or decreased death feigning, although locomotor activity was significantly different between these treatments; populations selected for reduced death-feigning durations tended to be more active. These results suggest that death-feigning behavior is not genetically correlated with metabolic rate in T. castaneum. en-copyright= kn-copyright= en-aut-name=MatsumuraKentarou en-aut-sei=Matsumura en-aut-mei=Kentarou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=NodaTomohito en-aut-sei=Noda en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyatakeTakahisa en-aut-sei=Miyatake en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Centre for Ecology and Conservation, Faculty of Environment, Science and Economy, University of Exeter kn-affil= affil-num=3 en-affil=Centre for Ecology and Conservation, Faculty of Environment, Science and Economy, University of Exeter kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Centre for Ecology and Conservation, Faculty of Environment, Science and Economy, University of Exeter kn-affil= en-keyword=anti-predator behavior kn-keyword=anti-predator behavior en-keyword=artificial selection kn-keyword=artificial selection en-keyword=death-feigning kn-keyword=death-feigning en-keyword=metabolic rate kn-keyword=metabolic rate en-keyword=personality kn-keyword=personality en-keyword=Tribolium kn-keyword=Tribolium END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=4 article-no= start-page=563 end-page=567 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Backside Irradiation of Ultraviolet-A for Correcting Nonuniformity Error of Gafchromic XR-QA2 Films en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: Radiochromic film is used for quality assurance and quality control of X-ray equipment in the diagnostic radiology. In addition, three-dimensional dose distribution of computed tomography (CT) is measured. To correct the nonuniformity and uncertainty of radiochromic films for dose measurement of CT, the films are preirradiated ultraviolet (UV)-A rays. There is a difference in the UV protection strength of radiochromic films. A concern exists about the effects of the UV-A irradiation intensity. We thus irradiated with UV-A rays from the backsides of the films to assess if backside irradiation was possible. Materials and Methods: Gafchromic XR-QA2 and RTQA2 were used in this study. The UV-A rays were simultaneously irradiated on the front and backsides of each film for 12 h. The yellow layer of each film was scanned and imaged. The average pixel values ± standard deviations (SDs) were compared. In the statistical analysis, a paired t-test was performed. To compare, the active-layer densities engendered by the UV-A rays. Calibration curve was created with 48 h of preirradiation of UV-A. Results: The mean pixel values ± SD for Gafchromic XR-QA2 on the front and backsides were 130.776 ± 0.812 and 81.015 ± 1.128, respectively. On the other hand, the mean pixel values ± SD for Gafchromic RTQA2 on the front and backsides were 62.299 ± 1.077 and 133.761 ± 1.365, respectively. The statistical results of the paired t-test were significantly different (P < 0.01) between both films. Fitting equation of the calibration curve is shown below. y = -390.47 ± 200 + (443.45 ± 10x80).5068 ± 0.0434. Conclusion: Based on the relationship between the sensitivity of the active layer to UV-A rays and the strength of UV protection on the surface, we concluded that backside irradiation is recommended for Gafchromic XR-QA2, and frontside irradiation is recommended for Gafchromic RTQA2. en-copyright= kn-copyright= en-aut-name=TankiNobuyoshi en-aut-sei=Tanki en-aut-mei=Nobuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GotoSachiko en-aut-sei=Goto en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsudaToshizo en-aut-sei=Katsuda en-aut-mei=Toshizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotandaRumi en-aut-sei=Gotanda en-aut-mei=Rumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotandaTatsuhiro en-aut-sei=Gotanda en-aut-mei=Tatsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuwanoTadao en-aut-sei=Kuwano en-aut-mei=Tadao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medical Radiation Technology, Shizuoka College of Medicalcare Science kn-affil= affil-num=4 en-affil=Department of Radiological Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=6 en-affil=Department of Radiology, Osaka Center for Cancer and Cardiovascular Diseases Prevention kn-affil= en-keyword=Backside irradiation kn-keyword=Backside irradiation en-keyword=computed tomography kn-keyword=computed tomography en-keyword=reflective type radiochromic film kn-keyword=reflective type radiochromic film en-keyword=ultraviolet radiation kn-keyword=ultraviolet radiation 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=20250212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= 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=Background Developmental dyslexia (DD) is a common learning disorder with significant consequences for affected individuals. Although several candidate genes, including dyslexia susceptibility 1 candidate 1 (DYX1C1), have been implicated in dyslexia, their role in brain development remains unclear. We aimed to elucidate the spatiotemporal expression patterns of DYX1C1 during cerebral cortex development in rats.
Methods We investigated DYX1C1 expression during cerebral cortex development using rat embryos at various gestational stages (E13.5, 15.5, 17.5 and 20.5) by immunohistochemistry (n?=?7 embryos/stage), quantitative real-time PCR (n?=?6), and in situ hybridization (n?=?11?15).
Results The DYX1C1-positive cells were predominantly located in the outermost layers of the cortical plate, particularly at E15.5. DYX1C1 mRNA expression peaked at E15.5 and subsequently declined. DYX1C1-positive cells did not co-localize with reelin-positive Cajal-Retzius cells, but co-localized with neuronal markers expressed during development, and had shorter primary cilia than DYX1C1-negative cells.
Conclusions Our findings highlight the dynamic expression of DYX1C1 in the developing cerebral cortex of rats, implicating its involvement in neurodevelopmental processes. Further investigation of the functional interactions of DYX1C1, particularly its relationship with reelin and its role in cerebrocortical and hippocampal development, may provide insights into the pathophysiology of dyslexia and neurodevelopmental disorders. en-copyright= kn-copyright= en-aut-name=ZenshoKazumasa en-aut-sei=Zensho en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IsseAika en-aut-sei=Isse en-aut-mei=Aika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MisawaIchika en-aut-sei=Misawa en-aut-mei=Ichika 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=OkaMakio en-aut-sei=Oka en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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 Psychosocial Medicine, National Center for Child Health and Development kn-affil= affil-num=7 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=99 cd-vols= no-issue=3 article-no= start-page=e02166-24 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A capsidless (+)RNA yadokarivirus hosted by a dsRNA virus is infectious as particles, cDNA, and dsRNA en-subtitle= kn-subtitle= en-abstract= kn-abstract=Capsidless yadokariviruses (members of the order Yadokarivirales) with (+)RNA genomes divert the capsid of their partner icosahedral double-stranded RNA (dsRNA) viruses in different families of the order Ghabrivirales into the replication site. A yadokarivirus, AfSV2, has been reported from a German strain of the ascomycete fungus Aspergillus foetidus coinfected by two dsRNA viruses, a victorivirus (AfSV1, family Pseudototiviridae) and an alternavirus (AfFV, family Alternaviridae). Here, we identified AfSV1 as the partner of AfSV2 in a Japanese A. foetidus strain after showing the infectiousness of AfSV2 in three forms: virus particles (heterocapsid), transforming full-length complementary DNA (cDNA), and purified replicated form (RF) dsRNA that is believed to be inactive as a translational template. Virion transfection of virus-free A. foetidus protoplasts resulted in the generation of two strains infected either by AfSV1 alone or by both AfSV1 and AfSV2. Transformants with AfSV2 full-length cDNA launched AfSV2 infection only in the presence of AfSV1, but not those with AfSV2 RNA-directed RNA polymerase mutant cDNA. The purified fractions containing AfSV2 RF dsRNA also launched infection when transfected into protoplasts infected by AfSV1. Treatment with dsRNA-specific RNase III, but not with proteinase K, S1 nuclease, or DNase I, abolished the infectivity of AfSV2 RF dsRNA. Furthermore, we confirmed the infectiousness of gel-purified AfSV2 RF dsRNA in the presence of AfSV1. Taken together, our results show the unique infectious entity of AfSV2 and the expansion of yadokarivirus partners in the family Pseudototiviridae and provide interesting evolutionary insights. en-copyright= kn-copyright= en-aut-name=FadliMuhammad en-aut-sei=Fadli en-aut-mei=Muhammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisanoSakae en-aut-sei=Hisano en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NovoaGuy en-aut-sei=Novoa en-aut-mei=Guy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Cast?nJos? R. en-aut-sei=Cast?n en-aut-mei=Jos? R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki 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= affil-num=1 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Department of Structure of Macromolecules, Centro Nacional Biotecnolog?a (CNB-CSIC), Campus de Cantoblanco kn-affil= affil-num=4 en-affil=Department of Structure of Macromolecules, Centro Nacional Biotecnolog?a (CNB-CSIC), Campus de Cantoblanco kn-affil= affil-num=5 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=yadokarivirus kn-keyword=yadokarivirus en-keyword=hetero-encapsidation kn-keyword=hetero-encapsidation en-keyword=partner dsRNA virus kn-keyword=partner dsRNA virus en-keyword=fungal virus kn-keyword=fungal virus en-keyword=Aspergillus foetidus kn-keyword=Aspergillus foetidus en-keyword=neo-lifestyle kn-keyword=neo-lifestyle END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=3 article-no= start-page=1007 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the roles of low-density lipoprotein receptor-related protein (LRP) 4 and its ligand Agrin in the pathophysiology of cartilage degeneration. Immunohistochemical analysis of human normal articular cartilage and cartilage tissues from patients with osteoarthritis (OA) obtained during surgery of the knee joint showed marked LRP4 expression in the early stages of OA, which then decreased with cartilage degeneration, whereas Agrin was consistently increased with cartilage degeneration. In normal human articular chondrocytes (NHACs), mild cyclic tensile strain (CTS) (0.5 Hz, 5% elongation, 2 h) increased the expression of LRP4 and aggrecan (ACAN), while intense CTS (0.5 Hz, 10% elongation, 6 h) increased the expression of Agrin without affecting LRP4 expression. Treatment with recombinant human (rh) Agrin downregulated the mRNA expression of LRP4 and ACAN, but upregulated the expression of LRP5/6, SRY-box transcription factor 9 (SOX9), Runt-related transcription factor 2 (RUNX2), and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4). Immunocytochemistry and Western blot analysis showed that rhAgrin treatment upregulated the expression of β-catenin and SOX9. Agrin knockdown by siAGRN transfection partially reduced the nuclear protein expression of β-catenin, which was increased with intense CTS. LRP4 knockdown by siLRP4 transfection increased the expression of LRP5/6, SOX9, RUNX2, ADAMTS-4, and Agrin. These results suggested that intense CTS increases the expression of Agrin, which might interfere with the role of LRP4 in the inhibition of LRP5/6 and their downstream β-catenin signaling, leading to cartilage degeneration. en-copyright= kn-copyright= en-aut-name=NaniwaShuichi en-aut-sei=Naniwa en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NasuYoshihisa en-aut-sei=Nasu en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=HottaYoshifumi en-aut-sei=Hotta en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuNoriyuki en-aut-sei=Shimizu en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IchikawaChinatsu en-aut-sei=Ichikawa en-aut-mei=Chinatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LinDeting en-aut-sei=Lin en-aut-mei=Deting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtsukaNoriaki en-aut-sei=Otsuka en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=2 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=4 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=5 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Sayo Central Hospital kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=osteoarthritis kn-keyword=osteoarthritis en-keyword=chondrocyte kn-keyword=chondrocyte en-keyword=mechanical stress kn-keyword=mechanical stress en-keyword=LRP4 kn-keyword=LRP4 en-keyword=Agrin kn-keyword=Agrin en-keyword=β-catenin kn-keyword=β-catenin en-keyword=SOX9 kn-keyword=SOX9 END start-ver=1.4 cd-journal=joma no-vol=236 cd-vols= no-issue= article-no= start-page=74 end-page=81 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characteristics of porcine oocyte-cumulus complexes derived from various sizes of antral follicles and classified by brilliant cresyl blue staining, and developmental competence of the oocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=The present study sought to determine the characteristics of porcine oocyte-cumulus complexes (OCCs) derived from very small and small antral follicles (with less than 1 mm and 1?3 mm in diameter, respectively; VSF and SF) in comparison with controls from medium ones (with 3?6 mm in diameter; MF). Additionally, the present study examined the utility of brilliant cresyl blue (BCB) staining for assessing these OCCs. The incidence of BCB- oocytes in VSF- and SF-derived OCCs was higher than that in MF-derived OCCs. Although the meiotic and developmental competences of BCB+ oocytes from MF were superior to those from VSF and SF, blastocysts were successfully obtained from BCB+ oocytes even derived from VSF. The mean numbers of both total and viable cumulus cells surrounding an oocyte were significantly affected not only by the origin of the OCCs, but also by the BCB status of the oocytes (largest in MF-derived OCCs containing BCB+ oocytes). Although the outer and inner diameters of zona pellucida were affected by the origin of OCCs and the BCB status of oocytes (largest in MF-derived oocytes), the ooplasmic diameter of BCB+ oocytes did not differ among those derived from VSF, SF, and MF. Regardless of the BCB status, the transcriptional levels of G6PD and TKT in cumulus cells decreased during follicular development from VSF to MF, whereas the RPIA mRNA level in cumulus cells of MF-derived BCB+ OCCs was lower than in the others. These results underscore the utility of BCB staining for selecting MF-, SF-, and even VSF-derived OCCs containing oocytes with relatively higher meiotic and developmental competences, as well as the importance of having a sufficient number of healthy cumulus cells expressing genes related to the pentose phosphate pathway at lower levels. en-copyright= kn-copyright= en-aut-name=VanPhong Ngoc en-aut-sei=Van en-aut-mei=Phong Ngoc kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DoSon Quang en-aut-sei=Do en-aut-mei=Son Quang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FonsekaWanniarachchige Tharindu Lakshitha en-aut-sei=Fonseka en-aut-mei=Wanniarachchige Tharindu Lakshitha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FunahashiHiroaki en-aut-sei=Funahashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=1 article-no= start-page=vvae044 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=The effects of soybeans and its derivatives on oral diseases: a narrative review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Soybean is a widely utilized protein source that originated in China and has been associated with preventing and treating various diseases. Soy protein has been found to inhibit fat accumulation effectively, and soybeans contain isoflavones, saponins, phytic acid, and other substances with preventive and therapeutic effects on heart disease, cancer, and diabetes. Furthermore, processed soybean products, such as Avocado-Soybean unsaponifiable, Tempeh, and Bowman-Birk inhibitor, have demonstrated health benefits. These products have been shown to have antibacterial, antioxidant, and anticancer effects in oral diseases. Numerous experiments have provided evidence of the antibacterial, antioxidant, and anticancer effects of polyunsaturated fatty acids, isoflavones, and soybean polypeptides. This comprehensive review assesses the relationship and mechanism of soybeans and their derivatives on oral diseases, providing valuable insights into their prevention and treatment. en-copyright= kn-copyright= en-aut-name=CanyanKuang en-aut-sei=Canyan en-aut-mei=Kuang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AriasZulema Rosalia en-aut-sei=Arias en-aut-mei=Zulema Rosalia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=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 Pathophysiology?Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathophysiology?Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathophysiology?Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pathophysiology?Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pathophysiology?Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=soybean kn-keyword=soybean en-keyword=soy products kn-keyword=soy products en-keyword=oral diseases kn-keyword=oral diseases en-keyword=dental application kn-keyword=dental application en-keyword=antibacterial effect kn-keyword=antibacterial effect en-keyword=antioxidant kn-keyword=antioxidant en-keyword=anticancer kn-keyword=anticancer 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=20250209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of caffeine on the longevity and locomotion activity of the common green bottle fly, Lucilia sericata (Diptera: Calliphoridae) en-subtitle= kn-subtitle= en-abstract= kn-abstract=The common green bottle fly, Lucilia sericata (Meigen) (Diptera: Calliphoridae), is a promising and useful managed pollinator for greenhouse agricultural crops. The fly can pollinate at lower and higher temperatures than European honeybee. However, management of the longevity of pollinators is important for growers using greenhouses. Previous studies using other insects showed that caffeine affects insect longevity and behaviors. For instance, European honeybee live longer and have increased memory after caffeine consumption. How caffeine affects the longevity and behavior of pollinators is worth investigating because it can affect pollinator’s behavior, extend longevity, or be an insecticide against pollinators. In the present study, therefore, the longevity and locomotion of L. sericata were investigated when they were given different caffeine concentrations. First, the longevity of L. sericata with five different caffeine concentrations was compared to the control. The results showed that higher concentrations of caffeine (2%, 1%, and 0.5%) significantly decreased the life span compared to lower concentrations (0.05% and 0.01%). Second, the locomotion activities of L. sericata were examined at those two caffeine concentrations with treated and control male and female flies utilizing a Drosophila Activity Monitor (DAM). Treatment with 0.05% caffeine dramatically reduced locomotion, but treatment of 0.01% caffeine did not. We also compared lipid concentrations of flies: flies treated with 0.05% caffeine had a lower lipid concentration compared to flies treated with 0% and 0.01% caffeine. These results indicate that caffeine had negative effects on the longevity and locomotion activities of the pollinator L. sericata in laboratory conditions. en-copyright= kn-copyright= en-aut-name=NaingShine Shane en-aut-sei=Naing en-aut-mei=Shine Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiokaHaruna en-aut-sei=Fujioka en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuuraTeruhisa en-aut-sei=Matsuura en-aut-mei=Teruhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyatakeTakahisa en-aut-sei=Miyatake en-aut-mei=Takahisa 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Caffeine kn-keyword=Caffeine en-keyword=Life span kn-keyword=Life span en-keyword=Locomotor activity kn-keyword=Locomotor activity en-keyword=Pollinator kn-keyword=Pollinator END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue= article-no= start-page=103026 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=The antimalarial activity of transdermal N-89 mediated by inhibiting ERC gene expression in P. Berghei-infected mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Through studies of new antimalarial drugs, we identified 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) as a potential drug candidate. Here, we analyzed the antimalarial action of a transdermal formulation (td) of N-89, designed for easy use by children, using Plasmodium berghei-infected mice as a model for malaria patients. The td N-89 or artemisinin (ART) formulation was transdermally administered to P. berghei-infected mice with 0.2?0.4 % parasitemia, twice daily for four days, at an effective dose of 90 % for malaria. Parasitemia was decreased in td N-89 and td ART groups during the drug treatment; then, three of the eight mice in td N-89 group were completely cured without relapse. Additionally, abnormal trophozoites in td N-89 group were observed 8 h after administration and increased up to 24 h. To study the change in endoplasmic reticulum-resident calcium-binding protein (ERC) gene expression with td N-89, we investigated the gene expression of P. berghei ERC (PbERC) after td N-89 treatment. PbERC gene expression was increased time-dependently in control group, and was statistically decreased at 4 and 8 h and then increased similar to that of control group at 12 h in td ART group. In contrast, the expression in td N-89 group was almost steady starting from 0 h. We also studied parasite egress-related genes expression after td N-89 treatment, plasmepsin X, subtilisin-like protease 1 and merozoite surface protein 1, were suppressed at 12 h compared to control group. These results suggest that N-89 affects function of endoplasmic reticulum via regulating gene suppression and subsequently parasite growth is inhibited. en-copyright= kn-copyright= en-aut-name=MatsumoriHiroaki en-aut-sei=Matsumori en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DinhThi Quyen en-aut-sei=Dinh en-aut-mei=Thi Quyen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoritaMasayuki en-aut-sei=Morita en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimHye-Sook en-aut-sei=Kim en-aut-mei=Hye-Sook kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Research Center for Intestinal Health Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Anatomy, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Division of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Synthetic antimalarial endoperoxide kn-keyword=Synthetic antimalarial endoperoxide en-keyword=Transdermal N-89 kn-keyword=Transdermal N-89 en-keyword=Artemisinin kn-keyword=Artemisinin en-keyword=In vivo kn-keyword=In vivo en-keyword=Abnormal trophozoite kn-keyword=Abnormal trophozoite en-keyword=Endoplasmic reticulum-resident calcium-binding protein (ERC) kn-keyword=Endoplasmic reticulum-resident calcium-binding protein (ERC) en-keyword=Parasite egress-related gene kn-keyword=Parasite egress-related gene END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=24 article-no= start-page=4606 end-page=4620 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=Nano/microparticle-based tough and recyclable polymers toward a sustainable society en-subtitle= kn-subtitle= en-abstract= kn-abstract=By virtue of their unique properties, polymer nano/microparticles constitute important building blocks for the construction of functional nanomaterials. Although intense research efforts in this field have laid the foundation for the applications of polymer nano/microparticle-based latex films, cutting-edge innovations in the recycling of polymer materials are still required for the realization of a sustainable society. This feature article reviews our recent attempts to develop the applications of polymer nano/microparticles in the context of a circular society on the basis of the precise synthesis of single nano/microparticles and multiscale structural analysis. en-copyright= kn-copyright= en-aut-name=SasakiYuma en-aut-sei=Sasaki en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishizawaYuichiro en-aut-sei=Nishizawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurehaTakuma en-aut-sei=Kureha en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiDaisuke en-aut-sei=Suzuki en-aut-mei=Daisuke 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=Department of Frontier Materials Chemistry, Graduate School of Science and Technology, Hirosaki University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=2 article-no= start-page=376 end-page=382 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case of pancreatic ductal adenocarcinoma growing within the pancreatic duct mimicking an intraductal tubulopapillary neoplasm en-subtitle= kn-subtitle= en-abstract= kn-abstract=We herein report a case of pancreatic ductal adenocarcinoma (PDAC) that developed within the pancreatic duct and was initially diagnosed as an intraductal tubulopapillary neoplasm (ITPN). A 76-year-old man presented with weight loss and main pancreatic duct dilation. The imaging studies revealed a 30-mm hypovascular tumor within the main duct of the pancreatic head. An endoscopic examination with a biopsy revealed high-grade atypical epithelial cells with immunostaining patterns suggestive of ITPN. Following robot-assisted pancreaticoduodenectomy, postoperative pathology revealed conflicting features: nodular/cribriform infiltrations typical of ITPN and non-lobular replacement with scattered infiltrations characteristic of PDAC. A comprehensive genomic profiling test detected KRAS and TP53 mutations, leading to the final diagnosis of PDAC (fT3N1aM0, stage IIB). The patient received adjuvant S-1 chemotherapy and remained recurrence-free for 15 months post-surgery. This case highlights the diagnostic challenges of differentiating intraductal pancreatic tumors and demonstrates the utility of integrating genetic testing with conventional diagnostic modalities for an accurate diagnosis and appropriate treatment selection. en-copyright= kn-copyright= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke 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=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=NishidaKenji en-aut-sei=Nishida en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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 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 Radiology, 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 Pathology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Pathology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=Pancreatic intraductal neoplasms kn-keyword=Pancreatic intraductal neoplasms en-keyword=Pancreatic carcinoma kn-keyword=Pancreatic carcinoma en-keyword=Intraductal tubulopapillary neoplasm kn-keyword=Intraductal tubulopapillary neoplasm en-keyword=Genetic testing kn-keyword=Genetic testing END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=1 article-no= start-page=59 end-page=64 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=A Rare Case of Compression Neuritis due to Intraorbital Arteriovenous Fistula (IOAVF) Mimicking Retrobulbar Optic Neuritis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intraorbital arteriovenous fistulas (IOAVFs) are rare vascular abnormalities. We describe a case of an IOAVF featuring a direct shunt between the accessory meningeal artery and the superior ophthalmic artery. A 55-year-old woman presented with a 1-month history of visual impairment in her right eye, and magnetic resonance imaging (MRI) revealed optic neuritis-like findings. Steroid pulse therapy temporarily resolved visual impairment. However, 1 month later, she experienced decreased visual acuity, ocular conjunctival hyperemia, edema, and a pulsatile murmur. Contrast-enhanced MRI and digital subtraction angiography revealed compression optic neuropathy due to an IOAVF. Following successful treatment with transarterial embolization, her symptoms disappeared. en-copyright= kn-copyright= en-aut-name=MinakawaShun en-aut-sei=Minakawa en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiranoMasayuki en-aut-sei=Hirano en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiKazuya en-aut-sei=Takahashi en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImamuraYuta en-aut-sei=Imamura en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeTakashi en-aut-sei=Watanabe en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Japanese Red Cross Society Himeji Hospital kn-affil= en-keyword=intraorbital arteriovenous fistula kn-keyword=intraorbital arteriovenous fistula en-keyword=compressive optic neuropathy kn-keyword=compressive optic neuropathy en-keyword=accessory meningeal artery kn-keyword=accessory meningeal artery en-keyword=superior ophthalmic vein kn-keyword=superior ophthalmic vein END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=1 article-no= start-page=51 end-page=58 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=Photoinitiators Induce Histamine Production in Human Mast Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photoinitiators are used in the manufacture of many daily products, and may produce harmful effects due to their cytotoxicity. They have also been detected in human serum. Here, we investigated the histamine-producing effects in HMC-1 cells and the inflammatory cytokine release effects in RAW264 cells for four photoinitiators: 1-hydroxycyclohexyl phenyl ketone; 2-isopropylthioxanthone; methyl 2-benzoylbenzoate; and 2-methyl-4´-(methylthio)-2-morpholinopropiophenone. All four promoted histamine production in HMC-1 cells; however, they did not significantly affect the release of inflammatory cytokines in RAW264 cells. These findings suggest that these four photoinitiators induce inflammatory cytokine-independent histamine production, potentially contributing to histamine-mediated chronic inflammation in vitro. en-copyright= kn-copyright= en-aut-name=MiuraTaro en-aut-sei=Miura en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawasakiYoichi en-aut-sei=Kawasaki en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=SendoToshiaki en-aut-sei=Sendo en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Laboratory of Clinical Pharmacology and Therapeutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=photoinitiator kn-keyword=photoinitiator en-keyword=ink kn-keyword=ink en-keyword=injection kn-keyword=injection en-keyword=histamine kn-keyword=histamine en-keyword=inflammation kn-keyword=inflammation END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=3 article-no= start-page=96 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer-associated fibroblasts promote pro-tumor functions of neutrophils in pancreatic cancer via IL-8: potential suppression by pirfenidone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The mechanisms by which neutrophils acquire pro-tumor properties remain poorly understood. In pancreatic cancer, cancer-associated fibroblasts (CAFs) may interact with neutrophils, directing them to promote tumor progression.
