start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=10 article-no= start-page=2373 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241017 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development and Characterization of a Three-Dimensional Organotypic In Vitro Oral Cancer Model with Four Co-Cultured Cell Types, Including Patient-Derived Cancer-Associated Fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Cancer organoids have emerged as a valuable tool of three-dimensional (3D) cell cultures to investigate tumor heterogeneity and predict tumor behavior and treatment response. We developed a 3D organotypic culture model of oral squamous cell carcinoma (OSCC) to recapitulate the tumor?stromal interface by co-culturing four cell types, including patient-derived cancer-associated fibroblasts (PD-CAFs). Methods: A stainless-steel ring was used twice to create the horizontal positioning of the cancer stroma (adjoining normal oral mucosa connective tissue) and the OSCC layer (surrounding normal oral mucosa epithelial layer). Combined with a structured bi-layered model of the epithelial component and the underlying stroma, this protocol enabled us to construct four distinct portions mimicking the oral cancer tissue arising in the oral mucosa. Results: In this model, ƒ¿-smooth muscle actin-positive PD-CAFs were localized in close proximity to the OSCC layer, suggesting a crosstalk between them. Furthermore, a linear laminin-ƒÁ2 expression was lacking at the interface between the OSCC layer and the underlying stromal layer, indicating the loss of the basement membrane-like structure. Conclusions: Since the specific 3D architecture and polarity mimicking oral cancer in vivo provides a more accurate milieu of the tumor microenvironment (TME), it could be crucial in elucidating oral cancer TME. en-copyright= kn-copyright= en-aut-name=AizawaYuka en-aut-sei=Aizawa en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagaKenta en-aut-sei=Haga en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshibaNagako en-aut-sei=Yoshiba en-aut-mei=Nagako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YortchanWitsanu en-aut-sei=Yortchan en-aut-mei=Witsanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakadaSho en-aut-sei=Takada en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaRintaro en-aut-sei=Tanaka en-aut-mei=Rintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaitoEriko en-aut-sei=Naito en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Ab?Tatsuya en-aut-sei=Ab? en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaruyamaSatoshi en-aut-sei=Maruyama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamazakiManabu en-aut-sei=Yamazaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanumaJun-ichi en-aut-sei=Tanuma en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TomiharaKei en-aut-sei=Tomihara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TogoShinsaku en-aut-sei=Togo en-aut-mei=Shinsaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IzumiKenji en-aut-sei=Izumi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=2 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=3 en-affil=Department of Oral Health and Welfare, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=4 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=5 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=6 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=7 en-affil=Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=8 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=9 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=10 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=11 en-affil=Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=12 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=13 en-affil=Division of Oral and Maxillofacial Surgery, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Graduate School of Medicine, Juntendo University kn-affil= affil-num=15 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=oral cancer kn-keyword=oral cancer en-keyword=cancer-associated fibroblasts kn-keyword=cancer-associated fibroblasts en-keyword=oral mucosa kn-keyword=oral mucosa en-keyword=patient-derived kn-keyword=patient-derived en-keyword=organotypic culture kn-keyword=organotypic culture en-keyword=3D in vitro model kn-keyword=3D in vitro model en-keyword=polarity kn-keyword=polarity END start-ver=1.4 cd-journal=joma no-vol=156 cd-vols= no-issue=2 article-no= start-page=473 end-page=479.e1 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dried blood spot proteome identifies subclinical interferon signature in neonates with type I interferonopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Type I interferonopathy is characterized by aberrant upregulation of type I interferon signaling. The mRNA interferon signature is a useful marker for activation of the interferon pathway and for diagnosis of type I interferonopathy; however, early diagnosis is challenging.
Objective: This study sought to identify the proteomic interferon signature in dried blood spot (DBS) samples. The aim was to evaluate the usefulness of the interferon signature for neonatal screening and to gain insight into presymptomatic state of neonates with inborn errors of immunity (IEIs).
Methods: DBS samples from healthy newborns/adults, patients with type I interferonopathy or other IEIs as well as from neonates with viral infections, including some samples obtained during the presymptomatic neonatal period, were examined by nontargeted proteome analyses. Expression of interferon-stimulated genes (ISGs) was evaluated and a DBS-interferon signature was defined. Differential expression/pathway analysis was also performed.
Results: The ISG products IFIT5, ISG15, and OAS2 were detected. Expression of IFIT5 and ISG15 was upregulated significantly in individuals with type I interferonopathy. We defined the sum of the z scores for these as the DBS-interferon signature, and found that patients with IEIs other than type I interferonopathy, such as chronic granulomatous disease (CGD), also showed significant elevation. Additionally, neonatal samples of type I interferonopathy and CGD patients showed high interferon signatures. Pathway analysis of neonatal CGD samples revealed upregulation of systemic lupus erythematosus?like pathways.
Conclusion: Upregulation of the interferon pathway exists already at birth?not only in neonates with type I interferonopathy but also in other IEIs, including CGD. en-copyright= kn-copyright= en-aut-name=NihiraHiroshi en-aut-sei=Nihira en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaDaisuke en-aut-sei=Nakajima en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IzawaKazushi en-aut-sei=Izawa en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawashimaYusuke en-aut-sei=Kawashima en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShibataHirofumi en-aut-sei=Shibata en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KonnoRyo en-aut-sei=Konno en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashiguchiMotoko en-aut-sei=Higashiguchi en-aut-mei=Motoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoTakayuki en-aut-sei=Miyamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nishitani-IsaMasahiko en-aut-sei=Nishitani-Isa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiejimaEitaro en-aut-sei=Hiejima en-aut-mei=Eitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HondaYoshitaka en-aut-sei=Honda en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsubayashiTadashi en-aut-sei=Matsubayashi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiharaTakashi en-aut-sei=Ishihara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwataNaomi en-aut-sei=Iwata en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OhwadaYoko en-aut-sei=Ohwada en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TomotakiSeiichi en-aut-sei=Tomotaki en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawaiMasahiko en-aut-sei=Kawai en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MurakamiKosaku en-aut-sei=Murakami en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhnishiHidenori en-aut-sei=Ohnishi en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IshimuraMasataka en-aut-sei=Ishimura en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OkadaSatoshi en-aut-sei=Okada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YamashitaMotoi en-aut-sei=Yamashita en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MorioTomohiro en-aut-sei=Morio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HoshinoAkihiro en-aut-sei=Hoshino en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KaneganeHirokazu en-aut-sei=Kanegane en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ImaiKohsuke en-aut-sei=Imai en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakamuraYasuko en-aut-sei=Nakamura en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NonoyamaShigeaki en-aut-sei=Nonoyama en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UchiyamaToru en-aut-sei=Uchiyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=OnoderaMasafumi en-aut-sei=Onodera en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=IshikawaTakashi en-aut-sei=Ishikawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawaiToshinao en-aut-sei=Kawai en-aut-mei=Toshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=TakitaJunko en-aut-sei=Takita en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NishikomoriRyuta en-aut-sei=Nishikomori en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OharaOsamu en-aut-sei=Ohara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=YasumiTakahiro en-aut-sei=Yasumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= affil-num=1 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=7 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Seirei Hamamatsu General Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Nara Medical University kn-affil= affil-num=14 en-affil=Department of Pediatrics, Okayama University kn-affil= affil-num=15 en-affil=Department of Infection and Immunology, Aichi Childrenfs Health and Medical Center kn-affil= affil-num=16 en-affil=Department of Pediatrics, Dokkyo Medical University School of Medicine kn-affil= affil-num=17 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neonatology, Kyoto University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Pediatrics, Gifu University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=22 en-affil=Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences kn-affil= affil-num=23 en-affil=Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=24 en-affil=Laboratory of Immunology and Molecular Medicine, Advanced Research Initiative, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=25 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=26 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=27 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=28 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=29 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=30 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=31 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=32 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=33 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=34 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=35 en-affil=Department of Pediatrics and Child Health, Kurume University School of Medicine kn-affil= affil-num=36 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=37 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= en-keyword=Inborn errors of immunity kn-keyword=Inborn errors of immunity en-keyword=interferonopathy kn-keyword=interferonopathy en-keyword=signature kn-keyword=signature en-keyword=proteome kn-keyword=proteome en-keyword=dried blood spot kn-keyword=dried blood spot en-keyword=CGD kn-keyword=CGD en-keyword=WAS kn-keyword=WAS en-keyword=newborn kn-keyword=newborn en-keyword=neonate kn-keyword=neonate END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=roaf042 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recommendations for the treatment of juvenile idiopathic arthritis with oligoarthritis or polyarthritis from the 2024 update of the Japan College of Rheumatology Clinical Practice Guidelines for the management of rheumatoid arthritis including juvenile idiopathic arthritis with oligoarthritis or polyarthritis ? secondary publication en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To conduct systematic reviews (SRs) and develop clinical practice guidelines (CPGs) for managing juvenile idiopathic arthritis (JIA) with oligoarthritis or polyarthritis.