Methods To validate the association between CAFs and neutrophils, the localization of neutrophils was examined in clinically resected pancreatic cancer specimens. CAFs were produced by culturing in cancer-conditioned media, and the effects of these CAFs on neutrophils were examined. In vitro migration and invasion assays assess the effect of CAF-activated neutrophils on cancer cells. The factors secreted by the activated neutrophils were also explored. Finally, pirfenidone (PFD) was tested to determine whether it could suppress the pro-tumor functions of activated neutrophils.
Results In pancreatic cancer specimens, neutrophils tended to co-localize with IL-6-positive CAFs. Neutrophils co-cultured with CAFs increased migratory capacity and prolonged life span. CAF-affected neutrophils enhance the migratory and invasive activities of pancreatic cancer cells. IL-8 is the most upregulated cytokine secreted by the neutrophils. PFD suppresses IL-8 secretion from CAF-stimulated neutrophils and mitigates the malignant traits of pancreatic cancer cells.
Conclusion CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach. en-copyright= kn-copyright= en-aut-name=YagiTomohiko en-aut-sei=Yagi en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NogiShohei en-aut-sei=Nogi en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniguchiAtsuki en-aut-sei=Taniguchi en-aut-mei=Atsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimotoMasashi en-aut-sei=Yoshimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuemoriKanto en-aut-sei=Suemori en-aut-mei=Kanto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujitaShuto en-aut-sei=Fujita en-aut-mei=Shuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Neutrophil kn-keyword=Neutrophil en-keyword=Anti-fibrotic agent kn-keyword=Anti-fibrotic agent en-keyword=Pirfenidone kn-keyword=Pirfenidone END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=1 article-no= start-page=21 end-page=30 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=Prediction of Prostate Cancer Grades Using Radiomic Features en-subtitle= kn-subtitle= en-abstract= kn-abstract=We developed a machine learning model for predicting prostate cancer (PCa) grades using radiomic features of magnetic resonance imaging. 112 patients diagnosed with PCa based on prostate biopsy between January 2014 and December 2021 were evaluated. Logistic regression was used to construct two prediction models, one using radiomic features and prostate-specific antigen (PSA) values (Radiomics model) and the other Prostate Imaging-Reporting and Data System (PI-RADS) scores and PSA values (PI-RADS model), to differentiate high-grade (Gleason score [GS] ? 8) from intermediate or low-grade (GS < 8) PCa. Five imaging features were selected for the Radiomics model using the Gini coefficient. Model performance was evaluated using AUC, sensitivity, and specificity. The models were compared by leave-one-out cross-validation with Ridge regularization. Furthermore, the Radiomics model was evaluated using the holdout method and represented by a nomogram. The AUC of the Radiomics and PI-RADS models differed significantly (0.799, 95% CI: 0.712-0.869; and 0.710, 95% CI: 0.617-0.792, respectively). Using holdout method, the Radiomics model yielded AUC of 0.778 (95% CI: 0.552-0.925), sensitivity of 0.769, and specificity of 0.778. It outperformed the PI-RADS model and could be useful in predicting PCa grades, potentially aiding in determining appropriate treatment approaches in PCa patients. en-copyright= kn-copyright= en-aut-name=YamamotoYasuhiro en-aut-sei=Yamamoto en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraguchiTakafumi en-aut-sei=Haraguchi en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsudaKaori en-aut-sei=Matsuda en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkazakiYoshio en-aut-sei=Okazaki en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimotoShin en-aut-sei=Kimoto en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanjiNozomu en-aut-sei=Tanji en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoAtsushi en-aut-sei=Matsumoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=MimuraHidefumi en-aut-sei=Mimura en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil=Department of Radiology, Houshasen Daiichi Hospital kn-affil= affil-num=2 en-affil=Department of Advanced Biomedical Imaging and Informatics, St. Marianna University School of Medicine kn-affil= affil-num=3 en-affil=Department of Radiology, Houshasen Daiichi Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Houshasen Daiichi Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Houshasen Daiichi Hospital kn-affil= affil-num=6 en-affil=Department of Urology, Houshasen Daiichi Hospital kn-affil= affil-num=7 en-affil=Department of Urology, Houshasen Daiichi Hospital kn-affil= affil-num=8 en-affil=Department of Medical Information and Communication Technology Research, St. Marianna University School of Medicine kn-affil= affil-num=9 en-affil=Department of Radiology, St. Marianna University School of Medicine kn-affil= affil-num=10 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=prostate cancer kn-keyword=prostate cancer en-keyword=machine learning kn-keyword=machine learning en-keyword=prostate Imaging-Reporting and Data System kn-keyword=prostate Imaging-Reporting and Data System en-keyword=radiomics kn-keyword=radiomics en-keyword=Gleason score kn-keyword=Gleason score END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=1 article-no= start-page=1 end-page=7 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=Endothelial Cell Polarity in Health and Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Endothelial cell polarity is fundamental to the organization and function of blood vessels, influencing processes such as angiogenesis, vascular stability, and response to shear stress. This review elaborates on the molecular mechanisms that regulate endothelial cell polarity, focusing on key players like the PAR polarity complex and Rho family GTPases. These pathways coordinate the front?rear, apical?basal and planar polarity of endothelial cells, which are essential for the proper formation and maintenance of vascular structures. In health, endothelial polarity ensures not only the orderly development of blood vessels, with tip cells adopting distinct polarities during angiogenesis, but also ensures proper vascular integrity and function. In disease states, however, disruptions in polarity contribute to pathologies such as coronary artery disease, where altered planar polarity exacerbates atherosclerosis, and cancer, where disrupted polarity in tumor vasculature leads to abnormal vessel growth and function. Understanding cell polarity and its disruption is fundamental not only to comprehending how cells interact with their microenvironment and organize themselves into complex, organ-specific tissues but also to developing novel, targeted, and therapeutic strategies for a range of diseases, from cardiovascular disorders to malignancies, ultimately improving patient outcomes. en-copyright= kn-copyright= en-aut-name=ThihaMoe en-aut-sei=Thiha en-aut-mei=Moe 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=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=blood vessel kn-keyword=blood vessel en-keyword=endothelial cell kn-keyword=endothelial cell en-keyword=cell polarity kn-keyword=cell polarity en-keyword=atherosclerosis kn-keyword=atherosclerosis en-keyword=cancer kn-keyword=cancer END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=1 article-no= start-page=1 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relationships between tilt angles of rectus muscles and positions of rectus muscle pulleys in patients with sagging eye syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose To examine the relationship between the rectus muscle (RM) angle and RM pulley displacement in patients with sagging eye syndrome (SES) without myopia.
Study design Retrospective cross-sectional case series.
Methods High-resolution quasi-coronal magnetic resonance imaging (MRI) data from 20 orbits of ten Japanese patients with SES but without high myopia were analyzed. The patients had no abduction deficiency. The RM angles were measured between the major axes of the horizontal and vertical RMs relative to the vertical and horizontal planes, respectively. The positions of the RM pulleys relative to the center of the globe were analyzed as previously described.
Results The mean age of the patients was 75.8 ± 4.5 years (standard deviation). The average axial length was 23.6 ± 0.6 mm. The lateral rectus (LR) muscle angle (22 ± 6°) had moderate negative correlations with the inferior displacement of the inferior rectus (IR), superior rectus (SR), and LR pulleys (r =? 0.63,? 0.45, and? 0.45, respectively); however, no change was observed in the medial rectus (MR) pulley (r =? 0.41). No correlations were found between the angles of the SR (4 ± 8°), IR (? 13 ± 8°), and MR (? 1 ± 6°) muscles and the positions of the RM pulleys.
Conclusion Given the correlation between increased LR muscle angle and inferior displacement of adjacent RM pulleys in SES, the LR muscle angle may serve as a diagnostic clue, even when inferior displacement is not identifiable on MRI. Further confirmation in larger studies is warranted. en-copyright= kn-copyright= en-aut-name=KonoReika en-aut-sei=Kono en-aut-mei=Reika 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=KishimotoFumiko en-aut-sei=Kishimoto en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=Division of Ophthalmology, Ibara City Hospital, Ibara City 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= en-keyword=Orbital pulley kn-keyword=Orbital pulley en-keyword=Sagging eye syndrome kn-keyword=Sagging eye syndrome en-keyword=Distance esotropia kn-keyword=Distance esotropia en-keyword=Cyclovertical strabismus kn-keyword=Cyclovertical strabismus en-keyword=Aging kn-keyword=Aging END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=35 article-no= start-page=e2320189121 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240821 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) exert clinical efficacy against various types of cancers by reinvigorating exhausted CD8+ T cells that can expand and directly attack cancer cells (cancer-specific T cells) among tumor-infiltrating lymphocytes (TILs). Although some reports have identified somatic mutations in TILs, their effect on antitumor immunity remains unclear. In this study, we successfully established 18 cancer-specific T cell clones, which have an exhaustion phenotype, from the TILs of four patients with melanoma. We conducted whole-genome sequencing for these T cell clones and identified various somatic mutations in them with high clonality. Among the somatic mutations, an SH2D2A loss-of-function frameshift mutation and TNFAIP3 deletion could activate T cell effector functions in vitro. Furthermore, we generated CD8+ T cell?specific Tnfaip3 knockout mice and showed that Tnfaip3 function loss in CD8+ T cell increased antitumor immunity, leading to remarkable response to PD-1 blockade in vivo. In addition, we analyzed bulk CD3+ T cells from TILs in additional 12 patients and identified an SH2D2A mutation in one patient through amplicon sequencing. These findings suggest that somatic mutations in TILs can affect antitumor immunity and suggest unique biomarkers and therapeutic targets. en-copyright= kn-copyright= en-aut-name=MukoharaFumiaki en-aut-sei=Mukohara en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwataKazuma en-aut-sei=Iwata en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=UenoToshihide en-aut-sei=Ueno en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkedaHideki en-aut-sei=Ikeda en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaseKatsushige en-aut-sei=Kawase en-aut-mei=Katsushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaekiYuka en-aut-sei=Saeki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamashitaKazuo en-aut-sei=Yamashita en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawaharaYu en-aut-sei=Kawahara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WatanabeHiroko en-aut-sei=Watanabe en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DansakoHiromichi en-aut-sei=Dansako en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SuzukiYutaka en-aut-sei=Suzuki en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HondaHiroaki en-aut-sei=Honda en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 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=23 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 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=25 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University kn-affil= affil-num=8 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=9 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=10 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=11 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=13 en-affil=KOTAI Biotechnologies, Inc. kn-affil= affil-num=14 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=16 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=17 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=19 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=20 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa kn-affil= affil-num=21 en-affil=Department of Pathology, Tokyo Women's Medical University kn-affil= affil-num=22 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=23 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University kn-affil= affil-num=24 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=25 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cancer immunology kn-keyword=cancer immunology en-keyword=somatic mutation kn-keyword=somatic mutation en-keyword=T cell kn-keyword=T cell en-keyword=tumor-infiltrating lymphocytes kn-keyword=tumor-infiltrating lymphocytes END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=2485 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cesarean delivery on child health and development in Japanese nationwide birth cohort en-subtitle= kn-subtitle= en-abstract= kn-abstract=The long-term effects of cesarean delivery (CD) on child health and development remain controversial. This study aimed to investigate these effects using an outcome-wide approach in a Japanese context, where perinatal mortality rates are among the world's lowest. We analyzed data from 2,114 children in a nationwide Japanese birth cohort, linking the 21st Century Longitudinal Survey of Newborns with the Perinatal Research Network database. We examined associations between CD and various health and developmental outcomes up to 9 years of age, including hospitalizations, obesity, and developmental milestones. After adjusting for potential confounders, CD was not significantly associated with most outcomes, including all-cause hospitalization (adjusted risk ratio 1.25, 95% CI 0.997-1.56), obesity at 5.5 and 9 years, and various developmental milestones. Subgroup analyses for multiple births and preterm infants showed some differences in point estimates, but were limited by small sample sizes. CD was not significantly associated with adverse long-term child health or developmental outcomes in this Japanese cohort. These findings provide reassurance regarding CD safety when medically indicated in advanced perinatal care settings. Further research with larger samples and longer follow-up is needed, especially for specific subgroups. en-copyright= kn-copyright= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitsuiTakashi en-aut-sei=Mitsui en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TamaiKei en-aut-sei=Tamai en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirotaTomoya en-aut-sei=Hirota en-aut-mei=Tomoya 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=YorifujiTakashi en-aut-sei=Yorifuji 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 Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Neonatology, NHO Okayama Medical Center kn-affil= affil-num=4 en-affil=Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California San Francisco kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cesarean delivery kn-keyword=Cesarean delivery en-keyword=Delivery methods kn-keyword=Delivery methods en-keyword=Long-term outcome kn-keyword=Long-term outcome en-keyword=Child development kn-keyword=Child development en-keyword=Outcome-wide approach kn-keyword=Outcome-wide approach END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=2 article-no= start-page=e70168 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Crowned Dens Syndrome Triggered by Dental Treatment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Crowned dens syndrome (CDS) is an important yet often overlooked cause of fever and neck pain, frequently leading to unnecessary examinations and treatments and misdiagnosis as infectious diseases or rheumatic diseases. The mechanism of an acute attack of CDS is not clarified completely, while it is considered that severe systemic stress can trigger inflammation caused by calcium pyrophosphate crystals. We describe a case of CDS triggered by localized physical stress to the neck and emphasize the importance of considering this condition in cases of fever and neck pain following dental treatment. en-copyright= kn-copyright= en-aut-name=MoritaSatoru en-aut-sei=Morita en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MasudaYohei en-aut-sei=Masuda en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SoejimaYoshiaki en-aut-sei=Soejima en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=calcium pyrophosphate crystal deposition disease kn-keyword=calcium pyrophosphate crystal deposition disease en-keyword=crowned dens syndrome kn-keyword=crowned dens syndrome en-keyword=dental treatment kn-keyword=dental treatment en-keyword=fever kn-keyword=fever en-keyword=neck pain kn-keyword=neck pain END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=e70062 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trends in uptake of cancer screening among people with severe mental illness before and after the COVID-19 pandemic in Japan: A repeated cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: The aim of this study was to investigate trends in cancer screening participation among people with severe mental illness (PSMI) from periods before and after the COVID-19 pandemic.
Methods: In this repeated cross-sectional study, we used anonymized datasets on municipal cancer screening participation among PSMI in Okayama City. The data covered fiscal year (FY) 2018 to FY2022; we used the municipal cancer screening database and Medical Payment for Services and Supports for Persons with Disabilities. PSMI were defined as those with schizophrenia or related psychotic disorders (F20-29) or bipolar disorder (F30 or F31), identified using International Classification of Diseases, Tenth Revision, codes. The analysis included men and women aged 40-69 years for colorectal and lung cancer screening; men and women aged 50-69 years for gastric cancer screening; women aged 40-69 years for breast cancer screening; and women aged 20-69 years for cervical cancer screening. Municipal cancer screening rates among PSMI were calculated for each FY.
Results: For all cancer types, cancer screening rates for PSMI in FY2020 (colorectal: 9.0%; lung: 11.6%; gastric: 4.9%; breast: 6.2%; and cervical: 6.1%) were lower than the rates in FY2019 (11.5%, 14.0%, 6.5%, 9.3%, and 8.3%, respectively). In FY2022, the rates (9.9%, 12.9%; 5.3%; 8.0%, and 6.9%, respectively) recovered, but remained low.
Conclusion: This study showed that cancer screening rates among PSMI were very low, both before and after the COVID-19 pandemic. Efforts to encourage participation in cancer screening in this population are urgently needed. en-copyright= kn-copyright= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayaNaoki en-aut-sei=Nakaya en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukiKoji en-aut-sei=Otsuki en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimazuTaichi en-aut-sei=Shimazu en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimoriMaiko en-aut-sei=Fujimori en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HinotsuShiro en-aut-sei=Hinotsu en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagoshiKiwamu en-aut-sei=Nagoshi en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchitomiYosuke en-aut-sei=Uchitomi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InagakiMasatoshi en-aut-sei=Inagaki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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 Hospital kn-affil= affil-num=3 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=4 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= affil-num=5 en-affil=Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=6 en-affil=Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=7 en-affil=Department of Biostatistics and Data Management, Sapporo Medical University kn-affil= affil-num=8 en-affil=Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University kn-affil= affil-num=9 en-affil=Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine kn-affil= affil-num=10 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= en-keyword=bipolar disorder kn-keyword=bipolar disorder en-keyword=cancer screening kn-keyword=cancer screening en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=healthcare disparities kn-keyword=healthcare disparities en-keyword=schizophrenia kn-keyword=schizophrenia END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=RP99858 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural basis for molecular assembly of fucoxanthin chlorophyll a/c-binding proteins in a diatom photosystem I supercomplex en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosynthetic organisms exhibit remarkable diversity in their light-harvesting complexes (LHCs). LHCs are associated with photosystem I (PSI), forming a PSI-LHCI supercomplex. The number of LHCI subunits, along with their protein sequences and pigment compositions, has been found to differ greatly among the PSI-LHCI structures. However, the mechanisms by which LHCIs recognize their specific binding sites within the PSI core remain unclear. In this study, we determined the cryo-electron microscopy structure of a PSI supercomplex incorporating fucoxanthin chlorophyll a/c-binding proteins (FCPs), designated as PSI-FCPI, isolated from the diatom Thalassiosira pseudonana CCMP1335. Structural analysis of PSI-FCPI revealed five FCPI subunits associated with a PSI monomer; these subunits were identified as RedCAP, Lhcr3, Lhcq10, Lhcf10, and Lhcq8. Through structural and sequence analyses, we identified specific protein-protein interactions at the interfaces between FCPI and PSI subunits, as well as among FCPI subunits themselves. Comparative structural analyses of PSI-FCPI supercomplexes, combined with phylogenetic analysis of FCPs from T. pseudonana and the diatom Chaetoceros gracilis, underscore the evolutionary conservation of protein motifs crucial for the selective binding of individual FCPI subunits. These findings provide significant insights into the molecular mechanisms underlying the assembly and selective binding of FCPIs in diatoms. en-copyright= kn-copyright= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=XingJian en-aut-sei=Xing en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KumazawaMinoru en-aut-sei=Kumazawa en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgawaHaruya en-aut-sei=Ogawa en-aut-mei=Haruya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IfukuKentaro en-aut-sei=Ifuku en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagaoRyo en-aut-sei=Nagao en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama 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=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=8 en-affil=Faculty of Agriculture, Shizuoka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=e70073 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy and safety of endoscopic ultrasonography-guided radiofrequency ablation of small pancreatic neuroendocrine neoplasms: A prospective, pilot study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Endoscopic ultrasonography (EUS)-guided radiofrequency ablation has recently been introduced as one of the management strategies for small pancreatic neuroendocrine neoplasms (PNENs). However, prospective data on its safety and efficacy remain limited.
Methods: This prospective pilot study was conducted at Okayama University Hospital from May 2023 to December 2024. Patients with grade 1 PNENs <= 15 mm, confirmed by EUS-guided fine-needle aspiration, were included. The primary endpoint was safety (adverse events [AEs] evaluated according to the 2010 guidelines of the American Society for Gastrointestinal Endoscopy. Severe AEs were defined as moderate or higher in American Society for Gastrointestinal Endoscopy grading and grade >= 3. Secondary endpoints included efficacy (complete response on contrast-enhanced computed tomography at 1 and 6 months), treatment details, device failure, diabetes mellitus exacerbation, and overall survival at 6 months.
Results: Five patients with non-functional PNENs (median age: 64 years; median tumor size: 10 mm) were treated. AEs occurred in two patients (40%, 2/5), although none was severe. Both patients developed asymptomatic pseudocysts, one experienced mild pancreatitis, and both resolved with conservative treatment. The complete response rates on contrast-enhanced computed tomography at one and 6 months were 100%. The median procedure time was 16 min without any device failure, and the median hospitalization was 5 days. None of the patients developed new-onset or worsening diabetes mellitus. The 6-month overall survival rate was 100%.
Conclusion: EUS-guided radiofrequency ablation demonstrated a high complete response rate with no severe AEs in this pilot study, suggesting a minimally invasive option for small, low-grade PNENs (jRCTs062230014). en-copyright= kn-copyright= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeuchiYasuto en-aut-sei=Takeuchi en-aut-mei=Yasuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=HaradaKei en-aut-sei=Harada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HattoriNao en-aut-sei=Hattori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ObataTaisuke en-aut-sei=Obata en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=HaradaRyo en-aut-sei=Harada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiiMasakuni en-aut-sei=Fujii en-aut-mei=Masakuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University 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 Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=16 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=ablation techniques kn-keyword=ablation techniques en-keyword=endosonography kn-keyword=endosonography en-keyword=neuroendocrine tumors kn-keyword=neuroendocrine tumors en-keyword=pancreatic neoplasms kn-keyword=pancreatic neoplasms en-keyword=pilot projects kn-keyword=pilot projects END start-ver=1.4 cd-journal=joma no-vol=114 cd-vols= no-issue= article-no= start-page=27 end-page=38 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The List of Published by Members of the Faculty From January to December 2024. kn-title=公表学術論文等リスト　2024 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=114 cd-vols= no-issue= article-no= start-page=21 end-page=25 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Elucidation of plant-bacterial pathogen interactions for the control of bacterial blight on cruciferous crops kn-title=アブラナ科植物黒斑細菌病の防除に向けた植物−病原細菌の相互作用の解明 en-subtitle= kn-subtitle= en-abstract= kn-abstract=　Pseudomonas cannabina pv. alisalensis (Pcal), the causative agent of bacterial blight on cruciferous crops, is an economically important pathogen worldwide. We have conducted several studies on the interactions between plants and pathogenic bacteria to develop effective control strategies for this disease. Using forward and reverse genetics, we identified several virulence factors, including the type III secretion system, membrane transporters, transcriptional factors, and amino acid metabolism. Additionally, we emphasized the role of coronatine, a toxin produced by Pcal, which promotes stomatal reopening and suppresses salicylic acid accumulation in plants. We also examined plant defense mechanisms activated by one of the plant defense activators, acibenzolar-S-methyl (ASM). ASM enhanced stomatal-based defense, resulting in reduction of bacterial entry and disease development. Moreover, we explored innovative control strategies for bacterial disease and demonstrated that amino acids and cellulose nanofiber are efficient and environmentally friendly control strategies. These studies advance our understanding of plant-pathogen dynamics and offer promising, sustainable approaches for managing bacterial blight disease in cruciferous crops. en-copyright= kn-copyright= en-aut-name=SakataNanami en-aut-sei=Sakata en-aut-mei=Nanami kn-aut-name=坂田七海 kn-aut-sei=坂田 kn-aut-mei=七海 aut-affil-num=1 ORCID= affil-num=1 en-affil=Course of Applied Plant Science kn-affil=応用植物科学コース en-keyword=Plant pathogenic bacteria kn-keyword=Plant pathogenic bacteria en-keyword=Pseudomonas kn-keyword=Pseudomonas en-keyword=Cruciferous kn-keyword=Cruciferous en-keyword=Plant protection kn-keyword=Plant protection en-keyword=Stomata kn-keyword=Stomata END start-ver=1.4 cd-journal=joma no-vol=114 cd-vols= no-issue= article-no= start-page=11 end-page=20 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Uncovering the role of arcuate kisspeptin neurons as a source of the gonadotropin-releasing hormone pulse generator using gene-modified rats kn-title=遺伝子改変ラットを用いた弓状核キスペプチンニューロンの性腺刺激ホルモン放出ホルモンパルスジェネレーターとしての役割解明 en-subtitle= kn-subtitle= en-abstract=　世界において，乳牛の受胎率（妊娠率）が低下しており，家畜の繁殖成績向上のための効果的な治療法が必要とされている．家畜を含む哺乳類において，生殖機能は視床下部−下垂体−性腺軸から分泌されるホルモンによって制御されている．これらのホルモンのうち，性腺刺激ホルモン放出ホルモン（GnRH）のパルス状分泌（GnRH パルス）は，性腺刺激ホルモン分泌と性腺機能に本質的に重要である．したがって，GnRH パルスを制御するメカニズム（GnRH パルスジェネレーター）を解明することは，家畜の生殖技術を向上させるために不可欠である．本総説では，著者らの遺伝子改変ラットモデルを用いた弓状核キスペプチンニューロン（ΚNDy ニューロンとしても知られる）がGnRH パルスジェネレーターの本体であることの直接的な証拠を示した研究を中心として，過去20年間の研究を概説した．また，ΚNDy ニューロンが分泌するニューロキニンB，グルタミン酸，ダイノルフィンA がΚNDy ニューロンの神経活動を同期させ，GnRH パルスを発生させるメカニズムについて論じた．遺伝子改変ラットモデルから得られた知識は，GnRH/ 性腺刺激ホルモンパルスを刺激して，家畜の繁殖能力を向上させる新規繁殖促進剤開発に寄与すると期待できる． kn-abstract=　Strategies for increasing reproductive performance are needed for domestic animals because for example the conception (pregnancy) rate has decreased in dairy cows around the world. Reproductive function is controlled by hormones released by the hypothalamus-pituitary-gonadal axis in mammals, including domestic animals. Of those hormones, tonic (pulsatile) gonadotropin-releasing hormone (GnRH) release is fundamentally important for gonadotropin release and gonadal activity. Therefore, uncovering the mechanism controlling GnRH pulses, that is GnRH pulse generator, is essential to improve reproductive technologies for domestic animals. The present review is focused on the indispensable role of arcuate nucleus (ARC) kisspeptin neurons (also known as KNDy neurons) as the GnRH pulse generator in mammals. First, we give a brief overview of studies on hypothalamic kisspeptin neurons throughout the past two decades. Second, we review studies that have provided direct evidence that ARC kisspeptin neurons serve as the GnRH pulse generator, with a special focus on our gene-modified rat models. Finally, we discuss the mechanism underlying GnRH pulse generation. The knowledge obtained from gene-modified rat models should be clinically important and could be adapted to new tools to improve reproductive performance in livestock by stimulating GnRH/gonadotropin pulses. en-copyright= kn-copyright= en-aut-name=NagaeMayuko en-aut-sei=Nagae en-aut-mei=Mayuko kn-aut-name=長江麻佑子 kn-aut-sei=長江 kn-aut-mei=麻佑子 aut-affil-num=1 ORCID= en-aut-name=UenoyamaYoshihisa en-aut-sei=Uenoyama en-aut-mei=Yoshihisa kn-aut-name=上野山賀久 kn-aut-sei=上野山 kn-aut-mei=賀久 aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil=岡山大学大学院環境生命自然科学研究科 affil-num=2 en-affil=Graduate School of Bioagricultural Sciences, Nagoya University kn-affil=名古屋大学大学院生命農学研究科 en-keyword=gene-modified rats kn-keyword=gene-modified rats en-keyword=GnRH kn-keyword=GnRH en-keyword=kisspeptin kn-keyword=kisspeptin en-keyword=LH kn-keyword=LH en-keyword=pulse generator kn-keyword=pulse generator END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=38 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exacerbation of diabetes due to F. Nucleatum LPS-induced SGLT2 overexpression in the renal proximal tubular epithelial cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Diabetes treatments by the control of sodium-glucose cotransporter 2 (SGLT2) is commonly conducted while there are still uncertainties about the mechanisms for the SGLT2 overexpression in kidneys with diabetes. Previously, we have reported that glomeruli and proximal tubules with diabetic nephropathy express toll-like receptor TLR2/4, and that the TLR ligand lipopolysaccharide (LPS) of periodontal pathogens have caused nephropathy in diabetic model mice. Recently, many researchers suggested that the periodontal pathogenic bacteria Fusobacterium (F.) nucleatum has the TLR4-associated strong activator of the colorectal inflammation and cancer. The present study aimed to investigate the possibility of F. nucleatum as an exacerbation factor of diabetes through the renal SGLT2 induction.
Methods The induction of the SGLT2 by F. nucleatum LPS (Fn-LPS) were investigated in the streptozotocin-induced diabetic mouse renal tissue and cultured renal proximal epithelial cells. The changes of blood glucose levels and survival curves in diabetic mice with Fn-LPS were analyzed. The Fn-LPS-induced SGLT2 production in the diabetic mouse renal tissue and in the cultured proximal epithelial cells was examined by ELISA, quantitative RT-PCR, and immunohistochemical analysis.
Results The SGLT2 expression in the cultured mouse tubular epithelial cells was significantly increased by TNF- or co-culture with Fn-LPS-supplemented J774.1 cells. The period to reach diabetic condition was significantly shorter in Fn-LPS-administered diabetic mice than in diabetic mice. All Fn-LPS-administered-diabetic mice reached humane endpoints during the healthy period of all of the mice administered Fn-LPS only. The promotion of the SGLT2 expression at the inner lumen of proximal tubules were stronger in the Fn-LPS-administered-diabetic mice than in diabetic mice. The renal tissue SGLT2 mRNA amounts and the number of renal proximal tubules with overexpressed SGLT2 in the lumen were more in the Fn-LPS-administered-diabetic mice than in diabetic mice.
Conclusions This study suggests that F. nucleatum causes the promotion of diabetes through the overexpression of SGLT2 in proximal tubules under the diabetic condition. Periodontitis with F. nucleatum may be a diabetic exacerbating factor. en-copyright= kn-copyright= en-aut-name=SekiAiko en-aut-sei=Seki en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KajiwaraKoichiro en-aut-sei=Kajiwara en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TeramachiJumpei en-aut-sei=Teramachi en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EgusaMasahiko en-aut-sei=Egusa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=SawaYoshihiko en-aut-sei=Sawa en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Oral Growth & Development, Fukuoka Dental College kn-affil= affil-num=3 en-affil=Department of Oral Function & Anatomy, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Dental Anesthesiology & Special Care Dentistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Dental Anesthesiology & Special Care Dentistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Oral Function & Anatomy, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=F. Nucleatum kn-keyword=F. Nucleatum en-keyword=Diabetic exacerbation kn-keyword=Diabetic exacerbation en-keyword=Diabetic nephropathy kn-keyword=Diabetic nephropathy en-keyword=SGLT2 kn-keyword=SGLT2 END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=3267 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and alpha-smooth muscle (alpha-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro. Anti-tumor effects of anti-IL-6R Ab on PM of GC were investigated in an orthotopic murine PM model. IL-6 expression was significantly correlated with alpha-SMA expression in clinical samples of GC, and higher IL-6 expression in the primary tumor was associated with poor prognosis of GC. Higher IL-6 and alpha-SMA expressions were also observed in PM of GC. In vitro, differentiation of fibroblasts into CAFs and chemoresistance were observed in GC cells cocultured with fibroblasts. Anti-IL-6R Ab inhibited the progression of PM in GC cells cocultured with fibroblasts in the orthotopic mouse model but could not inhibit the progression of PM consisting of GC cells alone. IL-6 expression in the TME was associated with poor prognosis of GC, and CAFs were associated with establishment and progression of PM via IL-6. Anti-IL-6R Ab could inhibit PM of GC by the blockade of IL-6 secreted by CAFs, which suggests its therapeutic potential for PM of GC. en-copyright= kn-copyright= en-aut-name=MitsuiEma en-aut-sei=Mitsui en-aut-mei=Ema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkuraTomohiro en-aut-sei=Okura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UneYuta en-aut-sei=Une en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhtsukaJunko en-aut-sei=Ohtsuka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhkiRieko en-aut-sei=Ohki en-aut-mei=Rieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=12 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Peritoneal metastasis kn-keyword=Peritoneal metastasis en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=Interleukin-6 kn-keyword=Interleukin-6 en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Interleukin-6 receptor antibody kn-keyword=Interleukin-6 receptor antibody END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=2486 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nomogram models for predicting outcomes in thyroid cancer patients with distant metastasis receiving 131iodine therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to establish and validate prognostic nomogram models for patients who underwent I-131 therapy for thyroid cancer with distant metastases. The cohort was divided into training (70%) and validation (30%) sets for nomogram development. Univariate and multivariate Cox regression analyses were used to identify independent predictors for overall survival (OS) and progression-free survival (PFS). Nomograms were developed based on these predictors, and Kaplan-Meier curves were constructed for validation. Among 451 patients who were screened, 412 met the inclusion criteria and were followed-up for a median duration of 65.2 months. The training and validation sets included 288 and 124 patients, respectively. Pathological type, first I-131 administrated activity, and lesion I-131 uptake in lesions were independent predictors for PFS. For OS, predictors included gender, age, metastasis site, first I-131 administrated activity, I-131 uptake, pulmonary lesion size, and stimulated thyroglobulin levels. These predictors were used to construct nomograms for predicting PFS and OS. Low-risk patients had significantly longer PFS and OS compared to high-risk patients, with 10-year PFS rates of 81.1% vs. 51.9% and 10-year OS rates of 86.2% vs. 37.4%. These may aid individualized prognostic assessment and clinical decision-making, especially in determining the prescribed activity for the first I-131 treatment. en-copyright= kn-copyright= en-aut-name=JinShui en-aut-sei=Jin en-aut-mei=Shui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YeXuemei en-aut-sei=Ye en-aut-mei=Xuemei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YeTing en-aut-sei=Ye en-aut-mei=Ting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChenXinyu en-aut-sei=Chen en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=JiJianfeng en-aut-sei=Ji en-aut-mei=Jianfeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WangJinyu en-aut-sei=Wang en-aut-mei=Jinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhuXin en-aut-sei=Zhu en-aut-mei=Xin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaoXiaochun en-aut-sei=Mao en-aut-mei=Xiaochun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YiHeqing en-aut-sei=Yi en-aut-mei=Heqing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Nuclear Medicine, Zhejiang Cancer Hospital kn-affil= affil-num=2 en-affil=Department of Nuclear Medicine, Zhejiang Cancer Hospital kn-affil= affil-num=3 en-affil=Department of Nuclear Medicine, Zhejiang Cancer Hospital kn-affil= affil-num=4 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=5 en-affil=Department of Nuclear Medicine, Zhejiang Cancer Hospital kn-affil= affil-num=6 en-affil=Medical records and statistics office, Zhejiang Cancer Hospital kn-affil= affil-num=7 en-affil=Key Laboratory of Head and Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital kn-affil= affil-num=8 en-affil=Department of Thyroid Surgery, Zhejiang Cancer Hospital kn-affil= affil-num=9 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Nuclear Medicine, Zhejiang Cancer Hospital kn-affil= en-keyword=131iodine kn-keyword=131iodine en-keyword=Activity kn-keyword=Activity en-keyword=Distant metastasis kn-keyword=Distant metastasis en-keyword=Iodine radioisotopes kn-keyword=Iodine radioisotopes en-keyword=Thyroid cancer kn-keyword=Thyroid cancer END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=46 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250113 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mapping Surface Potential in DNA Aptamer-Neurochemical and Membrane-Ion Interactions on the SOS Substrate Using Terahertz Microscopy en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we utilized a terahertz chemical microscope (TCM) to map surface potential changes induced by molecular interactions on silicon-on-sapphire (SOS) substrates. By functionalizing the SOS substrate with DNA aptamers and an ion-selective membrane, we successfully detected and visualized aptamer-neurochemical complexes through the terahertz amplitude. Additionally, comparative studies of DNA aptamers in PBS buffer and artificial cerebrospinal fluid (aCSF) were performed by computational structure modeling and terahertz measurements. Beyond neurochemicals, we also investigated calcium ions, measuring their concentrations in PDMS-fabricated micro-wells using minimal sample volumes. Our results highlight the capability of TCM as a powerful, label-free, and sensitive platform for the probing and mapping of surface potential arising from molecular interactions, with broad implications for biomedical diagnostics and research. en-copyright= kn-copyright= en-aut-name=MoritaKosei en-aut-sei=Morita en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitsudaYuta en-aut-sei=Mitsuda en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaSota en-aut-sei=Yoshida en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KiwaToshihiko en-aut-sei=Kiwa en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangJin en-aut-sei=Wang en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=terahertz chemical microscope kn-keyword=terahertz chemical microscope en-keyword=surface potential kn-keyword=surface potential en-keyword=DNA aptamer-neurochemical complexes kn-keyword=DNA aptamer-neurochemical complexes en-keyword=membrane-ion interactions kn-keyword=membrane-ion interactions en-keyword=SOS substrate kn-keyword=SOS substrate en-keyword=artificial cerebrospinal fluid kn-keyword=artificial cerebrospinal fluid END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=2 article-no= start-page=835 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pathophysiology of Group 3 Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary hypertension associated with lung diseases and/or hypoxia is classified as group 3 in the clinical classification of pulmonary hypertension. The efficacy of existing selective pulmonary vasodilators for group 3 pulmonary hypertension is still unknown, and it is currently associated with a poor prognosis. The mechanisms by which pulmonary hypertension occurs include hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, a decrease in pulmonary vascular beds, endothelial dysfunction, endothelial-to-mesenchymal transition, mitochondrial dysfunction, oxidative stress, hypoxia-inducible factors (HIFs), inflammation, microRNA, and genetic predisposition. Among these, hypoxic pulmonary vasoconstriction and subsequent pulmonary vascular remodeling are characteristic factors involving the pulmonary vasculature and are the focus of this review. Several factors have been reported to mediate vascular remodeling induced by hypoxic pulmonary vasoconstriction, such as HIF-1 alpha and mechanosensors, including TRP channels. New therapies that target novel molecules, such as mechanoreceptors, to inhibit vascular remodeling are awaited. en-copyright= kn-copyright= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TayaSatoshi en-aut-sei=Taya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurodaKazuhiro en-aut-sei=Kuroda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakayamaRie en-aut-sei=Nakayama en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pharmacy, Kinjo Gakuin University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=group 3 pulmonary hypertension kn-keyword=group 3 pulmonary hypertension en-keyword=hypoxic pulmonary vasoconstriction kn-keyword=hypoxic pulmonary vasoconstriction en-keyword=pulmonary vascular remodeling kn-keyword=pulmonary vascular remodeling END start-ver=1.4 cd-journal=joma no-vol=234 cd-vols= no-issue= article-no= start-page=120015 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reversible chemical modifications of graphene oxide for enhanced viral capture and release in water en-subtitle= kn-subtitle= en-abstract= kn-abstract=Detecting low concentrations of viruses in sewage water is crucial for monitoring the spread of emerging viral diseases. However, current detection methods, which involve concentrating viruses using traditional materials such as gauze or cotton, have limitations in effectively accomplishing this task. This study demonstrates that graphene oxide (GO), a two-dimensional carbon material, possesses strong viral adsorption capabilities. However, it lacks efficiency for effective viral release. Therefore, we designed a series of new GO-based materials, which exhibited a viral adsorption similar to pristine GO, while significantly enhancing their release performance by attaching alkyl chains and hydrophilic functional groups. Among the synthesized materials, 1,8-aminooctanol grafted to GO (GO-NH2C8OH) has emerged as the most promising candidate, achieving a viral release rate higher than 50 %. This superior performance can be attributed to the synergistic effect of the alkyl chain and the terminal OH group, which enhances both its affinity for viruses and water dispersibility. Furthermore, we have successfully applied GO-NH2C8OH in a new protocol for concentrating viruses from sewage wastewater. This approach has demonstrated a 200-fold increase in virus concentration, allowing PCR detection of this type of pathogens present in wastewater below the detection limit by direct analysis, underscoring its significant potential for virus surveillance. en-copyright= kn-copyright= en-aut-name=Ferr?-PujolPilar en-aut-sei=Ferr?