Methods: The Grading of Recommendations, Assessment, Development, and Evaluation methodology was employed to carry out SRs and formulate the CPGs. An expert panel, including patients, paediatric and nonpaediatric rheumatologists, guideline specialists, and patient representatives, used the Delphi method to discuss and agree on the recommendations.
Results: Six clinical questions (CQs) on the efficacy and safety of medical treatments were evaluated. These included CQ1 on methotrexate (MTX), CQ2 on non-MTX conventional synthetic disease-modifying antirheumatic drugs, CQ3 on glucocorticoids, CQ4 on tumour necrosis factor inhibitors, CQ5 on interleukin-6 inhibitors, and CQ6 on Janus kinase inhibitors. Two randomized controlled trials were identified for CQ1, three for CQ2, two for CQ3, eight for CQ4, two for CQ5, and two for CQ6. Based on these evaluations, three strong and three conditional recommendations were established. The CPGs have been endorsed by the Japan College of Rheumatology and the Pediatric Rheumatology Association of Japan.
Conclusions: The SRs provided the necessary evidence to develop the CPGs, which are intended to guide not only paediatric but also nonpaediatric rheumatologists, caregivers, patients, and their families in treatment decision-making. en-copyright= kn-copyright= en-aut-name=MiyamaeTakako en-aut-sei=Miyamae en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkamotoNami en-aut-sei=Okamoto en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueYuzaburo en-aut-sei=Inoue en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaTomohiro en-aut-sei=Kubota en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EbatoTakasuke en-aut-sei=Ebato en-aut-mei=Takasuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IrabuHitoshi en-aut-sei=Irabu en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamedaHideto en-aut-sei=Kameda en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanekoYuko en-aut-sei=Kaneko en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuboHiroshi en-aut-sei=Kubo en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MitsunagaKanako en-aut-sei=Mitsunaga en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MoriMasaaki en-aut-sei=Mori en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakajimaAyako en-aut-sei=Nakajima en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimuraKenichi en-aut-sei=Nishimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OhkuboNaoaki en-aut-sei=Ohkubo en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SatoTomomi en-aut-sei=Sato en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SugitaYuko en-aut-sei=Sugita en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakanashiSatoshi en-aut-sei=Takanashi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaTakayuki en-aut-sei=Tanaka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UmebayashiHiroaki en-aut-sei=Umebayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamanishiShingo en-aut-sei=Yamanishi en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FusamaMie en-aut-sei=Fusama en-aut-mei=Mie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HirataShintaro en-aut-sei=Hirata en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KishimotoMitsumasa en-aut-sei=Kishimoto en-aut-mei=Mitsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KohnoMasataka en-aut-sei=Kohno en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KojimaMasayo en-aut-sei=Kojima en-aut-mei=Masayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KojimaToshihisa en-aut-sei=Kojima en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MorinobuAkio en-aut-sei=Morinobu en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=SugiharaTakahiko en-aut-sei=Sugihara en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=TanakaEiichi en-aut-sei=Tanaka en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=YajimaNobuyuki en-aut-sei=Yajima en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=YanaiRyo en-aut-sei=Yanai en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawahitoYutaka en-aut-sei=Kawahito en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HarigaiMasayoshi en-aut-sei=Harigai en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Department of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Womenfs Medical University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety kn-affil= affil-num=3 en-affil=Department of General Medical Science, Graduate School of Medicine, Chiba University kn-affil= affil-num=4 en-affil=Department of Pediatrics, Kagoshima Prefectural Satsunan Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kitasato University kn-affil= affil-num=6 en-affil=Department of Pediatrics and Development Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=7 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University kn-affil= affil-num=8 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=10 en-affil=Department of Allergy and Rheumatology, Chiba Children's Hospital kn-affil= affil-num=11 en-affil=Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University kn-affil= affil-num=12 en-affil=Center for Rheumatic Diseases, Mie University Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Yokohama City University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Iizuka Hospital kn-affil= affil-num=15 en-affil=Clinical Education Center For Physicians, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Pediatrics, School of Medicine, Osaka Medical and Pharmaceutical University kn-affil= affil-num=17 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Department of Pediatrics, Japanese Red Cross Otsu Hospital kn-affil= affil-num=19 en-affil=Department of Rheumatology and Infectious Diseases, Miyagi Childrenfs Hospital kn-affil= affil-num=20 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Pediatrics, Nippon Medical School kn-affil= affil-num=22 en-affil=Health Sciences Department of Nursing, Kansai University of International Studies kn-affil= affil-num=23 en-affil=Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital kn-affil= affil-num=24 en-affil=Department of Nephrology and Rheumatology, Kyorin University School of Medicine kn-affil= affil-num=25 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=26 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=27 en-affil=Department of Orthopedic Surgery, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=28 en-affil=Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=29 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine kn-affil= affil-num=30 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= affil-num=31 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=32 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=33 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=34 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= en-keyword=Clinical practice guidelines kn-keyword=Clinical practice guidelines en-keyword=baricitinib kn-keyword=baricitinib en-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) kn-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) en-keyword=juvenile idiopathic arthritis kn-keyword=juvenile idiopathic arthritis en-keyword=systematic review kn-keyword=systematic review END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue= article-no= start-page=244 end-page=256 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Postnatal expression of Cat-315-positive perineuronal nets in the SAMP10 mouse primary somatosensory cortex en-subtitle= kn-subtitle= en-abstract= kn-abstract=Perineuronal nets (PNNs) form at the end of the critical period of plasticity in the mouse primary somatosensory cortex. PNNs are said to have functions that control neuroplasticity and provide neuroprotection. However, it is not clear which molecules in PNNs have these functions. We have previously reported that Cat-315-positive molecules were not expressed in the PNNs of the senescence-accelerated model (SAM)P10 strain model mice at 12 months of age. To confirm whether the loss of Cat-315-positive molecules occurred early in life in SAMP10 mice, we examined Cat-315-positive PNNs in the primary somatosensory cortex during postnatal development. This research helps to elucidate the function of PNNs and the mechanism of cognitive decline associated with ageing. To confirm whether Cat-315-positive PNNs changed in an age-dependent manner in SAMP10 mice, we examined the primary somatosensory cortex at 21, 28, and 56 days after birth. We compared these results with those of senescence-accelerated mouse-resistant (SAMR) mice. In SAMP10 mice, Cat-315-positive PNNs were expressed in the primary somatosensory cortex early after birth, but their expression was significantly lower than that in SAMR1 mice. Many other molecules that calibrated the PNN were unchanged between SAMP10 and SAMR1 mice. This study revealed that the expression of the Cat-315 epitope was decreased in the primary somatosensory cortex of SAMP10 mice during postnatal development. SAMP10 mice have had histological abnormalities in their brains since early life. Furthermore, using SAMP10 will be useful in elucidating the mechanism of age-related abnormalities in brain function as well as in elucidating the function and structure of PNNs. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=Ageing kn-keyword=Ageing en-keyword=Brain function kn-keyword=Brain function en-keyword=Neuroplasticity kn-keyword=Neuroplasticity en-keyword=Neuroprotection kn-keyword=Neuroprotection en-keyword=Cognitive decline kn-keyword=Cognitive decline END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Age-related behavioural abnormalities in C57BL/6.KOR?Apoe shl mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spontaneously hyperlipidaemic (Apoeshl) mice were discovered in 1999 as mice lacking apolipoprotein E (ApoE) owing to a mutation in the Apoe gene. However, age-related behavioural changes in commercially available Apoeshl mice have not yet been clarified. The behavioural abnormalities of ApoE-deficient mice, which are genetically modified mice artificially deficient in ApoE, have been investigated in detail, and it has been reported that they can serve as a model of Alzheimerfs disease (AD). To understand whether Apoeshl mice can also serve as a murine model of AD, it is necessary to investigate age-related behavioural abnormalities in Apoeshl mice. In this study, we conducted a series of behavioural experiments on 7- and 11-month-old Apoeshl mice to investigate the behavioural abnormalities associated with ageing in Apoeshl mice. In this study, 7-month-old Apoeshl mice showed decreased body weight and grip strength compared to age-matched wild-type mice. In the open field test, 7-month-old Apoeshl mice showed increased anxiety-like behaviour compared to wild-type mice, whereas 11-month-old Apoeshl mice showed decreased anxiety-like behaviour. Moreover, Apoeshl mice aged 7 and 11 months had increased serum cholesterol levels. These results indicate that the behaviour of Apoeshl mice changes with age. However, 11-month-old Apoeshl mice did not show a decline in cognitive function or memory ability similar to murine models of AD. Our findings indicate that Apoeshl mice can be used to investigate the function of ApoE in the central nervous system. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiYu en-aut-sei=Takahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriSachiko en-aut-sei=Mori en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitanoEriko en-aut-sei=Kitano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyazakiTetsuji en-aut-sei=Miyazaki en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=age kn-keyword=age en-keyword=apolipoprotein kn-keyword=apolipoprotein en-keyword=behavioural test kn-keyword=behavioural test en-keyword=central nervous system kn-keyword=central nervous system en-keyword=mouse kn-keyword=mouse END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=12 article-no= start-page=1399 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association Between Chewing Status and Steatotic Liver Disease in Japanese People Aged ?50 Years: A Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: In this longitudinal study, the relationship between chewing status and steatotic liver disease (SLD) was examined in 3775 people aged ?50 years who underwent medical checkups at Junpukai Health Maintenance Center in Okayama, Japan. Methods: Participants without SLD at the time of a baseline survey in 2018 were followed until 2022. Chewing status was assessed by a self-administered questionnaire. The presence or absence of SLD was ascertained from the medical records of Junpukai Health Maintenance Center. Results: A total of 541 participants (14%) were diagnosed as having a poor chewing status at baseline. Furthermore, 318 (8%) participants were newly diagnosed with SLD at follow-up. In multivariate logistic regression analyses, the presence or absence of SLD was found to be associated with the following characteristics at baseline: sex (male: odds ratio [ORs] = 1.806; 95% confidence interval [CIs]: 1.399?2.351), age (ORs = 0.969; 95% CIs: 0.948?0.991), body mass index (?25.0 kg/m2; ORs = 1.934; 95% CIs: 1.467?2.549), diastolic blood pressure (ORs = 1.017; 95% CIs: 1.002?1.032), and chewing status (poor: ORs = 1.472; 95% CIs: 1.087?1.994). Conclusions: The results indicate that a poor chewing status was associated with SLD development after 4 years. Aggressively recommending dental visits to participants with poor chewing status may not only improve their ability to chew well but may also reduce the incidence of SLD. en-copyright= kn-copyright= en-aut-name=IwaiKomei en-aut-sei=Iwai en-aut-mei=Komei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=AzumaTetsuji en-aut-sei=Azuma en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YonenagaTakatoshi en-aut-sei=Yonenaga en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TabataKoichiro en-aut-sei=Tabata en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Community Oral Health, School of Dentistry, Asahi University kn-affil= affil-num=2 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Community Oral Health, School of Dentistry, Asahi University kn-affil= affil-num=4 en-affil=Department of Community Oral Health, School of Dentistry, Asahi University kn-affil= affil-num=5 en-affil=Department of Community Oral Health, School of Dentistry, Asahi University kn-affil= affil-num=6 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Community Oral Health, School of Dentistry, Asahi University kn-affil= en-keyword=oral health kn-keyword=oral health en-keyword=liver diseases kn-keyword=liver diseases en-keyword=longitudinal studies kn-keyword=longitudinal studies en-keyword=mastication kn-keyword=mastication en-keyword=physical examination kn-keyword=physical examination en-keyword=surveys and questionnaires kn-keyword=surveys and questionnaires END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=4 article-no= start-page=292 end-page=296 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=Computed tomography findings of idiopathic multicentric Castleman disease subtypes en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study retrospectively evaluated the computed tomography (CT) findings of idiopathic multicentric Castleman disease (iMCD) at a single center and compared the CT findings of iMCD-TAFRO with those of iMCD-non-TAFRO. CT images obtained within 30 days before diagnostic confirmation were reviewed for 20 patients with iMCD (8 men and 12 women, mean age 52.8 } 12.3 years, range 25?74 years). Twelve patients were diagnosed with iMCD-TAFRO, five with iMCD-idiopathic plasmacytic lymphadenopathy, and three with iMCD-not otherwise specified. CT images revealed anasarca and lymphadenopathy in all 20 patients. The iMCD-TAFRO group showed significantly higher frequencies of ascites (100% vs. 37.5%, P = 0.004), gallbladder wall edema (75.0% vs. 12.5%, P = 0.020), periportal collar (91.7% vs. 25.0%, P = 0.004), and anterior mediastinal lesions (non-mass-forming infiltrative lesions) (66.7% vs. 12.5%, P = 0.028). Para-aortic edema tended to be more frequent in patients with the iMCD-TAFRO group (83.3% vs. 37.5%, P = 0.062), while the absence of anterior mediastinal lesions tended to be more frequent in the iMCD-non-TAFRO group (16.7% vs. 62.5%, P = 0.062). These CT findings may have clinical implications for improving the accuracy and speed of iMCD diagnosis and differentiating iMCD-TAFRO from other subtypes. en-copyright= kn-copyright= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwakiNoriko en-aut-sei=Iwaki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaKatsuhide en-aut-sei=Kojima en-aut-mei=Katsuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=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 Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, National Cancer Center Hospital kn-affil= affil-num=6 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Radiological Technology, Faculty of Health 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 Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=idiopathic multicentric Castleman disease kn-keyword=idiopathic multicentric Castleman disease en-keyword=TAFRO syndrome kn-keyword=TAFRO syndrome en-keyword=computed tomography kn-keyword=computed tomography END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=3 article-no= start-page=e70167 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Occupational therapist]guided exercise increased white blood cell and neutrophil counts during clozapine treatment: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Moderate exercise increases white blood cells and neutrophils. However, there are no reports on the relationship between exercise intensity and these cells. We observed a patient taking clozapine whose white blood cell and neutrophil counts were borderline. Supervised exercise therapy with an occupational therapist stabilized these counts.