-Pujol en-aut-mei=Pilar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObataSeiji en-aut-sei=Obata en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RayaJ?sus en-aut-sei=Raya en-aut-mei=J?sus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BiancoAlberto en-aut-sei=Bianco en-aut-mei=Alberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaHiroyuki en-aut-sei=Katayama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoTakashi en-aut-sei=Kato en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Institut de Chimie, UMR 7177 CNRS, Universit? de Strasbourg kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Urban Engineering, School of Engineering, The University of Tokyo kn-affil= affil-num=6 en-affil=Research Center for Water Environment Technology, School of Engineering, The University of Tokyo kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=Carbon nanomaterials kn-keyword=Carbon nanomaterials en-keyword=Functionalization kn-keyword=Functionalization en-keyword=Adsorption kn-keyword=Adsorption en-keyword=Desorption kn-keyword=Desorption en-keyword=Pathogens kn-keyword=Pathogens END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=4055-24 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=Dyspnea with Hemidiaphragm Elevation in a Patient with Giant Cell Arteritis: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=We herein report the first case of dyspnea with hemidiaphragm elevation in a 68-year-old woman with active giant cell arteritis (GCA), including successful treatment. Contrast-enhanced computed tomography showed a reduced density of the left ophthalmic artery and the left superficial temporal artery with increased soft tissue compared to the other side, indicating that the GCA had flared up and suggesting that the hemidiaphragm elevation might be caused by vasculitis-associated ischemia of the right phrenic nerve. Hemidiaphragm paralysis due to vasculitis-associated ischemia in patients with GCA needs to be distinguished from local infection, tumors, and hepatomegaly, which are the major causes of hemidiaphragm elevation. en-copyright= kn-copyright= en-aut-name=AsanoYosuke en-aut-sei=Asano en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KubotaNatsuki en-aut-sei=Kubota en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TerajimaYuya en-aut-sei=Terajima en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoKazuya en-aut-sei=Matsumoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShidaharaKenta en-aut-sei=Shidahara en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiroseKei en-aut-sei=Hirose en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakadoiTakato en-aut-sei=Nakadoi en-aut-mei=Takato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NawachiShoichi en-aut-sei=Nawachi en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatayamaYu en-aut-sei=Katayama en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Takano-NarazakiMariko en-aut-sei=Takano-Narazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SadaKen-Ei en-aut-sei=Sada en-aut-mei=Ken-Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=giant cell arteritis kn-keyword=giant cell arteritis en-keyword=dyspnea kn-keyword=dyspnea en-keyword=hemidiaphragm elevation kn-keyword=hemidiaphragm elevation en-keyword=phrenic nerve paralysis kn-keyword=phrenic nerve paralysis en-keyword=FDG-PET kn-keyword=FDG-PET en-keyword=case report kn-keyword=case report END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=4 article-no= start-page=2679 end-page=2687 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Formation of Nanowindow between Graphene Oxide and Carbon Nanohorn Assisted by Metal Ions en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study presents a novel nanostructured material formed by inserting oxidized carbon nanohorns (CNHox) between layered graphene oxide (GO) nanosheets using metal ions (M) from nitrate as intermediates. The resulting GO?CNHox-M structure effectively mitigated interlayer aggregation of the GO nanosheets. This insertion strategy promoted the formation of nanowindows on the surface of the GO sheets and larger mesopores between the GO nanosheets, improving material porosity. Characterization revealed successful CNHox insertion, which increased interlayer spacing and reduced GO stacking. The GO?CNHox-Ca exhibited a significantly higher specific surface area (SSA) and pore volume than pure GO, with values of 374 m2 g?1 and 0.36 mL g?1, respectively. The GO?CNHox-K composite also exhibited a well-developed pore structure with an SSA of 271 m2 g?1 and pore volume of 0.26 mL g?1. These findings demonstrate that Ca2+ or K+ ions effectively link GO and CNHox, validating the success of this insertion approach in reducing GO aggregation. Metal ions played a crucial role in the insertion process by facilitating electrostatic interactions and coordination bonds between GO and CNHox. This study provides new insights into reducing GO agglomeration and expanding the application of GO-based materials. en-copyright= kn-copyright= en-aut-name=LiZhao en-aut-sei=Li en-aut-mei=Zhao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToyotaMoeto en-aut-sei=Toyota en-aut-mei=Moeto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhkuboTakahiro en-aut-sei=Ohkubo en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=361 cd-vols= no-issue= article-no= start-page=114657 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=Crosstalk between prolactin, insulin-like growth factors, and thyroid hormones in feather growth regulation in neonatal chick wings en-subtitle= kn-subtitle= en-abstract= kn-abstract=The elongation of primary feathers in neonatal chicks is delayed by the late-feathering K gene located on the Z chromosome. We recently found that the K gene slows feather growth by reducing the number of functional prolactin (PRL) receptor (PRLR) dimers. In this study, we investigated the molecular mechanisms by which PRL promotes feather elongation. RT-qPCR and immunohistochemistry analyses revealed that PRLRs are predominantly localized in the pulp rather than in the epidermal layer of the feather follicle. Treatment of primary cultured feather pulp cells with PRL increased the expression of mRNAs for insulin-like growth factors (IGFs; IGF-1 and IGF-2) and type 2 deiodinase (DIO2). Furthermore, treatments with IGF-1 and triiodothyronine (T3) reciprocally enhanced the expression of mRNAs for DIO2 and IGFs. Additionally, BrdU staining in neonatal chicks showed that T3 promoted cell proliferation in both the epidermal layer and pulp cells, while this effect was suppressed by an IGF-1 receptor (IGF1R) inhibitor. These findings suggest a novel model in which PRL upregulates IGFs and DIO2 in feather pulp cells, creating a positive feedback loop between IGFs and T3, ultimately leading to the promotion of cell proliferation in both the epidermal layer and the pulp cells by IGFs. This is the first report proposing crosstalk between PRL, thyroid hormone (TH), and IGFs in feather follicles. en-copyright= kn-copyright= en-aut-name=NozawaYuri en-aut-sei=Nozawa en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkamuraAyako en-aut-sei=Okamura en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuchiHibiki en-aut-sei=Fukuchi en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinoharaMasamichi en-aut-sei=Shinohara en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Prolactin kn-keyword=Prolactin en-keyword=Thyroid hormone kn-keyword=Thyroid hormone en-keyword=IGF kn-keyword=IGF en-keyword=Iodothyronine deiodinase kn-keyword=Iodothyronine deiodinase en-keyword=Feather growth kn-keyword=Feather growth END start-ver=1.4 cd-journal=joma no-vol=941 cd-vols= no-issue= article-no= start-page=149244 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250315 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of pennaceous barbule cell factor (PBCF), a novel gene with spatiotemporal expression in barbule cells during feather development en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bird contour feathers exhibit a complex hierarchical structure composed of a rachis, barbs, and barbules, with barbules playing a crucial role in maintaining feather structure and function. Understanding the molecular mechanisms underlying barbule formation is essential for advancing our knowledge of avian biology and evolution. In this study, we identified a novel gene, pennaceous barbule cell factor (PBCF), using microarray analysis, RT-PCR, and in situ hybridization. PBCF is expressed in barbule cells adjacent to the ramus during pennaceous barbule formation, where these cells fuse with the ramus to establish the feather’s branching structure. PBCF expression occurs transiently after melanin pigmentation of the barbule plates but before the expression of barbule-specific keratin 1 (BlSK1). Orthologues of PBCF, predicted to be secreted proteins, are conserved across avian species, with potential homologues detected in reptiles, suggesting an evolutionary lineage-specific adaptation. Additionally, PBCF is expressed in non-vacuolated notochord cells and the extra-embryonic ectoderm of the yolk sac, hinting at its broader developmental significance. The PBCF gene produces two mRNA isoforms via alternative splicing, encoding a secreted protein and a glycophosphatidylinositol (GPI)-anchored membrane-bound protein, indicating functional versatility. These findings suggest that PBCF may be involved as an avian-specific extracellular matrix component in cell adhesion and/or communication, potentially contributing to both feather development and embryogenesis. Further investigation of PBCF’s role in feather evolution and its potential functions in other vertebrates could provide new insights into the interplay between development and evolution. en-copyright= kn-copyright= en-aut-name=NakaokaMinori en-aut-sei=Nakaoka en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuchiHibiki en-aut-sei=Fukuchi en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OgoshiMaho en-aut-sei=Ogoshi en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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 Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Feather kn-keyword=Feather en-keyword=Barbule kn-keyword=Barbule en-keyword=Branching kn-keyword=Branching en-keyword=Chicken kn-keyword=Chicken en-keyword=Yolk sac membrane kn-keyword=Yolk sac membrane en-keyword=Notochord kn-keyword=Notochord END start-ver=1.4 cd-journal=joma no-vol=145 cd-vols= no-issue=1 article-no= start-page=7 end-page=14 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Precision Medicine for Patients with Renal Cell Carcinoma Based on Drug-metabolizing Enzyme Expression Levels kn-title=薬物代謝酵素の発現情報を活用した腎がん治療の個別適正化 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Notable advances have recently been achieved in drug therapies for renal cell carcinoma (RCC). Several tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have been approved for metastatic RCC (mRCC). The current first-line treatment for mRCC involves combination therapies using TKIs and ICIs. However, there is no consensus on which TKI+ICI therapy is best or how to select the appropriate therapy for individual patients with RCC. The kidney expresses various metabolic enzymes, including CYP and uridine diphosphate glucose (UDP)-glucuronosyltransferase (UGT). Although information on CYP and UGT expression in the kidney is limited compared to our understanding of liver expression, the main CYP and UGT subtypes expressed at high levels in the kidney are estimated to be CYP2B6, CYP3A5, CYP4A11, CYP4F2, UGT1A6, UGT1A9, and UGT2B7. In RCC, the expression profiles and levels of these enzymes are somewhat altered compared with normal kidney. The main known subtypes of CYP and UGT in RCC are CYP1B1, CYP3A5, CYP4A11, UGT1A6, UGT1A9, UGT1A10, and UGT2B7. High CYP expression has been reported in several cancers, possibly conferring resistance to anti-cancer drugs including TKIs, due to extensive drug metabolism. Additionally, CYP and UGT expression levels may possibly affect cancer prognosis by metabolizing endogenous substrates, regardless of their role in anti-cancer drug metabolism. In this review, I discuss CYP and UGT expression level profiles in RCC based on previously published papers, including ours, and examine possible relationships between these enzyme expression profiles and treatment outcomes for patients with RCC. en-copyright= kn-copyright= en-aut-name=MatsumotoJun en-aut-sei=Matsumoto en-aut-mei=Jun kn-aut-name=松本准 kn-aut-sei=松本 kn-aut-mei=准 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域（薬学系）疾患薬理制御科学分野 en-keyword=renal cell carcinoma (RCC) kn-keyword=renal cell carcinoma (RCC) en-keyword=kidney kn-keyword=kidney en-keyword=CYP kn-keyword=CYP en-keyword=uridine diphosphate glucose (UDP)-glucuronosyltransferase kn-keyword=uridine diphosphate glucose (UDP)-glucuronosyltransferase en-keyword=metabolism kn-keyword=metabolism END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=1 article-no= start-page=4 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract=To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration. The knockdown of Ndfip1 expression with Ndfip1 siRNA significantly aggravated METH-induced neurotoxicity in the cultured monoaminergic neuronal cells. These results suggest that drastic increases in Ndfip1 mRNA is compensatory reaction to protect neurons against METH-induced neurotoxicity. en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CadetJean Lud en-aut-sei=Cadet en-aut-mei=Jean Lud kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=Molecular Neuropsychiatry Section, Intramural Research Program, NIH/ NIDA kn-affil= en-keyword=Methamphetamine kn-keyword=Methamphetamine en-keyword=Neurotoxicity kn-keyword=Neurotoxicity en-keyword=Nedd4 kn-keyword=Nedd4 en-keyword=Ndfip1 kn-keyword=Ndfip1 en-keyword=Differential display kn-keyword=Differential display END start-ver=1.4 cd-journal=joma no-vol=741 cd-vols= no-issue= article-no= start-page=151006 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=S-adenosylmethionine and S-adenosyl-L-homocysteine metabolism is involved in the sperm motility and in vitro fertility rate in mouse en-subtitle= kn-subtitle= en-abstract= kn-abstract=Increased fragmentation of sperm DNA has been implicated in male infertility. Folate deficiency results in impaired methionine synthesis, depletion of S-adenosylmethionine (SAM) levels, an increase in S-adenosyl-l-homocysteine (SAH) levels, and increased DNA fragmentation. Disruption of the dynamic balance between SAM and SAH may also contribute, although the details of this process are not yet fully understood. We investigated the localization of SAM, SAH, and S-adenosylhomocysteine hydrolase (SAHH), and whether SAM/SAH metabolism contributes to sperm motility and fertilization rate. SAM, SAH, and SAHH levels were assessed in the acrosome, midpiece, and tail of spermatozoa. Chemical inhibition of SAM/SAH metabolism and extracellular SAH significantly decreased the straight-line velocity (VSL), curvilinear velocity (VCL), and amplitude lateral head displacement (ALH) of sperm cells, which were thus unable to swim forward and perform oscillatory movements in place. This significantly reduced the fertilization rate. Therefore, the disruption of the SAM/SAH balance may contribute to male infertility. en-copyright= kn-copyright= en-aut-name=KawaiTomoko en-aut-sei=Kawai en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= affil-num=1 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=SAM/SAH metabolism kn-keyword=SAM/SAH metabolism en-keyword=Sperm motility kn-keyword=Sperm motility en-keyword=Fertilization rate kn-keyword=Fertilization rate END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=4 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Maternal smoking during infancy increases the risk of allergic diseases in children: a nationwide longitudinal survey in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The incidence of allergic diseases has been increasing in Japan. In particular, a serious decline in the age of onset of allergic rhinitis has been observed. Passive smoking from parental smoking has a significant impact on children’s health; however, it is difficult to restrict smoking in the home. While various studies have previously reported on the relationship between passive smoking and the development of allergic diseases in children. However, there have been no reports on passive smoking and allergic diseases on a national scale.
Methods Using Japanese national longitudinal survey data (n?=?38,444) for newborns born between May 10 and 24, 2010, we assessed parental smoking habits when their children were 6 months old and investigated the association with the development of allergic diseases until the age of 5.5 years. The risk ratios and 95% confidence intervals for the development of different allergic diseases were analyzed after adjusting for potential confounders using Poisson regression with a robust error variance.
Results The risk ratio for developing allergic rhinitis/allergic conjunctivitis (AR/AC) in children was significantly higher in the maternal smoking groups (?≦?10 cigarettes/day; RR 1.15, 95% CI 1.02?1.30; ≧11 cigarettes/day; RR 1.16, 95% CI 0.93?1.44). Furthermore, associations were found between the maternal smoking group in the presence of paternal smoking and the risk of developing bronchial asthma (?≦?10, RR 1.33 95% CI 1.17?1.52; ≧11, RR 1.71 95% CI 1.38?2.1), food allergy (?≦?10, RR 1.36 95% CI 1.12?1.63; ≧11, RR 1.25 95% CI 0.84?1.86), atopic dermatitis (?≦?10, RR 1.42 95% CI 1.22?1.66; ≧11, RR 1.6 95% CI 1.2?2.13), and AR/AC (?≦?10, RR 1.21 95% CI 1.07?1.36; ≧11, RR 1.35 95% CI 1.09?1.67).
Conclusions Maternal smoking during infancy increases the risk of developing AR/AC in children. Considering paternal smoking, maternal smoking further increased the risk of developing allergic diseases in children, suggesting that reducing parental smoking at home may reduce the risk of developing allergic diseases in children. en-copyright= kn-copyright= en-aut-name=ShigeharaKenji en-aut-sei=Shigehara en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UdaKazuhiro en-aut-sei=Uda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoYukie en-aut-sei=Saito en-aut-mei=Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pediatrics, 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 Pediatric Acute Diseases, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Allergic rhinitis kn-keyword=Allergic rhinitis en-keyword=Bronchial asthma kn-keyword=Bronchial asthma en-keyword=Atopic dermatitis kn-keyword=Atopic dermatitis en-keyword=National cohort study kn-keyword=National cohort study en-keyword=Passive smoking kn-keyword=Passive smoking END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue= article-no= start-page=106672 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=Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways en-subtitle= kn-subtitle= en-abstract= kn-abstract=Resveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25-50 mu M, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation. en-copyright= kn-copyright= en-aut-name=OkamotoSaki en-aut-sei=Okamoto en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KakimaruSaya en-aut-sei=Kakimaru en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoreishiMayuko en-aut-sei=Koreishi en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoMika en-aut-sei=Sakamoto en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoHideya en-aut-sei=Ando en-aut-mei=Hideya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujinoYoshio en-aut-sei=Tsujino en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=National Institute of Genetics, ROIS kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Applied Chemistry and Biotechnology, Okayama University of Science kn-affil= affil-num=7 en-affil=Graduate School of Science, Technology, and Innovation, Kobe University kn-affil= affil-num=8 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Antioxidant kn-keyword=Antioxidant en-keyword=Lysosomes kn-keyword=Lysosomes en-keyword=Autophagy kn-keyword=Autophagy en-keyword=Resveratrol kn-keyword=Resveratrol en-keyword=Skin fibroblasts kn-keyword=Skin fibroblasts en-keyword=Bioactive compounds kn-keyword=Bioactive compounds END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=2577 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plasma S100A8/A9 level predicts response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Blood-based predictive markers for the efficacy of immune checkpoint inhibitors (ICIs) have not yet been established. We investigated the association of the plasma level of S100A8/A9 with the efficacy of immunotherapy. We evaluated patients with unresectable stage III/IV or recurrent non-small cell lung cancer (NSCLC) who were treated with ICIs at Okayama University Hospital. The pre-treatment plasma levels of S100A8/A9 were analyzed. Eighty-one eligible patients were included (median age, 69 years). Sixty-two patients were men, 54 had adenocarcinoma, 74 had performance status (PS) 0?1, and 47 received ICIs as first-line treatment. The median time to treatment failure (TTF) for ICIs was 5.7 months, and the median overall survival (OS) was 19.6 months. The TTF and OS were worse in patients with high plasma S100A8/A9 levels (??2.475 ?g/mL) (median TTF: 4.3 vs. 8.5 months, p?=?0.009; median OS: 15.4 vs. 38.0 months, p?=?0.001). Multivariate analysis revealed that PS???2, liver metastasis, and high plasma S100A8/A9 levels were significantly associated with short TTF and OS. In conclusion, plasma S100A8/A9 level may have a limited effect on ICI therapy for NSCLC. en-copyright= kn-copyright= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 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=13 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=S100A8/A9 kn-keyword=S100A8/A9 en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=21 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Gut-Kidney Axis in Chronic Kidney Diseases en-subtitle= kn-subtitle= en-abstract= kn-abstract=The gut-kidney axis represents the complex interactions between the gut microbiota and kidney, which significantly impact the progression of chronic kidney disease (CKD) and overall patient health. In CKD patients, imbalances in the gut microbiota promote the production of uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which impair renal function and contribute to systemic inflammation. Mechanisms like endotoxemia, immune activation and oxidative stress worsen renal damage by activating pro-inflammatory and oxidative pathways. Insights into these mechanisms highlight the impact of gut-derived metabolites, bacterial translocation, and immune response changes on kidney health, suggesting new potential approaches for CKD treatment. Clinical applications, such as dietary interventions, prebiotics, probiotics and fecal microbiota transplantation, are promising in adjusting the gut microbiota to alleviate CKD symptoms and slow disease progression. Current research highlights the clinical relevance of the gut-kidney axis, but further study is essential to clarify these mechanisms' diagnostic biomarkers and optimize therapeutic interventions. This review emphasizes the importance of an integrated approach to CKD management, focusing on the gut microbiota as a therapeutic target to limit kidney injury. en-copyright= kn-copyright= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=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, 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=gut-kidney axis kn-keyword=gut-kidney axis en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=uremic toxin kn-keyword=uremic toxin en-keyword=dysbiosis kn-keyword=dysbiosis en-keyword=gut microbiota kn-keyword=gut microbiota END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=60 end-page= 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=Novel Drug Delivery Particles Can Provide Dual Effects on Cancer "Theranostics" in Boron Neutron Capture Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction 10B (n, alpha) 7Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, “AB-type” Lactosome? nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely o-Carborane (Carb) or 1,2-dihexyl-o-Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the “molecular glue” effect. Here we present in vivo and ex vivo studies with human pancreatic cancer (AsPC-1) cells to find therapeutically optimal formulas and the appropriate treatment conditions for these particles. The biodistribution of the particles was assessed by the tumor/normal tissue ratio (T/N) in terms of tumor/muscle (T/M) and tumor/blood (T/B) ratios using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG). The in vivo and ex vivo accumulation of B delivered by the injected AB-Lac particles in tumor lesions reached a maximum by 12 h post-injection. Irradiation studies conducted both in vitro and in vivo showed that AB-Lac particles-loaded with either 10B-Carb or 10B-diC6-Carb significantly inhibited the growth of AsPC-1 cancer cells or strongly inhibited their growth, with the latter method being significantly more effective. Surprisingly, a similar in vitro and in vivo irradiation study showed that ICG-labeled AB-Lac particles alone, i.e., without any 10B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with 10B compound(s) may be a novel and promising candidate for providing not only NIRF imaging for a practical diagnosis but also the dual therapeutic effects of induced cancer cell death, i.e., “theranostics”. en-copyright= kn-copyright= en-aut-name=FithroniAbdul Basith en-aut-sei=Fithroni en-aut-mei=Abdul Basith kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueHaruki en-aut-sei=Inoue en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhouShengli en-aut-sei=Zhou en-aut-mei=Shengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HakimTaufik Fatwa Nur en-aut-sei=Hakim en-aut-mei=Taufik Fatwa Nur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TadaTakashi en-aut-sei=Tada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiMinoru en-aut-sei=Suzuki en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakuraiYoshinori en-aut-sei=Sakurai en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshimotoManabu en-aut-sei=Ishimoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamadaNaoyuki en-aut-sei=Yamada en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SauriasariRani en-aut-sei=Sauriasari en-aut-mei=Rani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SauerweinWolfgang A. G. en-aut-sei=Sauerwein en-aut-mei=Wolfgang A. G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=7 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=8 en-affil=J-BEAM, Inc. kn-affil= affil-num=9 en-affil=Nihon Fukushi Fuiin Holding, Co., Ltd. kn-affil= affil-num=10 en-affil=Faculty of Pharmacy, Universitas Indonesia kn-affil= affil-num=11 en-affil=Deutsche Gesellschaft f?r Bor-Neutroneneinfangtherapie DGBNCT e.V., University Hospital Essen, Klinik f?r Strahlentherapie kn-affil= affil-num=12 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=13 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=14 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=boron neutron capture therapy (BNCT) kn-keyword=boron neutron capture therapy (BNCT) en-keyword=dual therapeutic effects kn-keyword=dual therapeutic effects en-keyword=Lactosome ? kn-keyword=Lactosome ? en-keyword=hydrophobic boron compound kn-keyword=hydrophobic boron compound en-keyword=neutron irradiation kn-keyword=neutron irradiation en-keyword=theranostics kn-keyword=theranostics END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=2 article-no= start-page=80 end-page=90 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230627 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Antioxidant action of xanthine oxidase inhibitor febuxostat protects the liver and blood vasculature in SHRSP5/Dmcr rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Xanthine oxidase (XO) generates reactive oxygen species during uric acid production. Therefore, XO inhibitors, which suppress oxidative stress, may effectively treat non-alcoholic steatohepatitis (NASH) and atherosclerosis via uric acid reduction. In this study, we examined the antioxidant effect of the XO inhibitor febuxostat on NASH and atherosclerosis in stroke-prone spontaneously hypertensive 5 (SHRSP5/Dmcr) rats.