Case Presentation: A 50-year-old woman with treatment-resistant schizophrenia was prescribed clozapine. By Day 63, the clozapine dosage had been increased to 450?mg/day. Additionally, she was advised to perform a 30-min walking exercise program 1 h before blood tests. Exercise therapy supervised by an occupational therapist was performed eight times, and self-training was performed five times. Exercise intensity was monitored using the Borg Scale for subjective evaluation and the Karvonen formula for objective evaluation. Supervised exercise therapy with an occupational therapist resulted in greater increases on the Borg Scale and Karvonen formula than did self-training. It also induced increases in white blood cells and neutrophils. Her psychiatric symptoms improved, and she was discharged on Day 71. A blood test taken after discharge revealed that her white blood cell and neutrophil counts were within the normal range and she continued to take clozapine for 2 years. She has since been able to enjoy a calm and relaxed life at home.
Conclusion: Exercise involving subjective and objective evaluation by an occupational therapist effectively increased white blood cells and neutrophils during clozapine treatment. Supervised exercise therapy by an occupational therapist is important when self-exercise is insufficient for continuing clozapine treatment. en-copyright= kn-copyright= en-aut-name=HinotsuKenji en-aut-sei=Hinotsu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KawaiHiroki en-aut-sei=Kawai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhyaYoshio en-aut-sei=Ohya en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YokodeAkiyoshi en-aut-sei=Yokode en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaTakahiro en-aut-sei=Asada en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkahisaYuko en-aut-sei=Okahisa en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neuropsychiatry, 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 Hospital kn-affil= affil-num=7 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=clozapine kn-keyword=clozapine en-keyword=exercise kn-keyword=exercise en-keyword=leukopenia kn-keyword=leukopenia en-keyword=neutropenia kn-keyword=neutropenia en-keyword=occupational therapist kn-keyword=occupational therapist END start-ver=1.4 cd-journal=joma no-vol=2892 cd-vols= no-issue= article-no= start-page=012002 end-page= 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=Crystal Grain Rotation during Tensile Test of Polycrystalline Pure Titanium Thin Sheet Based on Surface Height and Crystal Orientation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thin sheets and wires of polycrystalline pure titanium are important materials for various devices used in electrical, mechanical, dental, and medical fields. Since pure titanium shows strong anisotropy in elastic and plastic deformation, and the individual grains comprising a polycrystalline body have different orientations and geometries, inhomogeneous deformation always occurs on the microscopic scale. This inhomogeneity is more significant in thin films than in bulk materials. It is therefore important to investigate the inhomogeneous deformation of pure titanium thin sheets to ensure the reliability of various titanium devices. In this study, thin-sheet specimens made of polycrystalline pure titanium were subjected to tensile testing. Inhomogeneous deformation was evaluated on the basis of two kinds of crystal grain rotations based on surface height and crystal orientation. The results under elastic and plastic tensile conditions were compared. en-copyright= kn-copyright= en-aut-name=TadaNaoya en-aut-sei=Tada en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhashiHiroaki en-aut-sei=Ohashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UemoriTakeshi en-aut-sei=Uemori en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoJunji en-aut-sei=Sakamoto en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=9 article-no= start-page=4310 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=The Possibility of Plasma Membrane Transporters as Drug Targets in Oral Cancers en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plasma membrane transporters are increasingly recognized as potential drug targets for oral cancer, particularly oral squamous cell carcinoma (OSCC). These transporters play crucial roles in cancer cell metabolism, drug resistance, and the tumor microenvironment, making them attractive targets for therapeutic intervention. Among the two main families of plasma membrane transporters, ATP-binding cassette (ABC) transporters have long been known to be involved in drug efflux and contribute to chemoresistance in cancer cells. On the other hand, solute carriers (SLCs) are also a family of transporters that facilitate the transport of various substrates, including nutrients and drugs, and have recently been shown to contribute to cancer chemosensitivity, metabolism, and proliferation. SLC transporters have been identified as potential cancer biomarkers and therapeutic targets, and their expression profiles suggest that they could be utilized in precision oncology approaches. We summarize previous reports on the expression and role of ABC and SLC transporters in oral cancer and discuss their potential as therapeutic targets. en-copyright= kn-copyright= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimadaKatsumitsu en-aut-sei=Shimada en-aut-mei=Katsumitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= affil-num=1 en-affil=Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology kn-affil= affil-num=2 en-affil=Department of Clinical Phathophysiology, Matsumoto Dental University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=SLC transporter kn-keyword=SLC transporter en-keyword=ABC transporter kn-keyword=ABC transporter en-keyword=oral cancer kn-keyword=oral cancer en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1561628 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250321 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Histidine-rich glycoprotein inhibits TNF-ƒ¿?induced tube formation in human vascular endothelial cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Tumor necrosis factor-ƒ¿ (TNF-ƒ¿)-induced angiogenesis plays a critical role in tumor progression and metastasis, making it an important therapeutic target in cancer treatment. Suppressing angiogenesis can effectively limit tumor growth and metastasis. However, despite advancements in understanding angiogenic pathways, effective strategies to inhibit TNF-ƒ¿-mediated angiogenesis remain limited.
Methods: This study investigates the antiangiogenic effects of histidine-rich glycoprotein (HRG), a multifunctional plasma protein with potent antiangiogenic properties, on TNF-ƒ¿-stimulated human endothelial cells (EA.hy926). Tube formation assays were performed to assess angiogenesis, and gene/protein expression analyses were conducted to evaluate HRGfs effects on integrins ƒ¿V and ƒÀ8. The role of nuclear factor erythroid 2-related factor 2 (NRF2) in HRG-mediated antiangiogenic activity was also examined through nuclear translocation assays and NRF2 activation studies.
Results: At physiological concentrations, HRG effectively suppressed TNF-ƒ¿-induced tube formation in vitro and downregulated TNF-ƒ¿-induced expression of integrins ƒ¿V and ƒÀ8 at both the mRNA and protein levels. HRG treatment promoted NRF2 nuclear translocation in a time-dependent manner. Furthermore, activation of NRF2 significantly reduced TNF-ƒ¿-induced tube formation and integrin expression, suggesting that NRF2 plays a key role in HRG-mediated antiangiogenic effects.
Discussion and Conclusion: Our findings indicate that HRG suppresses TNF-ƒ¿-induced angiogenesis by promoting NRF2 nuclear translocation and transcriptional activation, which in turn inhibits integrin ƒ¿V and ƒÀ8 expression. Given the essential role of angiogenesis in tumor progression, HRGfs ability to regulate this process presents a promising therapeutic strategy for cancer treatment. en-copyright= kn-copyright= en-aut-name=HatipogluOmer Faruk en-aut-sei=Hatipoglu en-aut-mei=Omer Faruk kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishinakaTakashi en-aut-sei=Nishinaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaykasliKursat Oguz en-aut-sei=Yaykasli en-aut-mei=Kursat Oguz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriShuji en-aut-sei=Mori en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeMasahiro en-aut-sei=Watanabe en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToyomuraTakao en-aut-sei=Toyomura en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakahashiHideo en-aut-sei=Takahashi en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pharmacology, Kindai University Faculty of Medicine kn-affil= affil-num=2 en-affil=Department of Pharmacology, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Internal Medicine 3?Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-N?rnberg (FAU) and Universit?tsklinikum Erlangen kn-affil= affil-num=4 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=5 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=6 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=7 en-affil=Department of Translational Research and Dug Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmacology, Kindai University Faculty of Medicine kn-affil= affil-num=10 en-affil=Department of Pharmacology, Kindai University Faculty of Medicine kn-affil= en-keyword=histidine-rich glycoprotein kn-keyword=histidine-rich glycoprotein en-keyword=tumor necrosis factor-ƒ¿ kn-keyword=tumor necrosis factor-ƒ¿ en-keyword=integrin kn-keyword=integrin en-keyword=tube formation kn-keyword=tube formation en-keyword=angiogenesis kn-keyword=angiogenesis en-keyword=factor erythroid 2-related factor 2 kn-keyword=factor erythroid 2-related factor 2 END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=S1 article-no= start-page=7 end-page=12 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=Basic biology is not just gfor the birdsh: how avian studies have informed us about vertebrate reproduction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Avian reproductive physiology has been studied for centuries, largely because of the importance of birds as food animals. It is likely that the ubiquity and ease of access to domesticated chickens led to them being used in some of the first experiments on transplantation of endocrine structures?in this case, the testes. Since then, study of seasonal changes in reproductive physiology (photoperiodism) in different orders of bird species has led to advances in the understanding of endocrine regulation of reproductive physiology and behavior. These include mechanisms of adult neuroplasticity, sexual selection, sperm competition, stress physiology, and circadian physiology. Here, we focus mainly on the discovery in birds of a neuropeptide named gonadotropin-inhibitory hormone that mostly has inhibitory effects on reproduction. This hormone has since been shown to exist in all mammals studied to date, including humans (it is known as RFamide-related peptide in mammals). We discuss the history and implications of avian studies on gonadotropin-inhibitory hormone/RFamide-related peptide for human reproductive biology. en-copyright= kn-copyright= en-aut-name=BentleyGeorge E. en-aut-sei=Bentley en-aut-mei=George E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= affil-num=1 en-affil=Department of Integrative Biology and Helen Wills Neuroscience Institute, University of California at Berkeley kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=GnRH kn-keyword=GnRH en-keyword=GnIH kn-keyword=GnIH en-keyword=RFamide kn-keyword=RFamide END start-ver=1.4 cd-journal=joma no-vol=1863 cd-vols= no-issue= article-no= start-page=149752 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spearmint extract Neumentix downregulates amyloid-ƒÀ accumulation by promoting phagocytosis in APP23 mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=In recent years, many researchers have focused on natural compounds that can effectively delay symptoms of Alzheimerfs disease (AD). The spearmint extract Neumentix, which is rich in phenolic compounds, has been shown to reduce inflammatory responses and oxidative stress in mice. However, the effect of Neumentix on AD has not been thoroughly studied. In this study, APP23 transgenic female and male mice were administered Neumentix orally from 4 to 18 months of age at a dosage of 2.65 g/kg/day (containing 0.41 g/kg/day of rosmarinic acid). The impact was evaluated by behavioral tests and histological analyses and compared with APP23 mice to which Neumentix was not administered. The results showed that Neumentix administration increased the survival rate of APP23 mice and effectively reduced AƒÀ accumulation by enhancing its phagocytosis by microglial cells. These findings suggest that Neumentix is a potential natural nutritional treatment for improving the progression of AD. en-copyright= kn-copyright= en-aut-name=HuXinran en-aut-sei=Hu en-aut-mei=Xinran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=BianYuting en-aut-sei=Bian en-aut-mei=Yuting 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=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=6 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=7 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=National Center Hospital, National Center of Neurology and Psychiatry kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Alzheimer's disease kn-keyword=Alzheimer's disease en-keyword=Amyloid-beta kn-keyword=Amyloid-beta en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Neumentix kn-keyword=Neumentix en-keyword=Phagocytosis kn-keyword=Phagocytosis en-keyword=Survival rate kn-keyword=Survival rate END start-ver=1.4 cd-journal=joma no-vol=89 cd-vols= no-issue=8 article-no= start-page=1217 end-page=1226 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microbial biotransformation of proteins into amino acids in unpolished Thai and polished Japanese rice varieties cultivated with distinct industrial strains of koji mold en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported the cultivation of industrial koji mold strains to produce unpolished Thai-colored rice kojis. These kojis, along with those made from unpolished Thai white rice and polished Japanese white rice, showed increased polyphenol content after cultivation, with the highest levels observed in unpolished Thai-colored rice kojis. In this study, an increase in both proteinogenic and non-proteinogenic amino acid contents, particularly ƒÁ-aminobutyric acid (GABA) content, was observed in both unpolished Thai and polished Japanese rice kojis, suggesting the ability of koji mold in the biotransformation of proteins. This increase was almost comparable even when using different rice varieties; in contrast, it varied depending on the koji mold strain used. The observed increase in both polyphenol and functional amino acid contents, especially GABA content, highlights the potential of unpolished Thai and polished Japanese rice kojis, particularly unpolished Thai-colored rice koji, as multifunctional materials, benefiting from polyphenol and amino acid functionalities. en-copyright= kn-copyright= en-aut-name=JitpakdeeJirayu en-aut-sei=Jitpakdee en-aut-mei=Jirayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoKazunari en-aut-sei=Ito en-aut-mei=Kazunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaninoYuka en-aut-sei=Tanino en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeuchiHayato en-aut-sei=Takeuchi en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamashitaHideyuki en-aut-sei=Yamashita en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakagawaTakuro en-aut-sei=Nakagawa en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NitodaTeruhiko en-aut-sei=Nitoda en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanzakiHiroshi en-aut-sei=Kanzaki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Industrial Technology Center of Okayama Prefecture kn-affil= affil-num=3 en-affil=Industrial Technology Center of Okayama Prefecture kn-affil= affil-num=4 en-affil=Industrial Technology Center of Okayama Prefecture