Methods: SHRSP5/Dmcr rats were divided into three groups: SHRSP5/Dmcr + high-fat and high-cholesterol (HFC) diet [control group, n = 5], SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) [fructose group, n = 5], and SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) + febuxostat (1.0 mg/kg/day) [febuxostat group, n = 5]. Glucose and insulin resistance, blood biochemistry, histopathological staining, endothelial function, and oxidative stress markers were evaluated.
Results: Febuxostat reduced the plasma uric acid levels. Oxidative stress-related genes were downregulated, whereas antioxidant factor-related genes were upregulated in the febuxostat group compared with those in the fructose group. Febuxostat also ameliorated inflammation, fibrosis, and lipid accumulation in the liver. Mesenteric lipid deposition decreased in the arteries, and aortic endothelial function improved in the febuxostat group.
Conclusions: Overall, the XO inhibitor febuxostat exerted protective effects against NASH and atherosclerosis in SHRSP5/Dmcr rats. en-copyright= kn-copyright= en-aut-name=KakimotoMai en-aut-sei=Kakimoto en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiMoe en-aut-sei=Fujii en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoIkumi en-aut-sei=Sato en-aut-mei=Ikumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HonmaKoki en-aut-sei=Honma en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakayamaHinako en-aut-sei=Nakayama en-aut-mei=Hinako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KiriharaSora en-aut-sei=Kirihara en-aut-mei=Sora kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukuokaTaketo en-aut-sei=Fukuoka en-aut-mei=Taketo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=RanShang en-aut-sei=Ran en-aut-mei=Shang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitamoriKazuya en-aut-sei=Kitamori en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoShusei en-aut-sei=Yamamoto en-aut-mei=Shusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeShogo en-aut-sei=Watanabe en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Okayama University, Graduate School of Health Sciences, Department of Medical Technology kn-affil= affil-num=2 en-affil=Okayama University, Graduate School of Health Sciences, Department of Medical Technology kn-affil= affil-num=3 en-affil=Okayama University, Graduate School of Health Sciences, Department of Medical Technology kn-affil= affil-num=4 en-affil=Okayama University, Graduate School of Health Sciences, Department of Medical Technology kn-affil= affil-num=5 en-affil=Okayama University, Graduate School of Health Sciences, Department of Medical Technology kn-affil= affil-num=6 en-affil=Okayama University, Graduate School of Health Sciences, Department of Medical Technology kn-affil= affil-num=7 en-affil=Okayama University, Faculty of Health Sciences, Department of Medical Technology kn-affil= affil-num=8 en-affil=Okayama University, Graduate School of Health Sciences, Department of Medical Technology kn-affil= affil-num=9 en-affil=Okayama University, Academic Field of Health Science kn-affil= affil-num=10 en-affil=Kinjo Gakuin University, College of Human Life and Environment kn-affil= affil-num=11 en-affil=Okayama University, Graduate School of Health Sciences, Department of Medical Technology kn-affil= affil-num=12 en-affil=Okayama University, Academic Field of Health Science kn-affil= en-keyword=Anti-inflammatory kn-keyword=Anti-inflammatory en-keyword=Atherosclerosis kn-keyword=Atherosclerosis en-keyword=Febuxostat kn-keyword=Febuxostat en-keyword=Non-alcoholic steatohepatitis (NASH) kn-keyword=Non-alcoholic steatohepatitis (NASH) en-keyword=Oxidative stress kn-keyword=Oxidative stress en-keyword=Uric acid kn-keyword=Uric acid END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=3 article-no= start-page=98 end-page=101 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230727 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of a Transwoman with Colorectal Cancer after Flap Vaginoplasty en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vaginoplasty is a gender-affirming surgery (GAS) for transwomen that laid its foundation in the 1950s and continues to be widely practiced worldwide. We present here a case of a 70-year-old transwoman who underwent lower anterior resection for rectal cancer 12 years after vaginoplasty. The preoperative diagnosis was rectal cancer (Rb-Ra, type 2, cT2N0M0, stage 1). All imaging studies showed a cord-like structure between the prostate and the anterior wall of the rectum, which was thought to be the neovagina. Careful dissection of the anterior rectal wall was required because the distance between the neovagina and the rectum was only 1.5 mm. The role of hormonal therapy and GAS in cancer development in transwomen is unclear. It is important to have regular check-ups for malignancies in patients who have undergone GAS, and if surgical procedures are needed, they should be treated by physicians who are familiar with the procedure. en-copyright= kn-copyright= en-aut-name=WatanabeShiho en-aut-sei=Watanabe en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujimotoSari en-aut-sei=Fujimoto en-aut-mei=Sari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeToshiyuki en-aut-sei=Watanabe en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakedaSho en-aut-sei=Takeda en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaritaShuhei en-aut-sei=Narita en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamashitaKoya en-aut-sei=Yamashita en-aut-mei=Koya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=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=NambaYuzaburo en-aut-sei=Namba en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KimataYoshihiro en-aut-sei=Kimata en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Minimally Invasive Therapy Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gender Center, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital kn-affil= en-keyword=vaginoplasty kn-keyword=vaginoplasty en-keyword=gender-affirming surgery kn-keyword=gender-affirming surgery en-keyword=transwomen kn-keyword=transwomen en-keyword=rectal cancer kn-keyword=rectal cancer END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=52 article-no= start-page=35202 end-page=35213 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bright Quantum-Grade Fluorescent Nanodiamonds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Optically accessible spin-active nanomaterials are promising as quantum nanosensors for probing biological samples. However, achieving bioimaging-level brightness and high-quality spin properties for these materials is challenging and hinders their application in quantum biosensing. Here, we demonstrate bright fluorescent nanodiamonds (NDs) containing 0.6?1.3-ppm negatively charged nitrogen-vacancy (NV) centers by spin-environment engineering via enriching spin-less 12C-carbon isotopes and reducing substitutional nitrogen spin impurities. The NDs, readily introduced into cultured cells, exhibited improved optically detected magnetic resonance (ODMR) spectra; peak splitting (E) was reduced by 2?3 MHz, and microwave excitation power required was 20 times lower to achieve a 3% ODMR contrast, comparable to that of conventional type-Ib NDs. They show average spin-relaxation times of T1 = 0.68 ms and T2 = 3.2 μs (1.6 ms and 5.4 μs maximum) that were 5- and 11-fold longer than those of type-Ib, respectively. Additionally, the extended T2 relaxation times of these NDs enable shot-noise-limited temperature measurements with a sensitivity of approximately 0.28K/√Hz. The combination of bulk-like NV spin properties and enhanced fluorescence significantly improves the sensitivity of ND-based quantum sensors for biological applications. en-copyright= kn-copyright= en-aut-name=OshimiKeisuke en-aut-sei=Oshimi en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiwataHitoshi en-aut-sei=Ishiwata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakashimaHiromu en-aut-sei=Nakashima en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Mandi?Sara en-aut-sei=Mandi? en-aut-mei=Sara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHina en-aut-sei=Kobayashi en-aut-mei=Hina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TeramotoMinori en-aut-sei=Teramoto en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujiHirokazu en-aut-sei=Tsuji en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishibayashiYoshiki en-aut-sei=Nishibayashi en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShikanoYutaka en-aut-sei=Shikano en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AnToshu en-aut-sei=An en-aut-mei=Toshu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraMasazumi en-aut-sei=Fujiwara en-aut-mei=Masazumi 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 Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=The National Institutes for Quantum Science and Technology (QST), Institute for Quantum Life Science (iQLS) kn-affil= affil-num=3 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=7 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=8 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=9 en-affil=Institute of Systems and Information Engineering, University of Tsukuba kn-affil= affil-num=10 en-affil=School of Materials Science, Japan Advanced Institute of Science and Technology kn-affil= affil-num=11 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= en-keyword=nanodiamonds kn-keyword=nanodiamonds en-keyword=nitrogen-vacancy centers kn-keyword=nitrogen-vacancy centers en-keyword=spins kn-keyword=spins en-keyword=spin-relaxation times kn-keyword=spin-relaxation times en-keyword=quantum biosensor kn-keyword=quantum biosensor en-keyword=cellular probes kn-keyword=cellular probes END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=74 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Case series showing the safety and changes in lipid profiles of hemodialysis patients with hypertriglyceridemia after pemafibrate administration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Cardiovascular disease is a major cause of morbidity and mortality in patients with chronic kidney disease and end-stage renal disease (ESRD). Dyslipidemia is a key focus of cardiovascular therapy and is characterized by hypertriglyceridemia mainly caused by lipoprotein lipase-mediated metabolism of ApoC-III in patients with ESRD. Pemafbrate, a selective peroxisome proliferator-activated receptor alpha modulator, can be used regardless of renal function and inhibit ApoC-III expression in the liver.
Case presentation We reported the cases of four patients on hemodialysis who met at least 175 mg/dL of triglycerides on the consecutive three tests between September 2022 and November 2022 and took 0.1 mg pemafbrate twice a day from November 2022 to May 2023. They experienced no adverse events after pemafbrate treatment. Pemafbrate signifcantly reduced triglyceride (TG) (302±72 to 140±50 mg/dL, p=0.048), total cholesterol (187±34 to 156±48 mg/dL, p=0.025), and Apo C-III (15.9±8.2 to 12.6±7.1, p=0.030) levels. Apo A-II levels signifcantly increased after treatment (27.0±6.1 to 37.1±5.8, p=0.041).
Conclusions Pemafbrate decreased TG, total cholesterol, and Apo-CIII and increased Apo A-II without adverse events. Further study is needed to examine the favorable efects of pemafbrate on the risk of CVD. en-copyright= kn-copyright= en-aut-name=OkadaRino en-aut-sei=Okada en-aut-mei=Rino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiNaoya en-aut-sei=Kobayashi en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiharaHiroyuki en-aut-sei=Ishihara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YokoyamaTomohisa en-aut-sei=Yokoyama en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MifuneTomoyo en-aut-sei=Mifune en-aut-mei=Tomoyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakurabuYoshimasa en-aut-sei=Sakurabu en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NojimaIchiro en-aut-sei=Nojima en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=4 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=5 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=6 en-affil=Okayama Saidaiji Hospital kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Hemodialysis kn-keyword=Hemodialysis en-keyword=Dyslipidemia kn-keyword=Dyslipidemia en-keyword=Apolipoprotein kn-keyword=Apolipoprotein en-keyword=Pemafibrate kn-keyword=Pemafibrate END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=e70071 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Undetermined Ruptured Low-Grade Appendiceal Mucinous Neoplasm Following High-Energy Blunt Abdominal Trauma Requiring Emergency Laparotomy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Blunt abdominal trauma causing intraperitoneal injury and/or bleeding can be life-threatening, requiring immediate intervention. Diagnosing these cases can be challenging, especially when pre-existing conditions are involved. Low-grade appendiceal mucinous neoplasm (LAMN) is a rare tumor of the appendix that can lead to pseudomyxoma peritonei. Herein, we present a case of ruptured LAMN following blunt abdominal trauma after a high-energy head-on collision, complicating the differentiation from other intraperitoneal injuries. A 42-year-old Japanese female was brought to our hospital following high-energy head-on collision. She presented with stable vital signs, complaining of anterior chest pain and abdominal tenderness without peritoneal irritation. Computed tomography scans indicated multiple fractures in her chest and complex fluid around the Douglas fossa extending to the ileocecal area, with a slightly dilated appendix tip. Despite stable vitals, emergency laparotomy was needed for suspected peritonitis and/or intraperitoneal hemorrhage. Emergency laparotomy revealed yellowish, jelly-like ascites and a ruptured appendiceal tumor. LAMN was suspected, and the appendix was completely resected, with cytoreductive surgery carefully performed. Histopathological examination confirmed the diagnosis of LAMN. Postoperative course was uneventful, and the patient was discharged on Day 13 and referred for further LAMN management. This case report highlights the diagnostic difficulties of LAMN rupture following blunt abdominal trauma, stressing the need to consider rare conditions like LAMN in differential diagnoses of acute abdomen posttrauma. en-copyright= kn-copyright= en-aut-name=MatsuoIppei en-aut-sei=Matsuo en-aut-mei=Ippei 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=TsujiAkari en-aut-sei=Tsuji en-aut-mei=Akari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanabeRyo en-aut-sei=Tanabe en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumuraToshihisa en-aut-sei=Matsumura en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimabaraMikoto en-aut-sei=Shimabara en-aut-mei=Mikoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=TakagiShoji en-aut-sei=Takagi en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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 Digestive Surgery, Japanese Red Cross Okayama Hospital kn-affil= affil-num=6 en-affil=Department of Digestive Surgery, Japanese Red Cross Okayama Hospital kn-affil= affil-num=7 en-affil=Department of Digestive Surgery, Japanese Red Cross Okayama Hospital kn-affil= affil-num=8 en-affil=Department of Digestive Surgery, Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=abdominal injuries kn-keyword=abdominal injuries en-keyword=appendiceal neoplasms kn-keyword=appendiceal neoplasms en-keyword=computed tomography kn-keyword=computed tomography en-keyword=mucinous kn-keyword=mucinous en-keyword=pseudomyxoma peritonei kn-keyword=pseudomyxoma peritonei END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=1 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predictive marker for response to trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Trifluridine/tipiracil (FTD/TPI) is one of the options for late-line treatment of colorectal cancer (CRC). However, the specific patient populations that would particularly benefit from it remain unclear. This study attempted to identify predictive markers of chemotherapy efficacy with trifluridine/tipiracil (FTD/TPI), focusing on the RNA-editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) expression and neutrophil-lymphocyte ratio (NLR).
Methods To assess the effectiveness of FTD/TPI in CRC patients, we retrospectively analyzed 72 CRC patients at Okayama University Hospital from 2014 to 2022.
Results Adding bevacizumab to FTD/TPI resulted in a more prolonged progression-free survival (PFS), consistent with the SUNLIGHT study findings (p = 0.0028). Among the participants, those with a high NLR had a shorter PFS (p = 0.0395). Moreover, high ADAR1 expression was associated with longer PFS (p = 0.0151). In multivariate analysis, low ADAR1 (HR = 3.43, p = 0.01) and absence of bevacizumab (HR = 4.25, p = 0.01) were identified as factors shortening PFS. The high ADAR1 group demonstrated fewer cases of progressive disease and a higher proportion of stable disease than the low ADAR1 group (p = 0.0288). Low NLR and high ADAR1 were predictive markers of prolonged PFS in the bevacizumab-treated group (p = 0.0036).
ConclusionLow NLR and high ADAR1 were predictive markers for a positive response to the FTD/TPI plus bevacizumab regimen associated with prolonged PFS. The FTD/TPI plus bevacizumab regimen should be proactively implemented in the low NLR and high ADAR1 subgroups. en-copyright= kn-copyright= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakedaSho en-aut-sei=Takeda en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UmedaHibiki en-aut-sei=Umeda en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriwakeKazuya en-aut-sei=Moriwake en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KayanoMasashi en-aut-sei=Kayano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakuraiYuya en-aut-sei=Sakurai en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraShunsuke en-aut-sei=Nakamura en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakahashiMasafumi en-aut-sei=Takahashi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NittaKaori en-aut-sei=Nitta en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KishimotoHiroyuki en-aut-sei=Kishimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 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=18 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=19 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=20 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=21 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=22 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=23 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=15 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=24 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=ADAR1 kn-keyword=ADAR1 en-keyword=Colorectal cancer kn-keyword=Colorectal cancer en-keyword=Biomarker kn-keyword=Biomarker en-keyword=Trifluridine/tipiracil kn-keyword=Trifluridine/tipiracil END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=1 article-no= start-page=e12512 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250109 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nicotine dependence based on the tobacco dependence screener among heated tobacco products users in Japan, 2022-2023: The JASTIS study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heated tobacco products (HTPs) are nicotine-containing products similar to cigarettes and are widely used in Japan. However, there has been insufficient research on nicotine dependence associated with HTP use. This study investigated the association of the types of individuals who smoked with the prevalence of nicotine dependence. We utilized data from the Japan Survey on Tobacco and Health (JASTIS). A total of 7969 participants who currently smokes was selected from the 2022 and 2023 survey respondents for the analysis. Nicotine dependence was defined as a score of 5 or higher on the Tobacco Dependence Screener (TDS). The prevalence of nicotine dependence was 43.0% (3473/8077) among all participants who smoked, 42.9% (1479/3447) among those who used cigarettes, 44.2% (760/1720) among those who used two products, and 43.0% (1206/2802) among those who used HTPs. The prevalence of nicotine dependence was statistically higher in the participants who used two products than in cigarettes (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.04-1.33). When classified by temperature, participants who used of two products (high-temp and low-temp) and those using participants who used HTPs (high-temp) had higher ORs for prevalent nicotine dependence (OR, 1.31 [95% CI, 1.14-1.51]) and (OR, 1.12 [95% CI, 1.00-1.25], respectively) compared to participants who used cigarettes. Additionally, the ORs for prevalent nicotine dependence increased with the number of tobacco sticks smoked per day. These results suggest that HTP use, particularly high-temperature HTPs use, and a higher number of tobacco sticks smoked is associated with nicotine dependence. en-copyright= kn-copyright= en-aut-name=KitajimaTakuma en-aut-sei=Kitajima en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=TabuchiTakahiro en-aut-sei=Tabuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=Division of Epidemiology, Department of Health Informatics and Public Health, School of Public Health, Tohoku University Graduate School of Medicine kn-affil= en-keyword=cross-sectional survey kn-keyword=cross-sectional survey en-keyword= heated tobacco products kn-keyword= heated tobacco products en-keyword= logistic regression kn-keyword= logistic regression en-keyword= nicotine dependence kn-keyword= nicotine dependence en-keyword= tobacco dependence screener kn-keyword= tobacco dependence screener END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=24 article-no= start-page=4383 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association Between Change in Prognostic Nutritional Index During Neoadjuvant Therapy and Dental Occlusal Support in Patients with Esophageal Cancer Under Neoadjuvant Therapy: A Retrospective Longitudinal Pilot Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: A high prognostic nutritional index (PNI) is associated with good prognosis in patients with esophageal cancer. However, nutritional status often decreases during neoadjuvant therapy. Functional tooth units (FTUs) provide an index for the status of posterior occlusal support. We have previously reported that low PNI is related to low FTUs. Objectives: The purpose of this study was to retrospectively examine whether the status of occlusal support relates to changes in PNI during neoadjuvant therapy in patients with esophageal cancer. Methods: This study included 34 patients who underwent neoadjuvant therapy before esophagectomy (32 men, 2 women; age, 36-82 years) in 2012 at Okayama University Hospital. Patients were divided into the good occlusal support group (FTUs >= 11, n = 18) or poor occlusal support group (FTUs < 11, n = 16), and changes in PNI during neoadjuvant therapy were investigated. Results: PNI decreased significantly after neoadjuvant therapy, particularly in the good occlusal support group, and became more dispersed after neoadjuvant therapy. Decreases in PNI after neoadjuvant therapy showed a significant positive correlation with good occlusal support by multiple regression analysis (p = 0.03). The proportions of patients provided with nutritional intervention (p = 0.02) or early dental intervention (p = 0.04) were lower in the good occlusal support group than in the poor occlusal support group. Conclusions: Even in patients with esophageal cancer with good occlusal support experienced significant declines in PNI during neoadjuvant therapy, potentially due to delayed nutritional and dental interventions. Early multidisciplinary interventions are thus recommended for all patients, regardless of preoperative dental or nutritional status. en-copyright= kn-copyright= en-aut-name=Yamanaka-KohnoReiko en-aut-sei=Yamanaka-Kohno en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=Inoue-MinakuchiMami en-aut-sei=Inoue-Minakuchi en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokoiAya en-aut-sei=Yokoi en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital 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 Oral Rehabilitation and Regenerative Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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 Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=prognostic factors kn-keyword=prognostic factors en-keyword=nutrition kn-keyword=nutrition en-keyword=neoadjuvant therapy kn-keyword=neoadjuvant therapy en-keyword=dental occlusion kn-keyword=dental occlusion END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue= article-no= start-page=1439705 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HOMA-beta independently predicts survival in patients with advanced cancer on treatment with immune checkpoint inhibitors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although immune checkpoint inhibitors (ICIs) are effective cancer drugs, ICI-induced diabetes is a rare but a life-threatening adverse event for patients. The deleterious action of ICI on pancreatic beta-cell function is a concern. However, the influence of ICI on insulin synthesis and secretion in patients with cancer without diabetes remains unknown.