kn-affil= affil-num=5 en-affil=Higuchi Matsunosuke Shoten Co., Ltd. kn-affil= affil-num=6 en-affil=Higuchi Matsunosuke Shoten Co., Ltd. kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Amino acid kn-keyword=Amino acid en-keyword=GABA kn-keyword=GABA en-keyword=koji mold kn-keyword=koji mold en-keyword=rice koji kn-keyword=rice koji en-keyword=Thai-colored rice kn-keyword=Thai-colored rice END start-ver=1.4 cd-journal=joma no-vol=98 cd-vols= no-issue=6 article-no= start-page=uoaf044 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Redox-potential-controlled intermolecular [2 + 2] cycloaddition of styrenes for the regio- and diastereoselective synthesis of multisubstituted halogenocyclobutanes en-subtitle= kn-subtitle= en-abstract= kn-abstract=The redox potential is an important factor for controlling the outcome of photoredox catalysis. Particularly, the selective oxidation of substrates and the control over the reactions are challenging when using photoredox catalysts that have high excited-state reduction potentials. In this study, a redox-potential-controlled intermolecular [2 + 2] cycloaddition of styrenes using a thioxanthylium organophotoredox (TXT) catalyst has been developed. This TXT catalyst selectively oxidizes ƒÀ-halogenostyrenes and smoothly promotes the subsequent intermolecular [2 + 2] cycloadditions to give multisubstituted halogenocyclobutanes with excellent regio- and diastereoselectivity, which has not been effectively achieved by the hitherto reported representative photoredox catalysts. The synthesized halogenocyclobutanes exhibit interesting free radical scavenging activity. The present reaction contributes to the field of redox-potential-controlled electron transfer chemistry. en-copyright= kn-copyright= en-aut-name=MizutaniAsuka en-aut-sei=Mizutani en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoMomo en-aut-sei=Kondo en-aut-mei=Momo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItakuraShoko en-aut-sei=Itakura en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakamuraHiroyoshi en-aut-sei=Takamura en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoshinoYujiro en-aut-sei=Hoshino en-aut-mei=Yujiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishikawaMakiya en-aut-sei=Nishikawa en-aut-mei=Makiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KusamoriKosuke en-aut-sei=Kusamori en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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=Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science kn-affil= affil-num=3 en-affil=Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science 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 Environment and Information Sciences, Yokohama National University kn-affil= affil-num=6 en-affil=Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science 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=Laboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of Science kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=redox potential kn-keyword=redox potential en-keyword=photoredox catalysis kn-keyword=photoredox catalysis en-keyword=[2 + 2] cycloaddition kn-keyword=[2 + 2] cycloaddition 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=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The stress?strain behavior of poly(methyl acrylate) microparticle-based polymers determined via optical microscopy en-subtitle= kn-subtitle= en-abstract= kn-abstract=The structural integrity of microparticle-based films is maintained through interpenetration of the superficial polymer chains of the microparticles that physically crosslink neighboring microparticles. This structural feature is fundamentally different from those of conventional polymers prepared by solvent casting or bulk polymerization. To understand the mechanical properties of such microparticle-based films, it is necessary to investigate the behavior of their constituent particles. However, methods are still being developed to evaluate microscale structural changes in microparticle-based films during the stretching process leading to film fracture. In this study, we propose a method that combines a stretching stage with optical microscopy to investigate the changes in particle morphology and its positional relationship with surrounding particles during uniaxial tensile tests on microparticle-based films. In a film consisting of cross-linked poly(methyl acrylate) microparticles, the deformation of the particles deviated from affine deformation due to the cross-linked structure. However, the deformation of a group of several (local) particles was confirmed to be location-dependent and larger than that of each particle forming the film. The method established here can be used to contribute to the design of tough microparticle-based films. en-copyright= kn-copyright= en-aut-name=NishizawaYuichiro en-aut-sei=Nishizawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawamuraYuto en-aut-sei=Kawamura en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasakiYuma en-aut-sei=Sasaki en-aut-mei=Yuma 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=raduate School of Textile Science & Technology, Shinshu 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= END start-ver=1.4 cd-journal=joma no-vol=140 cd-vols= no-issue= article-no= start-page=745 end-page=776 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=Advances in filler-crosslinked membranes for hydrogen fuel cells in sustainable energy generation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fuel cell membranes can be used in various ways to achieve zero-emission transport and energy systems, which offer a promising way to power production due to their higher efficiency compared to the internal combustion engine and the eco-environment. Perfluoro sulfonic acid membranes used for proton exchange membranes (PEMs) have certain drawbacks, like higher fuel permeability and expense, lower mechanical and chemical durability, and proton conductivity under low humidity and above 80 ‹C temperature. Researchers have drawn their attention to the production of polymer electrolyte membranes with higher proton conductivity, thermal and chemical resilience, maximum power density, lower fuel permeability, and lower expense. For sustainable clean energy generation, a review covering the most useful features of advanced material-associated membranes would be of great benefit to all interested communities. This paper endeavors to explore several types of novel inorganic fillers and crosslinking agents, which have been incorporated into membrane matrices to design the desired properties for an advanced fuel cell system. Membrane parameters such as proton conductivity, the ability of H2 transport, and the stability of the membrane are described. Research directions for developing fuel cell membranes are addressed based on several challenges suggested. The technological advancement of nanostructured materials for fuel cell applications is believed to significantly promote the future clean energy generation technology in practice. en-copyright= kn-copyright= en-aut-name=IslamAminul en-aut-sei=Islam en-aut-mei=Aminul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShahriarMamun en-aut-sei=Shahriar en-aut-mei=Mamun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IslamMd. Tarekul en-aut-sei=Islam en-aut-mei=Md. Tarekul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TeoSiow Hwa en-aut-sei=Teo en-aut-mei=Siow Hwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KhanM. Azizur R. en-aut-sei=Khan en-aut-mei=M. Azizur R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Taufiq-YapYun Hin en-aut-sei=Taufiq-Yap en-aut-mei=Yun Hin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MohantaSuman C. en-aut-sei=Mohanta en-aut-mei=Suman C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=RehanAriyan Islam en-aut-sei=Rehan en-aut-mei=Ariyan Islam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=RaseeAdiba Islam en-aut-sei=Rasee en-aut-mei=Adiba Islam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KubraKhadiza Tul en-aut-sei=Kubra en-aut-mei=Khadiza Tul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HasanMd. Munjur en-aut-sei=Hasan en-aut-mei=Md. Munjur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SalmanMd. Shad en-aut-sei=Salman en-aut-mei=Md. Shad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WaliullahR.M. en-aut-sei=Waliullah en-aut-mei=R.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HasanMd. Nazmul en-aut-sei=Hasan en-aut-mei=Md. Nazmul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SheikhMd. Chanmiya en-aut-sei=Sheikh en-aut-mei=Md. Chanmiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UchidaTetsuya en-aut-sei=Uchida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AwualMrs Eti en-aut-sei=Awual en-aut-mei=Mrs Eti kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HossainMohammed Sohrab en-aut-sei=Hossain en-aut-mei=Mohammed Sohrab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ZnadHussein en-aut-sei=Znad en-aut-mei=Hussein kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=AwualMd. Rabiul en-aut-sei=Awual en-aut-mei=Md. Rabiul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Petroleum and Mining Engineering, Jashore University of Science and Technology kn-affil= affil-num=2 en-affil=Department of Petroleum and Mining Engineering, Jashore University of Science and Technology kn-affil= affil-num=3 en-affil=Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology kn-affil= affil-num=4 en-affil=Industrial Chemistry Program, Faculty of Science and Natural Resources, Universiti Malaysia Sabah kn-affil= affil-num=5 en-affil=Department of Chemistry, Jashore University of Science and Technology kn-affil= affil-num=6 en-affil=Catalysis Science and Technology Research Centre, Faculty of Science, Universiti Putra Malaysia kn-affil= affil-num=7 en-affil=Department of Chemistry, Jashore University of Science and Technology kn-affil= affil-num=8 en-affil=Department of Chemistry, School of Science, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=10 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=11 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=12 en-affil=Institute for Chemical Research, Kyoto University kn-affil= affil-num=13 en-affil=Institute for Chemical Research, Kyoto University kn-affil= affil-num=14 en-affil=Department of Chemistry, School of Science, The University of Tokyo kn-affil= affil-num=15 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=16 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=17 en-affil=Institute for Chemical Research, Kyoto University kn-affil= affil-num=18 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=19 en-affil=Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University kn-affil= affil-num=20 en-affil=Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University kn-affil= en-keyword=Advanced materials kn-keyword=Advanced materials en-keyword=Fuel cell kn-keyword=Fuel cell en-keyword=Hydrogen gas generation kn-keyword=Hydrogen gas generation en-keyword=Proton exchange membrane kn-keyword=Proton exchange membrane en-keyword=Polymer kn-keyword=Polymer END start-ver=1.4 cd-journal=joma no-vol=101 cd-vols= no-issue= article-no= start-page=173 end-page=211 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=Next frontier in photocatalytic hydrogen production through CdS heterojunctions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photocatalytic hydrogen (H?) generation via solar-powered water splitting represents a sustainable solution to the global energy crisis. Cadmium sulfide (CdS) has emerged as a promising semiconductor photocatalyst due to its tunable bandgap, high physicochemical stability, cost-effectiveness, and widespread availability. This review systematically examines recent advancements in CdS-based heterojunctions, categorized into CdS-metal (Schottky), CdS-semiconductor (p-n, Z-scheme, S-scheme), and CdS-carbon heterojunctions. Various strategies employed to enhance photocatalytic efficiency and stability are discussed, including band structure engineering, surface modification, and the incorporation of crosslinked architectures. A critical evaluation of the underlying photocatalytic mechanisms highlights recent efforts to improve charge separation and photostability under operational conditions. This review highlights the challenges and opportunities in advancing CdS-based photocatalysts and provides a direction for future research. The insights presented aim to accelerate the development of efficient and durable CdS-based photocatalysts for sustainable H? production. en-copyright= kn-copyright= en-aut-name=IslamAminul en-aut-sei=Islam en-aut-mei=Aminul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MalekAbdul en-aut-sei=Malek en-aut-mei=Abdul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IslamMd. Tarekul en-aut-sei=Islam en-aut-mei=Md. Tarekul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NipaFarzana Yeasmin en-aut-sei=Nipa en-aut-mei=Farzana Yeasmin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RaihanObayed en-aut-sei=Raihan en-aut-mei=Obayed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MahmudHasan en-aut-sei=Mahmud en-aut-mei=Hasan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UddinMd. Elias en-aut-sei=Uddin en-aut-mei=Md. Elias kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IbrahimMohd Lokman en-aut-sei=Ibrahim en-aut-mei=Mohd Lokman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Abdulkareem-AlsultanG. en-aut-sei=Abdulkareem-Alsultan en-aut-mei=G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MondalAlam Hossain en-aut-sei=Mondal en-aut-mei=Alam Hossain kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HasanMd. Munjur en-aut-sei=Hasan en-aut-mei=Md. Munjur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SalmanMd. Shad en-aut-sei=Salman en-aut-mei=Md. Shad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KubraKhadiza Tul en-aut-sei=Kubra en-aut-mei=Khadiza Tul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HasanMd. Nazmul en-aut-sei=Hasan en-aut-mei=Md. Nazmul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SheikhMd. Chanmiya en-aut-sei=Sheikh en-aut-mei=Md. Chanmiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UchidaTetsuya en-aut-sei=Uchida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=RaseeAdiba Islam en-aut-sei=Rasee en-aut-mei=Adiba Islam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=RehanAriyan Islam en-aut-sei=Rehan en-aut-mei=Ariyan Islam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AwualMrs Eti en-aut-sei=Awual en-aut-mei=Mrs Eti kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HossainMohammed Sohrab en-aut-sei=Hossain en-aut-mei=Mohammed Sohrab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=WaliullahR.M. en-aut-sei=Waliullah en-aut-mei=R.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=AwualMd. Rabiul en-aut-sei=Awual en-aut-mei=Md. Rabiul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Petroleum and Mining Engineering, Jashore University of Science and Technology kn-affil= affil-num=2 en-affil=Department of Petroleum and Mining Engineering, Jashore University of Science and Technology kn-affil= affil-num=3 en-affil=Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology kn-affil= affil-num=4 en-affil=Department of Petroleum and Mining Engineering, Jashore University of Science and Technology kn-affil= affil-num=5 en-affil=Department of Pharmaceutical Sciences, College of Health Sciences and Pharmacy, Chicago State University kn-affil= affil-num=6 en-affil=Bangladesh Energy and Power Research Council (BEPRC) kn-affil= affil-num=7 en-affil=Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology kn-affil= affil-num=8 en-affil=School of Chemistry and Environment, Faculty of Applied Sciences, Universiti Teknologi MARA kn-affil= affil-num=9 en-affil=Catalysis Science and Technology Research Centre, Faculty of Science, Universiti Putra Malaysia kn-affil= affil-num=10 en-affil=USAID - Bangladesh Advancing Development and Growth through Energy (BADGE) Project, Tetra Tech kn-affil= affil-num=11 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=12 en-affil=Institute for Chemical Research, Kyoto University kn-affil= affil-num=13 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=14 en-affil=Department of Chemistry, School of Science, The University of Tokyo kn-affil= affil-num=15 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=16 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=17 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=18 en-affil=Department of Chemistry, School of Science, The University of Tokyo kn-affil= affil-num=19 en-affil=Institute for Chemical Research, Kyoto University kn-affil= affil-num=20 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=21 en-affil=Institute for Chemical Research, Kyoto University kn-affil= affil-num=22 en-affil=Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University kn-affil= en-keyword=H2 kn-keyword=H2 en-keyword=Sustainability kn-keyword=Sustainability en-keyword=Photocatalytic kn-keyword=Photocatalytic en-keyword=Photo-stability kn-keyword=Photo-stability en-keyword=Heterojunction kn-keyword=Heterojunction en-keyword=CdS kn-keyword=CdS END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=1 article-no= start-page=144 end-page=156 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241109 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lymphadenectomy and chemotherapy are effective treatments for patients with 2023 international federation of gynecology and obstetrics stage IIC-high risk endometrial cancer in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background In early-stage endometrial cancer (EC), the treatment of aggressive histological subtypes (endometrioid carcinoma grade 3, serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, mixed carcinoma, and carcinosarcoma) is controversial. We aimed to investigate the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IC and stage IIC EC according to the 2023 classification.