Methods: This study included 87 patients diagnosed with advanced cancer. Glucose metabolism markers (HbA1c, HOMA-IR) and indicators of insulin secretory capacity (HOMA-beta, C-peptide) were prospectively evaluated in patients with ICI-treated cancers to determine their association with cancer prognosis.
Results: Patients with overall survival (OS) >= 7 months had substantially higher HOMA-beta levels at baseline (p=0.008) and 1 month after ICI administration (p=0.006) compared to those with OS <7 months. The median OS was significantly longer in patients with HOMA-beta >= 64.24 (13 months, 95%CI: 5.849-20.151, 37 events) than in those with HOMA-beta < 64.24 (5 months, 95%CI: 3.280-6.720, 50 events) (p=0.013). Further, the median progression-free survival (PFS) was significantly longer in patients with HOMA-beta >= 66.43 (4 months, 95%CI: 3.073-4.927, 33 events) than in those with HOMA-beta < 66.43 (2 months, 95%CI: 1.410-2.590, 54 events) (p=0.025). Additionally, multivariable logistic regression analysis revealed that a HOMA-beta value >= 64.24 independently predicted longer OS in ICI-treated patients.
Conclusions: Pre-ICI HOMA-beta level is linked to longer OS in ICI-treated patients. This connection is significant and shows that insulin secretory capacity may predict ICI efficacy. 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=TakamotoAtsushi en-aut-sei=Takamoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanzakiHiromitsu en-aut-sei=Kanzaki en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NodaYohei en-aut-sei=Noda en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KagawaSyunsuke en-aut-sei=Kagawa en-aut-mei=Syunsuke 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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Fukuyama City Hospital kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=5 en-affil=Department of Urology, Fukuyama City Hospital 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 Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anti-PD1 immune checkpoint inhibitors kn-keyword=anti-PD1 immune checkpoint inhibitors en-keyword= insulin secretory capacity kn-keyword= insulin secretory capacity en-keyword= cancer prognosis kn-keyword= cancer prognosis en-keyword= insulin secretion kn-keyword= insulin secretion en-keyword= glucose metabolism markers kn-keyword= glucose metabolism markers END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=23 article-no= start-page=7078 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Characteristics of Persistent Hypophosphatasemia Uncovered in Adult Patients: A Retrospective Study at a Japanese Tertiary Hospital en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Hypophosphatasemia is often overlooked despite its potential to indicate underlying pathologies. The aim of this study was to determine the prevalence of persistent hypophosphatasemia in a large, urban, multi-specialty hospital population and characterize the clinical and laboratory findings in adult patients with this condition. Methods: In this retrospective observational study, the results of 424,434 alkaline phosphatase (ALP) tests in 50,136 patients aged >= 18 years that were performed at Okayama University Hospital between July 2020 and October 2023 were analyzed. Persistent hypophosphatasemia was defined as consistently low ALP levels (<= 40 IU/L) for 28 days with a minimum recorded level of <= 35 IU/L. Results: Persistent hypophosphatasemia was detected in 273 patients (0.54% of the tested patients), and the patients with persistent hypophosphatasemia included a higher proportion of females (72.5% vs. 52.9% in the people without persistent hypophosphatasemia; chi-squared test, p < 0.01) and had a younger median age (51 years vs. 63 years; Mann-Whitney U test, p < 0.01) than those in the overall tested population. The common causes of persistent hypophosphatasemia were cancer (30%), glucocorticoid use (21%), and immunosuppressants (16%). Notably, 38 patients (14%) had no apparent cause for low ALP values. These patients were categorized on the basis of their clinical characteristics, with some patients presenting symptoms potentially related to adult hypophosphatasia. Conclusions: This study provides prevalence and insights into the causes and characteristics of persistent hypophosphatasemia in a Japanese tertiary care setting. While most cases were associated with known causes, patients with unexplained hypophosphatasemia and symptoms such as chronic pain, muscle weakness, and general fatigue could have adult hypophosphatasia. In such cases, comprehensive evaluation and further investigation for hypophosphatasia should be considered. Persistent hypophosphatasemia of undetermined etiology could be a crucial initial step in diagnostic algorithms for this condition. en-copyright= kn-copyright= en-aut-name=FujiwaraShintaro en-aut-sei=Fujiwara en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FurukawaMasanori en-aut-sei=Furukawa en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HigashikageAkihito en-aut-sei=Higashikage en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=chronic fatigue syndrome kn-keyword=chronic fatigue syndrome en-keyword=chronic pain kn-keyword=chronic pain en-keyword=hypophosphatasemia kn-keyword=hypophosphatasemia en-keyword=alkaline phosphatase kn-keyword=alkaline phosphatase en-keyword=hypophosphatasia kn-keyword=hypophosphatasia END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=24 article-no= start-page=2045 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=iPSC-Derived Biological Pacemaker-From Bench to Bedside en-subtitle= kn-subtitle= en-abstract= kn-abstract=Induced pluripotent stem cell (iPSC)-derived biological pacemakers have emerged as an alternative to traditional electronic pacemakers for managing cardiac arrhythmias. While effective, electronic pacemakers face challenges such as device failure, lead complications, and surgical risks, particularly in children. iPSC-derived pacemakers offer a promising solution by mimicking the sinoatrial node's natural pacemaking function, providing a more physiological approach to rhythm control. These cells can differentiate into cardiomyocytes capable of autonomous electrical activity, integrating into heart tissue. However, challenges such as achieving cellular maturity, long-term functionality, and immune response remain significant barriers to clinical translation. Future research should focus on refining gene-editing techniques, optimizing differentiation, and developing scalable production processes to enhance the safety and effectiveness of these biological pacemakers. With further advancements, iPSC-derived pacemakers could offer a patient-specific, durable alternative for cardiac rhythm management. This review discusses key advancements in differentiation protocols and preclinical studies, demonstrating their potential in treating dysrhythmias. en-copyright= kn-copyright= en-aut-name=VoQuan Duy en-aut-sei=Vo en-aut-mei=Quan Duy 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=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro 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=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AmiokaNaofumi en-aut-sei=Amioka en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=sinoatrial node kn-keyword=sinoatrial node en-keyword=HCN channels kn-keyword=HCN channels en-keyword=induced pluripotent stem cell kn-keyword=induced pluripotent stem cell END start-ver=1.4 cd-journal=joma no-vol=103 cd-vols= no-issue=50 article-no= start-page=e40849 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relevance of oxidative stress for small intestinal injuries induced by nonsteroidal anti-inflammatory drugs: A multicenter prospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Several reports revealed that oxidative stress was involved in the mouse model of nonsteroidal anti-inflammatory drug (NSAIDs)-induced small intestinal mucosal injuries. Thus, we aimed to investigate in the prospective clinical study, that the relevance of oxidative stress balance in small intestinal mucosal injury in NSAIDs users. We prospectively included 60 patients who had been taking NSAIDs continuously for more than 3 months and exhibited obscure gastrointestinal bleeding (number UMIN 000011775). Small intestinal mucosal injuries were assessed by capsule endoscopy (CE), and reactive oxygen metabolites (d-ROMs) levels and oxidant capacity (OXY) adsorbent test were performed to investigate the relevance of oxidative stress balance. More than half of the patients (N = 32, 53%) had small intestinal mucosal injuries by CE, and 14 patients (24%) had ulcers. The incidence of ulcers was relatively higher in nonaspirin users. Serum OXY levels were significantly lower in the mucosal injury group (P = .02), and d-ROM levels were significantly higher in the ulcer group (P < .01). In aspirin users, d-ROM and OXY levels did not differ significantly with respect to mucosal injuries or ulcers. However, in nonaspirin users, OXY level was significantly lower in the mucosal injury group (P = .04), and d-ROM levels were significantly higher in the ulcer group (P = .02). Nonaspirin NSAIDs-induced intestinal mucosal injury is associated with antioxidant systems, resulting in increased oxidative stress. en-copyright= kn-copyright= en-aut-name=BabaYuki en-aut-sei=Baba en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=HoriiJoichiro en-aut-sei=Horii en-aut-mei=Joichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiSakuma en-aut-sei=Takahashi en-aut-mei=Sakuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaiDaisuke en-aut-sei=Kawai en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KobayashiSayo en-aut-sei=Kobayashi en-aut-mei=Sayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Japanese Red Cross Himeji Hospital 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 Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=8 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=capsule endoscopy kn-keyword=capsule endoscopy en-keyword=NSAIDs kn-keyword=NSAIDs en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=small intestinal mucosal injury kn-keyword=small intestinal mucosal injury END start-ver=1.4 cd-journal=joma no-vol=169 cd-vols= no-issue=1 article-no= start-page=e16291 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241222 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploring the Role of Ccn3 in Type III Cell of Mice Taste Buds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Different taste cells express unique cell-type markers, enabling researchers to distinguish them and study their functional differentiation. Using single-cell RNA-Seq of taste cells in mouse fungiform papillae, we found that Cellular Communication Network Factor 3 (Ccn3) was highly expressed in Type III taste cells but not in Type II taste cells. Ccn3 is a protein-coding gene involved in various biological processes, such as cell proliferation, angiogenesis, tumorigenesis, and wound healing. Therefore, in this study, we aimed to explore the expression and function of Ccn3 in mouse taste bud cells. Using reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry (IHC), we confirmed that Ccn3 was predominantly expressed in Type III taste cells. Through IHC, quantitative real-time RT-PCR, gustatory nerve recordings, and short-term lick tests, we observed that Ccn3 knockout (Ccn3-KO) mice did not exhibit any significant differences in the expression of taste cell markers and taste responses compared to wild-type controls. To explore the function of Ccn3 in taste cells, bioinformatics analyses were conducted and predicted possible roles of Ccn3 in tissue regeneration, perception of pain, protein secretion, and immune response. Among them, an immune function is the most plausible based on our experimental results. In summary, our study indicates that although Ccn3 is strongly expressed in Type III taste cells, its knockout did not influence the basic taste response, but bioinformatics provided valuable insights into the possible role of Ccn3 in taste buds and shed light on future research directions. en-copyright= kn-copyright= en-aut-name=WangKuanyu en-aut-sei=Wang en-aut-mei=Kuanyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HorieKengo en-aut-sei=Horie en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=bioinformatics kn-keyword=bioinformatics en-keyword=Ccn3 kn-keyword=Ccn3 en-keyword=Type III taste cell kn-keyword=Type III taste cell END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=3 article-no= start-page=620 end-page=626 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=2023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=All-in-one terahertz taste sensor: integrated electronic and bioelectronic tongues en-subtitle= kn-subtitle= en-abstract= kn-abstract=Taste sensors, also known as electronic tongues or bioelectronic tongues, are designed to evaluate food and beverages, as well as for medical diagnostics. These devices mimic the ability of the human tongue to detect and identify different tastes in liquid samples, such as sweet, sour, salty, bitter, and umami. In this study, a novel all-in-one terahertz taste sensor was proposed, which differs from traditional electrochemical approaches. This sensor utilizes terahertz technology for imaging and sensing chemical reactions on the terahertz semiconductor emitter surface. The surface can be functionalized with ion-sensitive membranes, proteins, DNA aptamers, and organic receptors, enabling the detection of various substances, such as solution pH, physiological ions, sugars, toxic chemicals, drugs, and explosives. Terahertz taste sensors offer several advantages, including being label-free, high sensitivity and selectivity, rapid response, minimal sample consumption, and the ability to detect non-charged chemical substances. By integrating multiple receptors or sensing materials on a single chip, the all-in-one terahertz taste sensor has significant potential for future taste substance detection, nutrition evaluation, metabolite and drug monitoring, and biomarker sensing. en-copyright= kn-copyright= en-aut-name=WangJin en-aut-sei=Wang en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakaiKenji en-aut-sei=Sakai en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KiwaToshihiko en-aut-sei=Kiwa en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=1 article-no= start-page=65 end-page=73 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of Automatic Inspection Systems for WRS2020 Plant Disaster Prevention Challenge Using Image Processing en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this article, an approach used for the inspection tasks in the WRS2020 Plant Disaster Prevention Challenge is explained. The tasks were categorized into three categories: reading pressure gauges, inspecting rust on a tank, and inspecting cracks in a tank. For reading pressure gauges, the “you only look once” algorithm was used to focus on a specific pressure gauge and check the pressure gauge range strings on the gauge using optical character recognition algorithm. Finally, a previously learned classifier was used to read the values shown in the gauge. For rust inspection, image processes were used to focus on a target plate that may be rusted for rust detection. In particular, it was necessary to report the rust area and distribution type. Thus, the pixel ratio and grouping of rust were used to count the rust. The approach for crack inspection was similar to that for rust. The target plate was focused on first, and then the length of the crack was measured using image processing. Its width was not measured but was calculated using the crack area and length. For each system developed to approach each task, the results of the preliminary experiment and those of WRS2020 are shown. Finally, the approaches are summarized, and planned future work is discussed. en-copyright= kn-copyright= en-aut-name=ShimizuYuya en-aut-sei=Shimizu en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KamegawaTetsushi en-aut-sei=Kamegawa en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangYongdong en-aut-sei=Wang en-aut-mei=Yongdong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TamuraHajime en-aut-sei=Tamura en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TeshimaTaiga en-aut-sei=Teshima en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoSota en-aut-sei=Nakano en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TadaYuki en-aut-sei=Tada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoDaiki en-aut-sei=Nakano en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SasakiYuichi en-aut-sei=Sasaki en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SekitoTaiga en-aut-sei=Sekito en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UtsumiKeisuke en-aut-sei=Utsumi en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagaoRai en-aut-sei=Nagao en-aut-mei=Rai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SembaMizuki en-aut-sei=Semba en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Okayama University kn-affil= affil-num=4 en-affil=Okayama University kn-affil= affil-num=5 en-affil=Okayama University kn-affil= affil-num=6 en-affil=Okayama University kn-affil= affil-num=7 en-affil=Okayama University kn-affil= affil-num=8 en-affil=Okayama University kn-affil= affil-num=9 en-affil=Okayama University kn-affil= affil-num=10 en-affil=Okayama University kn-affil= affil-num=11 en-affil=Okayama University kn-affil= affil-num=12 en-affil=Okayama University kn-affil= affil-num=13 en-affil=Okayama University kn-affil= en-keyword=WRS2020 kn-keyword=WRS2020 en-keyword=image processing kn-keyword=image processing en-keyword=auto inspection kn-keyword=auto inspection en-keyword=YOLO kn-keyword=YOLO en-keyword=OCR kn-keyword=OCR END start-ver=1.4 cd-journal=joma no-vol=222 cd-vols= no-issue= article-no= start-page=115374 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Environmental water in Kolkata is suitable for the survival of Vibrio cholerae O1 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Many patients with cholera emerge in Kolkata, India throughout the year. Such emergency indicates that cholera toxin-producing Vibrio cholerae O1 (toxigenic V. cholerae O1) are widespread in Kolkata. This suggests that the suitable conditions for replication of toxigenic V. cholerae O1 is provided in Kolkata. In previous studies, we found that the replication rate of toxigenic V. cholerae O1 is low in the low ionic aqueous solution. Then we measured the ion concentration in the environmental water of Kolkata. As a control, we measured them in Japanese environmental water. The ion concentration in the environmental water of Kolkata was significantly high. Then, we examined the survival of toxigenic V. cholerae O1 in groundwater from Kolkata and found that V. cholerae O1 survive for long time in the solution but not in the solution diluted with Milli Q water. In addition, we found that V. cholerae O1 proliferated in environmental water of Kolkata to which a small amount of nutrient was added, but did not grow in the environmental water diluted with water to which the same amount of nutrient was added. These results indicate that the environmental water from Kolkata is suitable for survival of V. cholerae O1. en-copyright= kn-copyright= en-aut-name=TakahashiEizo en-aut-sei=Takahashi en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitaharaKei en-aut-sei=Kitahara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChowdhuryGoutam en-aut-sei=Chowdhury en-aut-mei=Goutam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MukhopadhyayAsish K. en-aut-sei=Mukhopadhyay en-aut-mei=Asish K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DuttaShanta en-aut-sei=Dutta en-aut-mei=Shanta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OchiSadayuki en-aut-sei=Ochi en-aut-mei=Sadayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKeinosuke en-aut-sei=Okamoto en-aut-mei=Keinosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India kn-affil= affil-num=2 en-affil=Collaborative Research Center of Okayama University for Infectious Diseases in India kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences of Okayama University kn-affil= affil-num=4 en-affil=National Institute of Cholera and Enteric Diseases kn-affil= affil-num=5 en-affil=National Institute of Cholera and Enteric Diseases kn-affil= affil-num=6 en-affil=National Institute of Cholera and Enteric Diseases kn-affil= affil-num=7 en-affil=Department of Health Pharmacy, Yokohama University of Pharmacy kn-affil= affil-num=8 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences of Okayama University kn-affil= en-keyword=Environmental water kn-keyword=Environmental water en-keyword=Ion kn-keyword=Ion en-keyword=Prevalence kn-keyword=Prevalence en-keyword=Survival kn-keyword=Survival en-keyword=Vibrio cholerae kn-keyword=Vibrio cholerae END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=21 article-no= start-page=2875 end-page=2884 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endoscopic and Histological Gastritis in University Students with Helicobacter pylori Infection en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Although the characteristics of Helicobacter pylori infection have been extensively reported, there is a lack of consensus regarding its characteristics in young adults. The present study examined the endoscopic and histological characteristics of young adults who underwent eradication therapy for H. pylori infection.
Methods We examined the H. pylori infection status of first-year students at Okayama University School of Medicine and Dentistry between 2014 and 2020. A total of 152 (6.8%) students who were positive for H. pylori antibody or pepsinogen tests were enrolled in the study. Among them, 107 students underwent endoscopy, and their biopsy samples were investigated. Seventy-five students were diagnosed with H. pylori infections.
Results Of 75 H. pylori-positive patients, 57 (76.0%) had endoscopic atrophic gastritis, and 42 (56.0%) had histological atrophy. A few patients had severe atrophic gastritis. All 65 patients who underwent an eradication assessment were successfully treated. After successful eradication, 26 patients underwent endoscopic follow-up. The mean follow-up period was 32.9 months. A histological evaluation revealed that gastric antrum atrophy had subsided in 11 of 14 patients, and atrophy in the lesser curvature of the gastric body had subsided in 7 of 8 patients.
Conclusion More than half of young adults with H. pylori infection had atrophic gastritis. We found mild atrophy in young adults, which subsided shortly after eradication treatment. This study provides a foundation for future studies to evaluate the validity of eradication therapy in preventing gastric cancer in patients. en-copyright= kn-copyright= en-aut-name=OkanoueShotaro en-aut-sei=Okanoue en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= en-aut-name=ObayashiYuka en-aut-sei=Obayashi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AbeMakoto en-aut-sei=Abe en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KanzakiHiromitsu en-aut-sei=Kanzaki en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 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=12 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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 Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, 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 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 Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=atrophic gastritis kn-keyword=atrophic gastritis en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=Helicobacter pylori kn-keyword=Helicobacter pylori en-keyword=young adults kn-keyword=young adults en-keyword=eradication kn-keyword=eradication END start-ver=1.4 cd-journal=joma no-vol=145 cd-vols= no-issue=8 article-no= start-page=881 end-page=896 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=Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD. en-copyright= kn-copyright= en-aut-name=KambaraYui en-aut-sei=Kambara en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunihiroMari en-aut-sei=Kunihiro en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OyamaTadashi en-aut-sei=Oyama en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=SatoAyame en-aut-sei=Sato en-aut-mei=Ayame 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=PeltierDaniel en-aut-sei=Peltier en-aut-mei=Daniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 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=16 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=17 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ReddyPavan en-aut-sei=Reddy en-aut-mei=Pavan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshinobuMaeda en-aut-sei=Yoshinobu en-aut-mei=Maeda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Medical School 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 Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Microbiology and Genetics, Okayama University Graduate School of Health Sciences 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, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Simon Cancer Center, Indiana University School of Medicine 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=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=17 en-affil=Division of Blood Transfusion, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=20 en-affil=Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine kn-affil= affil-num=21 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=2 article-no= start-page=249 end-page=260 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Ischemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD.
Methods: Previously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1?/?) mice.
Results: NR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LTｘ from Nr4a1?/? donors significantly improved pulmonary graft function compared to wild-type donors. Histological analysis showed decreased microvascular endothelial cell death, neutrophil infiltration, and albumin leakage. Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1?/? donors, correlating with diminished pulmonary edema. However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1?/? recipient.
Conclusions: Donor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD. en-copyright= kn-copyright= en-aut-name=KawanaShinichi en-aut-sei=Kawana en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaueTomohisa en-aut-sei=Sakaue en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoKohei en-aut-sei=Hashimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChoshiHaruki en-aut-sei=Choshi en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=OhtaniShinji en-aut-sei=Ohtani 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=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=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= affil-num=1 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=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 Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine kn-affil= affil-num=4 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=5 en-affil=Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University School of Medicine kn-affil= affil-num=6 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=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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University kn-affil= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 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=12 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 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=ischemia-reperfusion injury kn-keyword=ischemia-reperfusion injury en-keyword=donation after circulatory death kn-keyword=donation after circulatory death en-keyword=nuclear receptor subfamily 4 group A member 1 kn-keyword=nuclear receptor subfamily 4 group A member 1 en-keyword=endothelial cell kn-keyword=endothelial cell END start-ver=1.4 cd-journal=joma no-vol=226 cd-vols= no-issue= article-no= start-page=158 end-page=166 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240915 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The impact of cumulus cell viability and pre-culture with the healthy cell mass on brilliant cresyl blue (BCB) staining assessment and meiotic competence of suboptimal porcine oocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives of the present study were to investigate the characteristics including glucose-6-phosphate dehydrogenase activity, as determined by Brilliant Cresyl Blue (BCB) staining, of suboptimal porcine oocytes and to enhance the meiotic competence of those through pre-culture with cumulus cell masses (CCMs). Percentage of oocyte-cumulus complexes (OCCs) derived from small follicles (SF; <3 mm in diameter) containing the oocytes that were assessed as BCB-negative (BCB-) was significantly higher than those derived from medium follicles (MF; 3?6 mm in diameter). Degrees of dead cumulus cells were significantly higher in OCCs containing BCB- oocytes, regardless of the origin of OCCs (MF vs. SF), than those containing BCB-positive (BCB+) ones. Exposing OCCs containing BCB+ oocytes to the apoptosis inducer, carbonyl cyanide m-chlorophenylhydrazone, for 20 h significantly induced the transition to BCB- and meiotic progression of exposed OCCs were significantly reduced in both SF and MF derived ones. Transit of BCB- oocytes to BCB+ was induced when OCCs were pre-cultured with CCMs of MF derived OCCs containing BCB+ oocytes for 20 h before IVM. This pre-culture also significantly increased the meiotic competence of BCB- oocytes, particularly in SF derived ones. However, reactive oxygen species levels were significantly higher in BCB+ oocytes as compared with BCB- ones, regardless of pre-culture with CCMs, whereas no significant differences were found in the ATP contents among the treatment groups. In conclusion, the BCB result of oocytes could be regulated by the healthy status and content of surrounding cumulus cells and the meiotic competence of suboptimal BCB- porcine oocytes is improved by pre-culture with healthy CCMs. en-copyright= kn-copyright= en-aut-name=FonsekaWanniarachchige Tharindu Lakshitha en-aut-sei=Fonseka en-aut-mei=Wanniarachchige Tharindu Lakshitha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DoSon Quang en-aut-sei=Do en-aut-mei=Son Quang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=VanPhong Ngoc en-aut-sei=Van en-aut-mei=Phong Ngoc kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NguyenHai Thanh en-aut-sei=Nguyen en-aut-mei=Hai Thanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FunahashiHiroaki en-aut-sei=Funahashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Oocytes kn-keyword=Oocytes en-keyword=Meiotic competence kn-keyword=Meiotic competence en-keyword=Brilliant cresyl blue kn-keyword=Brilliant cresyl blue en-keyword=Cumulus cells kn-keyword=Cumulus cells END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=1 article-no= start-page=102494 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=Cryptococcal prostatitis in an immunocompromised patient with tocilizumab and glucocorticoid therapy: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cryptococcus prostatitis is an uncommon manifestation of cryptococcal infection that occurs mostly in immunocompromised patients. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, has been associated with an increased risk of cryptococcal infections. However, there have been no documented cases of cryptococcal prostatitis in patients receiving tocilizumab therapy. We report a case of cryptococcal prostatitis in a 72-year-old man treated with glucocorticoids and tocilizumab for giant cell arteritis and granulomatosis with polyangiitis. The patient presented dysuria and his serum level of prostate-specific antigen was elevated. Magnetic resonance imaging revealed a prostate mass, and a prostate biopsy was performed, leading to a pathologic diagnosis of cryptococcal prostatitis. Fungal cultures for blood and urine were negative, while the cryptococcal antigen for both serum and urine showed positive results. There were no particular findings in the pulmonary and central nervous systems. The patient was successfully treated with oral fluconazole (400 mg/day) and was discharged. Although cryptococcal prostatitis is a rare entity, clinicians should note that an immunosuppressed patient may develop such a difficult-to-diagnose disease. en-copyright= kn-copyright= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke 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=KatoAtsushi en-aut-sei=Kato en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuyamaAtsuhito en-aut-sei=Suyama en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OnoSawako en-aut-sei=Ono en-aut-mei=Sawako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical 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 Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, 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 Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cryptococcosis kn-keyword=Cryptococcosis en-keyword=Fluconazole kn-keyword=Fluconazole en-keyword=Glucocorticoids kn-keyword=Glucocorticoids en-keyword=Prostatitis kn-keyword=Prostatitis en-keyword=Tocilizumab kn-keyword=Tocilizumab END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=e70097 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Eyelid Spindle Cell Lipoma: Case Report and Review of Three Patients in Literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 39-year-old woman presented a saucer-shaped mass in the left upper eyelid and underwent the extirpation at local anesthesia. Pathologically, collagen fibers, capillaries, small vessels, and CD34-positive spindle cells were dispersed among mature adipose tissues, indicative of spindle cell lipoma. Long-lasting cyst-like eyelid masses would be usually dermoid cysts, and spindle cell lipoma would be listed as a rare pathological diagnosis in differential diagnoses of cyst-like lesions in the upper and lower eyelid. 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=YamadaKiyoshi en-aut-sei=Yamada en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MonobeYasumasa en-aut-sei=Monobe en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Plastic and Reconstructive Surgery, Kousei Hospital kn-affil= affil-num=3 en-affil=Department of Pathology, General Medical Center, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=CD34 kn-keyword=CD34 en-keyword=eyelid kn-keyword=eyelid en-keyword=orbital bony edge kn-keyword=orbital bony edge en-keyword=pathology kn-keyword=pathology en-keyword=spindle cell lipoma kn-keyword=spindle cell lipoma END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=1 article-no= start-page=11 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230323 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mutation and apoptosis are well-coordinated for protecting against DNA damage-inducing toxicity in Drosophila en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Apoptotic cell death is an important survival system for multicellular organisms because it removes damaged cells. Mutation is also a survival method for dealing with damaged cells in multicellular and also unicellular organisms, when DNA lesions are not removed. However, to the best of our knowledge, no reports have comprehensively explored the direct relationship between apoptosis and somatic cell mutations induced by various mutagenic factors.
Results Mutation was examined by the wing-spot test, which is used to detect somatic cell mutations, including chromosomal recombination. Apoptosis was observed in the wing discs by acridine orange staining in situ. After treatment with chemical mutagens, ultraviolet light (UV), and X-ray, both the apoptotic frequency and mutagenic activity increased in a dose-dependent manner at non-toxic doses. When we used DNA repair-deficient Drosophila strains, the correlation coefficient of the relationship between apoptosis and mutagenicity, differed from that of the wild-type. To explore how apoptosis affects the behavior of mutated cells, we determined the spot size, i.e., the number of mutated cells in a spot. In parallel with an increase in apoptosis, the spot size increased with MNU or X-ray treatment dose-dependently; however, this increase was not seen with UV irradiation. In addition, BrdU incorporation, an indicator of cell proliferation, in the wing discs was suppressed at 6 h, with peak at 12 h post-treatment with X-ray, and that it started to increase again at 24 h; however, this was not seen with UV irradiation.
Conclusion Damage-induced apoptosis and mutation might be coordinated with each other, and the frequency of apoptosis and mutagenicity are balanced depending on the type of DNA damage. From the data of the spot size and BrdU incorporation, it is possible that mutated cells replace apoptotic cells due to their high frequency of cell division, resulting in enlargement of the spot size after MNU or X-ray treatment. We consider that the induction of mutation, apoptosis, and/or cell growth varies in multi-cellular organisms depending on the type of the mutagens, and that their balance and coordination have an important function to counter DNA damage for the survival of the organism. en-copyright= kn-copyright= en-aut-name=Toyoshima-SasataniMegumi en-aut-sei=Toyoshima-Sasatani en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ImuraFumika en-aut-sei=Imura en-aut-mei=Fumika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamatakeYuko en-aut-sei=Hamatake en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukunagaAkihiro en-aut-sei=Fukunaga en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NegishiTomoe en-aut-sei=Negishi en-aut-mei=Tomoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=School of Nursing, Osaka City University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Drosophila kn-keyword=Drosophila en-keyword=Apoptosis kn-keyword=Apoptosis en-keyword=Mutation kn-keyword=Mutation en-keyword=Larval wing disc kn-keyword=Larval wing disc en-keyword=X-ray kn-keyword=X-ray en-keyword=Ultraviolet kn-keyword=Ultraviolet en-keyword=Alkylating agents kn-keyword=Alkylating agents en-keyword=Tobacco smoke kn-keyword=Tobacco smoke en-keyword=Acridine orange kn-keyword=Acridine orange en-keyword=BrdU kn-keyword=BrdU END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=3 article-no= start-page=769 end-page=774 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Review: Nicotinic acetylcholine receptors to regulate important brain activity?what occurs at the molecular level? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Herein, we briefly review the role of nicotinic acetylcholine receptors in regulating important brain activity by controlled release of acetylcholine from subcortical neuron groups, focusing on a microscopic viewpoint and considering the nonlinear dynamics of biological macromolecules associated with neuron activity and how they give rise to advanced brain functions of brain. en-copyright= kn-copyright= en-aut-name=NaraShigetoshi en-aut-sei=Nara en-aut-mei=Shigetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamagutiYutaka en-aut-sei=Yamaguti en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsudaIchiro en-aut-sei=Tsuda en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Information Engineering, Fukuoka Institute of Technology kn-affil= affil-num=3 en-affil=Chubu University Academy of Emerging Sciences/Center for Mathematical Science and Artificial Intelligence, Chubu University kn-affil= en-keyword=Neuromodulator kn-keyword=Neuromodulator en-keyword=Nichotinic kn-keyword=Nichotinic en-keyword=Acetylcholine kn-keyword=Acetylcholine en-keyword=Receptors kn-keyword=Receptors en-keyword=Brain activity kn-keyword=Brain activity END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=01 article-no= start-page=E90 end-page=E96 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differences in color between early gastric cancer and cancer-suspected non-cancerous mucosa on linked color imaging en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and study aims?Linked color imaging (LCI) can enhance the original color of each area and may useful to detect tumorous lesions during esophagogastroduodenoscopy. However, LCI may also enhance cancer-suspected non-cancerous regional color change. We conducted a retrospective image analysis to investigate the color characteristics of early gastric cancer (EGC) and cancer-suspected non-cancerous mucosa (CSM) in LCI.
Methods?LCI images of both EGC and CSM were retrospectively collected from the database of the institution. Fifteen endoscopists individually judged each image as EGC or CSM. The color difference between the inside and outside of the lesions was measured by CIE-Lab analysis in both groups and compared.
Results?A total of 245 LCI images of EGC (169) and CSM (76) were extracted and randomly lined for image collection. The test by the endoscopists showed accuracy, sensitivity, and specificity of 64.0?%, 63.7?%, and 64.0?%, respectively. Although the color difference between EGC and CSM was almost the same (12.5 vs. 12.9, not significant), each parameter of ΔL (bright: ?0.3 vs. ?2.7, P ? Conclusions?The total color difference was almost the same between EGC and CSM; however, their color tones were different on linked color imaging. Although the color characteristics of EGC had high specificity, they also had low sensitivity. en-copyright= kn-copyright= en-aut-name=KanzakiHiromitsu en-aut-sei=Kanzaki en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=OkanoueShotaro en-aut-sei=Okanoue en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=8 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Practical Gastrointestinal Endoscopy, 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 Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=04 article-no= start-page=E351 end-page=E357 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Degree of pharyngeal deformation caused by pharyngeal endoscopic submucosal dissection is associated with the incidence of aspiration pneumonia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and study aims?Endoscopic submucosal dissection (ESD) is one of the most minimally invasive treatments for superficial squamous cell cancer of the pharynx. However, aspiration pneumonia (AsP) associated with postoperative deformity of the pharynx may occur. The purpose of this study was to investigate the frequency of AsP and the degree of pharyngeal deformity after pharyngeal ESD.
Patients and methods?This was a retrospective observational study of patients who underwent pharyngeal ESD at Okayama University Hospital between 2006 and 2017.?The degree of pharyngeal deformation was assessed using the pharyngeal deformation grade (PDG). The primary endpoint was the frequency of AsP as a long-term adverse event.
Results?Among the 52 patients enrolled, nine developed aspiration pneumonia, with a 3-year cumulative incidence of 9.0?% (95?% confidence interval [CI], 3.3?%?22.0?%). There were 16, 18, 16, and two patients that had PDG 0, 1, 2, and 3, respectively. Patients with a history of radiotherapy, as a treatment of head and neck cancer (44.4?% vs. 11.6?%; P?=?0.02) and the high PDG group (PDG 2 and 3) (77.8?% vs. 25.6?%; P?=?0.005) had a significantly higher incidence of AsP. The 3-year cumulative incidence rate of AsP after ESD in the high PDG group was significantly higher than that in the low PDG group (PDG 0 and 1) (23.9?% [95?%CI, 9.2.?49.5%] vs. 0?%; P?=?0.03).
Conclusions?The incidence of aspiration pneumonia in the long-term course after pharyngeal ESD was revealed. The incidence of aspiration pneumonia may be associated with pharyngeal deformity, but further studies are needed. en-copyright= kn-copyright= en-aut-name=AbeMakoto en-aut-sei=Abe en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=ObayashiYuka en-aut-sei=Obayashi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BabaYuki en-aut-sei=Baba en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 ORCID= en-aut-name=KanzakiHiromitu en-aut-sei=Kanzaki en-aut-mei=Hiromitu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NodaYohei en-aut-sei=Noda en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MarunakaHidenori en-aut-sei=Marunaka en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=213 end-page=218 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=β-catenin Binds to Gsk-3β in Liquid-Liquid Phase Separation Compartment in HEK293 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Liquid-liquid phase separation (LLPS) has emerged as a significant mechanism for cellular organization, impacting various biological processes, including Wnt/β-catenin signaling. This study investigates the role of LLPS in the regulation of β-catenin in HEK293 cells, particularly in response to Wnt3a signaling. Our findings demonstrate that β-catenin is regulated by LLPS, forming spherical droplets indicative of this phenomenon. Fluorescence recovery after photobleaching (FRAP) assays revealed that these droplets exhibit reversible dynamics, further confirming their phase-separated nature. Importantly, treatment with Wnt3a led to an increase in β-catenin levels, while simultaneously reducing the recovery of fluorescence intensity in FRAP experiments, suggesting that enhanced Wnt signaling may stimulate the release of β-catenin from LLPS. Immunoprecipitation studies indicated that β-catenin binds to glycogen synthase kinase 3β (Gsk-3β) within the LLPS state, highlighting a potential regulatory mechanism whereby LLPS facilitates the phosphorylation and subsequent degradation of β-catenin. The addition of 1,6-hexanediol disrupted the β-catenin/Gsk-3β interaction, reinforcing the idea that LLPS plays a critical role in modulating these biochemical interactions. The findings presented in this study suggest that LLPS is not only crucial for the spatial organization of β-catenin but also serves as a regulatory mechanism for its signaling functions in the Wnt pathway. Given the association of aberrant Wnt signaling with various diseases, including cancer and neurodegenerative disorders, understanding the role of LLPS in this context may provide new insights into therapeutic strategies targeting these pathological conditions. en-copyright= kn-copyright= en-aut-name=KatoMari en-aut-sei=Kato en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanaiAiri en-aut-sei=Tanai en-aut-mei=Airi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuharaYoko en-aut-sei=Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhengXinyu en-aut-sei=Zheng en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SitosariHeriati en-aut-sei=Sitosari en-aut-mei=Heriati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=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 Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital 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=β-catenin kn-keyword=β-catenin en-keyword=Gsk-3β kn-keyword=Gsk-3β en-keyword=LLPS kn-keyword=LLPS en-keyword=Wnt kn-keyword=Wnt END start-ver=1.4 cd-journal=joma no-vol=136 cd-vols= no-issue=3 article-no= start-page=97 end-page=99 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2023 Incentive Award of the Okayama Medical Association in Cardiovascular and Pulmonary Research (2023 Sunada Prize) kn-title=令和５年度岡山医学会賞　胸部・循環研究奨励賞（砂田賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name=谷口暁彦 kn-aut-sei=谷口 kn-aut-mei=暁彦 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科　血液・腫瘍・呼吸器内科学 END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue= article-no= start-page=110572 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=Laparoscopic resection for oesophageal duplication cyst: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Oesophageal duplication cyst is a congenital malformation and rare tumour, clinically manifesting as dysphagia, epigastric pain, or respiratory distress. Duplicate cysts associated with abscess formation or mediastinal penetration and malignancies have been reported, necessitating surgical resection.
Presentation of case: A 55-year-old woman had chest discomfort for 1 year. Preoperative imaging, including computed tomography (CT), upper gastrointestinal endoscopy, and endoscopic ultrasound, revealed a tumour extending from the anterior wall to the lesser curvature of the near the oesophagogastric junction (OGJ) and a suspected mural nodule within the tumour. Contrast-enhanced CT revealed a cystic nodule on the wall of the lesser curvature of the OGJ, with an unclear boundary between the cystic nodule and the oesophageal wall. Magnetic resonance imaging showed an isointense signal on T1-weighted imaging and hyperintensity on T2weighted imaging. Laparoscopic lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed to the confirm mucinous cyst. Pathological findings revealed a cystic lesion in the muscularis propria of the OGJ filled with mucinous components and lined with multilayered columnar epithelial cells. The cyst was diagnosed as a duplicate without malignancy.
Discussion: Since the border between the cyst and the oesophageal walls was unclear, and the cyst potentially contained a malignant component, instead of cystectomy, lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed with oesophagogastric anastomosis using the double-flap technique, tailored specifically for OGJ cancer.
Conclusions: Oesophageal duplication cysts are rare. Lower oesophagectomy and proximal gastrectomy are selective surgical approaches for cyst duplication at the OGJ. en-copyright= kn-copyright= en-aut-name=HamazakiTomohiro en-aut-sei=Hamazaki en-aut-mei=Tomohiro 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=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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= en-keyword=Oesophageal duplication cyst kn-keyword=Oesophageal duplication cyst en-keyword=Laparoscopic surgery kn-keyword=Laparoscopic surgery en-keyword=Lower oesophagectomy kn-keyword=Lower oesophagectomy END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=49 article-no= start-page=33264 end-page=33275 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mass Production of Graphene Oxide Beyond the Laboratory: Bridging the Gap Between Academic Research and Industry en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mass production of graphene oxide (GO) has garnered significant attention in recent years due to its potential applications in various fields, from materials science to biomedicine. Graphene, known for its unique properties, such as high conductivity and mechanical strength, has been extensively studied. However, traditional production methods such as the exfoliation of graphite with scotch tape are not suitable for large-scale production. This has led to an increased focus on GO as a viable alternative to graphene production. Nonetheless, challenges, including the optimization of oxidation processes, the control of structural uniformity, and the reproducibility of production, have not been solved so far. This review critically examines GO production advancements by analyzing experimental and mechanistic studies to identify significant developments that enable high-yield and reproducible methods suitable for industrial-scale production. Special attention is given to oxidation techniques and postsynthesis purification and storage, with a focus on controlled oxidation to achieve homogeneous and single-layer GO. Through this lens, the review outlines the path forward for the industrialization of GO, aiming to bridge the gap between academic research and industrial production. en-copyright= kn-copyright= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=Graphene oxide kn-keyword=Graphene oxide en-keyword=Graphite kn-keyword=Graphite en-keyword=Chemical oxidation kn-keyword=Chemical oxidation en-keyword=Electrochemical oxidation kn-keyword=Electrochemical oxidation en-keyword=Mass production kn-keyword=Mass production en-keyword=Purification kn-keyword=Purification en-keyword=Optimization kn-keyword=Optimization en-keyword=Industrialization kn-keyword=Industrialization en-keyword=Safety kn-keyword=Safety en-keyword=Stability kn-keyword=Stability END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=28 end-page=36 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=Local Control of Conjunctival Malignant Melanoma by Proton Beam Therapy in a Patient With No Metastasis in Six Years From in Situ to Nodular Lesions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Conjunctival malignant melanoma is extremely rare, with no standard of care established at moment. Here we report a 65-year-old woman, as a hepatitis B virus (HBV) carrier, who presented concurrently a liver mass and lower bulbar conjunctival pigmented lesions in the right eye. Needle liver biopsy and excisional conjunctival biopsy showed hepatocellular carcinoma and conjunctival malignant melanoma in situ, respectively. The priority was given to segmental liver resection for hepatocellular carcinoma after transcatheter arterial chemoembolization. In 1 year, she underwent second and third resection of bulbar conjunctival pigmented lesions, and the pathological examinations constantly showed melanoma in situ. In the course, she showed gradual widening of pigmented lesions to upper bulbar conjunctiva and lower palpebral conjunctiva and lower eyelid. About 2.5 years from the initial visit, the lower eyelid lesion was resected for a genomic DNA-based test of BRAF mutations which turned out to be absent, and then, she began to have intravenous anti-programmed cell death-1 (PD-1), nivolumab every 3 or 4 weeks. She developed iritis in the right eye with conjunctival melanoma as an immune-related adverse event, 3 months after the beginning of nivolumab, and so she used daily topical 0.1% betamethasone eye drops to control the intraocular inflammation. She showed no metastasis in 6 years of follow-up, but later in the course, 5 years from the initial visit, she developed abruptly a non-pigmented nodular lesion on the temporal side of the bulbar conjunctiva along the corneal limbus, accompanied by two pigmented nodular lesions in the upper and lower eyelids in a few months. She thus, underwent proton beam therapy toward the conjunctival melanoma and achieved the successful local control. Proton beam therapy is a treatment option in place of orbital exenteration, and multidisciplinary team collaboration is desirable to achieve better cosmetic and functional outcomes in conjunctival malignant melanoma. 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=OgataTakeshi en-aut-sei=Ogata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WakiTakahiro en-aut-sei=Waki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AdachiTakuya en-aut-sei=Adachi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Regenerative and Reconstructive Medicine (Ophthalmology), Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiology, Proton Beam Center, Tsuyama Chuo Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Proton Beam Center, Tsuyama Chuo Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Dermatology, 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 Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Ocular surface kn-keyword=Ocular surface en-keyword=Conjunctiva kn-keyword=Conjunctiva en-keyword=Malignant melanoma kn-keyword=Malignant melanoma en-keyword=Proton beam therapy kn-keyword=Proton beam therapy en-keyword=Nivolumab kn-keyword=Nivolumab en-keyword=PD-1 inhibitor kn-keyword=PD-1 inhibitor en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=12 article-no= start-page=e0315385 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phase-dependent trends in the prevalence of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) related to long COVID: A criteria-based retrospective study in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
The characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) related to COVID-19 have remained uncertain. To elucidate the clinical trend of ME/CFS induced by long COVID, we examined data for patients who visited our outpatient clinic established in a university hospital during the period from Feb 2021 to July 2023.

Methods
Long COVID patients were classified into two groups, an ME/CFS group and a non-ME/CFS group, based on three diagnostic criteria.

Results
The prevalence of ME/CFS in the long COVID patients was 8.4% (62 of 739 cases; female: 51.6%) and factors related to ME/CFS were severe illness, smoking and alcohol drinking habits, and fewer vaccinations. The frequency of ME/CFS decreased from 23.9% in the Preceding period to 13.7% in the Delta-dominant period and to 3.3% in the Omicron-dominant period. Fatigue and headache were commonly frequent complaints in the ME/CFS group, and the frequency of poor concentration in the ME/CFS group was higher in the Omicron period. Serum ferritin levels were significantly higher in female patients in the ME/CFS group infected in the Preceding period. In the ME/CFS group, the proportion of patients complaining of brain fog significantly increased from 22.2% in the Preceding period to 47.9% in the Delta period and to 81.3% in the Omicron period. The percentage of patients who had received vaccination was lower in the ME/CFS group than the non-ME/CFS group over the study period, whereas there were no differences in the vaccination rate between the groups in each period.

Conclusion
The proportion of long COVID patients who developed ME/CFS strictly diagnosed by three criteria was lower among patients infected in the Omicron phase than among patients infected in the other phases, while the proportion of patients with brain fog inversely increased. Attention should be paid to the variant-dependent trends of ME/CFS triggered by long COVID (300 words). en-copyright= kn-copyright= en-aut-name=MoritaSatoru en-aut-sei=Morita en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HondaHiroyuki en-aut-sei=Honda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SunadaNaruhiko en-aut-sei=Sunada en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakuradaYasue en-aut-sei=Sakurada en-aut-mei=Yasue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsudaYui en-aut-sei=Matsuda en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SoejimaYoshiaki en-aut-sei=Soejima en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UedaKeigo en-aut-sei=Ueda en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=23 article-no= start-page=10342 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Assessing CO2 Reduction Effects Through Decarbonization Scenarios in the Residential and Transportation Sectors: Challenges and Solutions for Japan's Hilly and Mountainous Areas en-subtitle= kn-subtitle= en-abstract= kn-abstract=Depopulation, aging, and regional decline are becoming increasingly serious issues in Japan's hilly and mountainous areas. Focusing on mitigating environmental damage and envisioning a sustainable future for these regions, this study examines the potential for reducing CO2 emissions in the residential and transportation sectors by 2050. Bottom-up simulations were used to estimate CO2 emissions. Subsequently, six decarbonization scenarios were formulated, considering various measures from the perspectives of population distribution and technological progress. Based on these scenarios, this study analyzes changes in future population, energy consumption, and CO2 emissions by 2050. The results of this study show the following. (1) Depopulation and aging problems in these regions are expected to become more severe in the future. It is necessary to take action to promote sustainable regional development. (2) Pursuing decarbonization has a positive impact on enhancing regional sustainability; however, maintaining the intensity of measures at the current level could lead to a reduction of only 40% in CO2 emissions per capita by 2050 compared with 2020. (3) Scenarios that strengthen decarbonization measures could achieve a reduction of over 95% by 2050, indicating that carbon neutrality is attainable. However, this will require implementing measures at a higher intensity, especially in the transportation sector. en-copyright= kn-copyright= en-aut-name=HaoXiyue en-aut-sei=Hao en-aut-mei=Xiyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanChuyue en-aut-sei=Yan en-aut-mei=Chuyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NarumiDaisuke en-aut-sei=Narumi en-aut-mei=Daisuke 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=Department of Socio-Environmental Energy Science, Graduate School of Energy Science, Kyoto University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=decarbonization measures kn-keyword=decarbonization measures en-keyword=CO2 reduction kn-keyword=CO2 reduction en-keyword=residential sector kn-keyword=residential sector en-keyword=transportation sector kn-keyword=transportation sector en-keyword=energy consumption kn-keyword=energy consumption en-keyword=CO2 emissions kn-keyword=CO2 emissions en-keyword=hilly and mountainous areas kn-keyword=hilly and mountainous areas en-keyword=area management kn-keyword=area management END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=23 article-no= start-page=4089 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Frequency and Significance of Body Weight Loss During Immunochemotherapy in Patients with Advanced Non-Small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Limited data are available on the frequency and significance of body weight loss during cancer therapy. This study investigated the frequency of patients who experienced body weight loss during immune checkpoint inhibitor (ICI) plus chemotherapy for advanced non-small cell lung cancer (NSCLC) and the impact of weight loss on treatment outcomes. Methods: Using the clinical data of 370 patients with NSCLC who received a combination of ICI and chemotherapy at 13 institutions, this study investigated the frequency of body weight loss > 5% during treatment and determined the impact of body weight loss on patient outcomes. Results: Of the 370 included patients, 141 (38.1%) lost more than 5% of their body weight during ICI plus chemotherapy (WL group). The 2-month landmark analysis showed that patients who experienced body weight loss of >5% during treatment had worse overall survival (OS) and progression-free survival (PFS) than those who did not (OS 14.0 and 31.1 months in the WL non-WL groups, respectively, p < 0.001; PFS 6.8 and 10.9 months in the WL non-WL groups, respectively, p = 0.002). Furthermore, a negative impact of body weight loss on survival was observed even in those who had obesity (body mass index [BMI] >= 25.0) at the start of therapy (OS 12.8 and 25.4 months in the WL non-WL groups, respectively, p < 0.001; PFS 5.7 and 10.7 months in the WL non-WL groups, respectively, p = 0.038). Conclusions: In conclusion, weight loss of >5% during ICI plus chemotherapy negatively influenced patient outcomes. Further and broader studies should investigate the role of nutritional status, specifically weight change and nutritional support, in responsiveness to ICI plus chemotherapy. en-copyright= kn-copyright= en-aut-name=TaokaMasataka en-aut-sei=Taoka en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraTomoki en-aut-sei=Tamura en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoAkiko en-aut-sei=Sato en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraKayo en-aut-sei=Nakamura en-aut-mei=Kayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaiHaruyuki en-aut-sei=Kawai en-aut-mei=Haruyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IchikawaHirohisa en-aut-sei=Ichikawa en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AndoChihiro en-aut-sei=Ando en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OzeIsao en-aut-sei=Oze en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Internal Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Fukuyama City Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Japanese Red Cross Himeji Hospital kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=12 en-affil=Department of General Internal Medicine 4 , Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=16 en-affil=Division of Cancer Information and Control, Aichi Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=body weight loss kn-keyword=body weight loss en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=chemotherapy kn-keyword=chemotherapy END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=1434800 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of extracting and preventively intervening late-stage older adults who are at high risk for spending high medical costs by using the health check-up system in Japan: a pilot study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: In Japan, the seven diseases (femur fracture, cerebral infarction, chronic renal failure, heart failure, dementia, pneumonia, and chronic obstructive pulmonary disease) are the top causes of inpatient medical costs among the late-stage older adults aged 75 years and over. This pilot study was conducted with the following two objectives; (1) to examine the proportion of risks of onset and severity of seven diseases among the late-stage older adults, and (2) to examine the efficacy of interventions focusing on the prevention of unplanned hospitalization.
Methods: Participants were 45,233 older adults aged 75 and over living in Kure City, Japan. In addition to the government-mandated health checkup items, the Intervention group underwent additional risk screening tests included questionnaires, physical examinations, blood tests, and educational guidance by nurses. The efficacy of the intervention was examined whether there were differences in the number of hospitalizations, the use of emergency and critical care, and the incidence of hemodialysis induction between the Intervention and control groups (Usual Health Checkup group and No Health Checkup group) for the 2 years.
Results: There were 485 participants in the Intervention group, 1,067 in the Usual Health Checkup group, and 43,712 in the No Health Checkup group. As the risks of seven diseases in the Intervention group, the largest proportion of deviations occurred for systolic blood pressure (63.3%), estimated salt intake (60.3%), and low-density lipoprotein cholesterol (51.5%). Estimated glomerular filtration rate deviated in 41.0%, N-terminal pro b-type natriuretic peptide in 37.9%. 7.5% scored <2 points on the Mini-Cog (c), and 9.1% performed the Timed Up and Go test in >12 s. The incidence of hospitalization due to any of the seven diseases was significantly higher in the No Health Checkup group (p < 0.001). There were no differences among the three groups in the use of emergency and critical care or the introduction of hemodialysis.
Conclusion: This study revealed that additional health checkup tests and intervention methods could be prevented hospitalization among the adults of 75 years and older. It is necessary to make health checkups and follow-ups more accessible those are already available within the existing health system in Japan. en-copyright= kn-copyright= en-aut-name=KazawaKana en-aut-sei=Kazawa en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiMadoka en-aut-sei=Kawai en-aut-mei=Madoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriyamaMichiko en-aut-sei=Moriyama en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Nursing Science, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=3 en-affil=Division of Nursing Science, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= en-keyword=older adults kn-keyword=older adults en-keyword=health checkups kn-keyword=health checkups en-keyword=health risk kn-keyword=health risk en-keyword=hospitalization kn-keyword=hospitalization en-keyword=education kn-keyword=education END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue= article-no= start-page=3215 end-page=3220 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina en-subtitle= kn-subtitle= en-abstract= kn-abstract=A new psammaplysin derivative, ceratinadin G (1), was obtained from the Okinawan marine sponge Pseudoceratina sp., and the gross structure was clarified through spectroscopic and spectrometric analyses. The absolute configuration of compound 1 was established by comparing its NMR and ECD data with those of the known psammaplysin derivative, psammaplysin F (2). Ceratinadin G (1) is a rare nitrile containing a cyano group as aminoacetonitrile, and is the first psammaplysin derivative possessing a cyano group. In vitro assays indicated that compound 1 displayed moderate cytotoxicity against L1210 murine leukemia cells and KB epidermoid carcinoma cells. en-copyright= kn-copyright= en-aut-name=KurimotoShin-Ichiro en-aut-sei=Kurimoto en-aut-mei=Shin-Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueKouta en-aut-sei=Inoue en-aut-mei=Kouta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhnoTaito en-aut-sei=Ohno en-aut-mei=Taito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaTakaaki en-aut-sei=Kubota en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Showa Pharmaceutical University kn-affil= affil-num=3 en-affil=Showa Pharmaceutical University kn-affil= affil-num=4 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=ceratinadin kn-keyword=ceratinadin en-keyword=cytotoxicity kn-keyword=cytotoxicity en-keyword=marine sponge kn-keyword=marine sponge en-keyword=psammaplysin kn-keyword=psammaplysin en-keyword=Pseudoceratina sp kn-keyword=Pseudoceratina sp END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=6 article-no= start-page=469 end-page=474 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Treatment of Tenosynovial Giant Cell Tumor of the Cervical Spine with Postoperative Anti-RANKL Antibody (Denosumab) Administration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tenosynovial giant cell tumor (TGCT) is a fibrous histiocytic tumor originating in the synovial membrane. While cervical TGCT may not be considered a common diagnosis preoperatively because it is relatively rare, it has a high recurrence rate and should be considered. Total resection is preferable, but it can be challenging due to the risk of damaging the vertebral artery. Denosumab has shown effectiveness as a postoperative treatment for osteolytic bone lesion. Denosumab administration coupled with close follow-up might offer an effective postoperative treatment option for unresectable TGCT with bone invasion. 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=NagaseTakayuki en-aut-sei=Nagase en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=AyadaYoshiyuki en-aut-sei=Ayada en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OdaYoshinao en-aut-sei=Oda en-aut-mei=Yoshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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 Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of 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 Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=tenosynovial giant cell tumor kn-keyword=tenosynovial giant cell tumor en-keyword=bone tumor kn-keyword=bone tumor en-keyword=spine kn-keyword=spine END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=29419 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ADAR1 could be a potential diagnostic target for intrauterine infection patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intrauterine infection (IUI) is mainly an ascending infection in which vaginal and cervical pathogens ascend to the uterus and can affect the fetus. Until now, there is still no effective diagnostic biomarker for IUI, such as chorioamnionitis (CAM) and funisitis (FUN). Deoxyribonucleic acid (DNA)/Ribonucleic acid (RNA) editing molecules such as apolipoprotein-B mRNA-editing complex (APOBEC) 3 families and Adenosine deaminase family acting on RNA (ADAR)1 were examined in chorioamniotic membranes and umbilical cord of 83 patient samples. Furthermore, Ureaplasma parvum induced ADAR1 was investigated in human HTR-8/SVneo EVT cell line. ADAR1 had a significantly higher area under the curve (AUC) (0.721 and 0.745) than other APOBEC3s or cytokines in CAM and FUN patients. In vitro, ureaplasma parvum was demonstrated to activate ADAR1 (p?=?0.025) and reduce RIG-I, IRF3, IFN-α, and IFN-β expression in EVT cell line (p?=?0.005, p?=?0.010, p? Results: The mouse GSCs, 005, were differentiated into TDECs under hypoxic conditions, and TDECs had endothelial cell characteristics independent of the vascular endothelial growth factor (VEGF) pathway. In vivo, inhibition of the VEGF pathway had no anti-tumor effect and increased the percentage of TDECs in the 005 mouse model. Novel anti-angiogenic drugs for glioblastoma were evaluated using a tube formation assay and a drug repositioning strategy with existing blood-brain barrier permeable drugs. Drug screening revealed that the antidepressant sertraline inhibited tube formation of TDECs. Sertraline was administered to differentiated TDECs in vitro and 005 mouse models in vivo to evaluate genetic changes by RNA-Seq and tumor regression effects by immunohistochemistry and MRI. Sertraline reduced Lama4 and Ang2 expressions of TDEC, which play an important role in non-VEGF-mediated angiogenesis in tumors. The combination of a VEGF receptor inhibitor axitinib, and sertraline improved survival and reduced tumor growth in the 005 mouse model.
Conclusion: Collectively, our findings showed the diversity of tumor vascular endothelial cells across VEGF and non-VEGF pathways led to anti-angiogenic resistance. The combination of axitinib and sertraline can represent an effective anti-angiogenic therapy for glioblastoma with safe, low cost, and fast availability. en-copyright= kn-copyright= en-aut-name=TsuboiNobushige en-aut-sei=Tsuboi en-aut-mei=Nobushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UnedaAtsuhito en-aut-sei=Uneda en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=MatsumotoYuji en-aut-sei=Matsumoto en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=FujiiKentaro en-aut-sei=Fujii en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuiHideki en-aut-sei=Matsui en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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 Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Neutron Therapy Research Center, Okayama University 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=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=10 en-affil=Department of Neurosurgery, Hamamatsu University School of Medicine kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= en-keyword=anti-angiogenic therapy kn-keyword=anti-angiogenic therapy en-keyword=antidepressant sertraline kn-keyword=antidepressant sertraline en-keyword=drug repositioning kn-keyword=drug repositioning en-keyword=glioblastoma kn-keyword=glioblastoma en-keyword=tumor derived endothelial cells kn-keyword=tumor derived endothelial cells END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=22 article-no= start-page=7382 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microdetection of Nucleocapsid Proteins via Terahertz Chemical Microscope Using Aptamers en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several methods have been employed, including the detection of viral ribonucleic acid (RNA), nucleocapsid (N) proteins, spike proteins, and antibodies. RNA detection, primarily through polymerase chain reaction tests, targets the viral genetic material, whereas antigen tests detect N and spike proteins to identify active infections. In addition, antibody tests are performed to measure the immune response, indicating previous exposure or vaccination. Here, we used the developed terahertz chemical microscope (TCM) to detect different concentrations of N protein in solution by immobilizing aptamers on a semiconductor substrate (sensing plate) and demonstrated that the terahertz amplitude varies as the concentration of N proteins increases, exhibiting a highly linear relationship with a coefficient of determination (R2 = 0.9881), indicating that a quantitative measurement of N proteins is achieved. By optimizing the reaction conditions, we confirmed that the amplitude of the terahertz wave was independent of the solution volume. Consequently, trace amounts (0.5 μL) of the N protein were successfully detected, and the detection process only took 10 min. Therefore, this study is expected to develop a rapid and sensitive method for the detection and observation of the SARS-CoV-2 virus at a microdetection level. It is anticipated that this research will significantly contribute to reducing the spread of novel infectious diseases in the future. en-copyright= kn-copyright= en-aut-name=DingXue en-aut-sei=Ding en-aut-mei=Xue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurakamiMana en-aut-sei=Murakami en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangJin en-aut-sei=Wang en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KiwaToshihiko en-aut-sei=Kiwa en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hospital kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=terahertz chemical microscope kn-keyword=terahertz chemical microscope en-keyword=aptamers kn-keyword=aptamers en-keyword=N protein kn-keyword=N protein en-keyword=microdetection kn-keyword=microdetection END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page=1468230 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Perspectives of traditional herbal medicines in treating retinitis pigmentosa en-subtitle= kn-subtitle= en-abstract= kn-abstract=Medicinal plants, also known as herbs, have been discovered and utilized in traditional medical practice since prehistoric times. Medicinal plants have been proven rich in thousands of natural products that hold great potential for the development of new drugs. Previously, we reviewed the types of Chinese traditional medicines that a Tang Dynasty monk Jianzhen (Japanese: Ganjin) brought to Japan from China in 742. This article aims to review the origin of Kampo (Japanese traditional medicine), and to present the overview of neurodegenerative diseases and retinitis pigmentosa as well as medicinal plants in some depth. Through the study of medical history of the origin of Kampo, we found that herbs medicines contain many neuroprotective ingredients. It provides us a new perspective on extracting neuroprotective components from herbs medicines to treat neurodegenerative diseases. Retinitis pigmentosa (one of the ophthalmic neurodegenerative diseases) is an incurable blinding disease and has become a popular research direction in global ophthalmology. To date, treatments for retinitis pigmentosa are very limited worldwide. Therefore, we intend to integrate the knowledge and skills from different disciplines, such as medical science, pharmaceutical science and plant science, to take a new therapeutic approach to treat neurodegenerative diseases. In the future, we will use specific active ingredients extracted from medicinal plants to treat retinitis pigmentosa. By exploring the potent bioactive ingredients present in medicinal plants, a valuable opportunity will be offered to uncover novel approaches for the development of drugs which target for retinitis pigmentosa. en-copyright= kn-copyright= en-aut-name=LiuShihui en-aut-sei=Liu en-aut-mei=Shihui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuoChie en-aut-sei=Matsuo en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeTakumi en-aut-sei=Abe en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChenJinghua en-aut-sei=Chen en-aut-mei=Jinghua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SunChi en-aut-sei=Sun en-aut-mei=Chi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhaoQing en-aut-sei=Zhao en-aut-mei=Qing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, 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=Department of Ophthalmology, University of Florida, College of Medicine kn-affil= affil-num=6 en-affil=Department of Ophthalmology and Visual Sciences, Washington University in St. Louis kn-affil= affil-num=7 en-affil=National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= en-keyword=retinitis pigmentosa kn-keyword=retinitis pigmentosa en-keyword=ophthalmology kn-keyword=ophthalmology en-keyword=botany kn-keyword=botany en-keyword=pharmacology kn-keyword=pharmacology en-keyword=medical history kn-keyword=medical history en-keyword=compound kn-keyword=compound en-keyword=drug discovery kn-keyword=drug discovery en-keyword=degenerative diseases kn-keyword=degenerative diseases END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=1920〜30年代の佐藤春夫の文学活動における中国観―中国文学理解の影響の研究― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=QULan en-aut-sei=QU en-aut-mei=Lan kn-aut-name=曲嵐 kn-aut-sei=曲 kn-aut-mei=嵐 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil=岡山大学大学院社会文化科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=線維化を伴う膵がん微小環境の立体培養法による新規in vitroモデルの構築と解析 kn-title=Establishment and Analysis of Novel In Vitro 3D Cell Culture Models of the Fibrotic Tumor Microenvironment in Pancreatic Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TANAKAHiroyoshi en-aut-sei=TANAKA en-aut-mei=Hiroyoshi kn-aut-name=田中啓祥 kn-aut-sei=田中 kn-aut-mei=啓祥 aut-affil-num=1 ORCID= affil-num=1 en-affil=Okayama University kn-affil=岡山大学大学院 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ジェネリック医薬品の効率的開発に資するヒト経口投与後血漿中濃度推移予測システムDissolution-Absorption Prediction (DAP) workflowの構築 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ONISHIMotoki en-aut-sei=ONISHI en-aut-mei=Motoki kn-aut-name=大西元樹 kn-aut-sei=大西 kn-aut-mei=元樹 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ラットモデルにおけるくも膜下出血発症後急性期における脳波抑制は早期脳損傷の重要なマーカーである kn-title=Power suppression in EEG after the onset of SAH is a significant marker of early brain injury in rat models en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TAKASUGIYuji en-aut-sei=TAKASUGI en-aut-mei=Yuji kn-aut-name=杉祐二 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