Methods We retrospectively identified patients with FIGO 2023 stage IC, IIC-intermediate risk (IIC-I), and IIC-high risk (IIC-H) EC who underwent adjuvant therapy or observation after surgery at eight medical institutions from 2004 to 2023. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan?Meier estimates and univariate and multivariate analyses.
Results The PFS and OS were significantly worse in patients with FIGO 2023 stage IIC-H EC than in those with FIGO 2023 stage IIC-I EC (PFS: p?=?0.008 and OS: p?=?0.006). According to the FIGO 2023 stage IIC-H classification, lymphadenectomy and chemotherapy resulted in better prognoses regarding both PFS and OS (p? Conclusion Lymphadenectomy and chemotherapy resulted in better prognoses regarding both recurrence and survival in patients with FIGO 2023 stage IIC high-risk EC. en-copyright= kn-copyright= en-aut-name=TaniYoshinori en-aut-sei=Tani en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=YorimitsuMasae en-aut-sei=Yorimitsu en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekiNoriko en-aut-sei=Seki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanishiMie en-aut-sei=Nakanishi en-aut-mei=Mie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItouHironori en-aut-sei=Itou en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimizuMiyuki en-aut-sei=Shimizu en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoDan en-aut-sei=Yamamoto en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakaharaEtsuko en-aut-sei=Takahara en-aut-mei=Etsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Kagawa Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, National Organization Fukuyama Medical Center kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Fukuyama City Hospital kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Endometrial cancer kn-keyword=Endometrial cancer en-keyword=FIGO 2023 kn-keyword=FIGO 2023 en-keyword=Stage IIC high risk kn-keyword=Stage IIC high risk en-keyword=Lymphadenectomy kn-keyword=Lymphadenectomy en-keyword=Chemotherapy kn-keyword=Chemotherapy 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=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=From sewage sludge to agriculture: governmental initiatives, technologies, and sustainable practices in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sewage sludge (SS), an underutilized but valuable resource for agriculture, contains essential nutrients, such as phosphorus. In Japan, where dependence on imported fertilizers is high and global price fluctuations persist, using SS as fertilizer presents a sustainable alternative aligned with circular economy goals. This review analyzes Japanfs current efforts to repurpose SS, focusing on technological developments and key policy initiatives that promote safe and effective application. Selective phosphorus recovery technologies mitigate resource depletion, while holistic approaches, such as composting and carbonization, maximize sludge utilization for agricultural applications. Government-led initiatives, including public awareness campaigns, quality assurance standards and research support, have facilitated the adoption of sludge-based fertilizers. To contextualize Japanfs position, international trends, particularly in the EU, are also examined. These comparisons reveal both common strategies and areas for policy and technological advancement, especially regarding regulation of emerging contaminants. By integrating national case studies with global perspectives, the study offers insights into the economic, environmental, and social benefits of SS reuse, contributing to Japanfs goals of resource self-sufficiency and carbon neutrality, while also informing broader sustainable agriculture transitions worldwide. en-copyright= kn-copyright= en-aut-name=NguyenThu Huong en-aut-sei=Nguyen en-aut-mei=Thu Huong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTaku en-aut-sei=Fujiwara en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaHiromasa en-aut-sei=Yamashita en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TogawaHironori en-aut-sei=Togawa en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyakeHaruo en-aut-sei=Miyake en-aut-mei=Haruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GotoMasako en-aut-sei=Goto en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagareHideaki en-aut-sei=Nagare en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraMasato en-aut-sei=Nakamura en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OritateFumiko en-aut-sei=Oritate en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IharaHirotaka en-aut-sei=Ihara en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaMorihiro en-aut-sei=Maeda en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Engineering, Kyoto University kn-affil= affil-num=2 en-affil=Graduate School of Engineering, Kyoto University kn-affil= affil-num=3 en-affil=Water Supply and Sewerage Department, National Institute for Land and Infrastructure Management kn-affil= affil-num=4 en-affil=Water Supply and Sewerage Department, National Institute for Land and Infrastructure Management kn-affil= affil-num=5 en-affil=R & D Department, Japan Sewage Works Agency kn-affil= affil-num=6 en-affil=1St Research Department, Japan Institute of Wastewater Engineering and Technology 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=Institute for Rural Engineering, NARO kn-affil= affil-num=9 en-affil=Institute for Rural Engineering, NARO kn-affil= affil-num=10 en-affil=Institute for Agro-Environmental Sciences, NARO kn-affil= affil-num=11 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Japan kn-keyword=Japan en-keyword=Sewage sludge kn-keyword=Sewage sludge en-keyword=Agriculture kn-keyword=Agriculture en-keyword=Sludge fertilizers kn-keyword=Sludge fertilizers en-keyword=Governmental initiatives kn-keyword=Governmental initiatives END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=23 article-no= start-page=3243 end-page=3248 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful Treatment for Life Threatening Recurrent Non-traumatic Rectus Sheath Hematoma in a Case with Microscopic Polyangiitis with Rapidly Progressive Glomerulonephritis en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 68-year-old woman was admitted to our hospital because of a rapid progression of renal dysfunction with positive myeloperoxidase antineutrophil cytoplasmic antibody and was diagnosed with rapidly progressive glomerulonephritis associated with microscopic polyangiitis (MPA). Severe right rectus sheath hematoma (RSH) bleeding from the inferior epigastric artery developed after starting hemodialysis, which required 4 transarterial embolizations due to recurrent bleeding. After additional treatment with methylprednisolone pulse therapy and rituximab, no rebleeding occurred. Although the giant hematoma reached the pelvis, it shrank spontaneously without any intervention. Nontraumatic RSH should therefore be considered when treating patients with multiple risk factors. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimotoShiho en-aut-sei=Morimoto en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TerajimaYuya en-aut-sei=Terajima en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkamotoShugo en-aut-sei=Okamoto en-aut-mei=Shugo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=rectus sheath hematoma kn-keyword=rectus sheath hematoma en-keyword=microscopic polyangiitis kn-keyword=microscopic polyangiitis en-keyword=hemodialysis kn-keyword=hemodialysis END start-ver=1.4 cd-journal=joma no-vol=343 cd-vols= no-issue= article-no= start-page=103558 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Progress in silicon-based materials for emerging solar-powered green hydrogen (H2) production en-subtitle= kn-subtitle= en-abstract= kn-abstract=The imperative demand for sustainable and renewable energy solutions has precipitated profound scientific investigations into photocatalysts designed for the processes of water splitting and hydrogen fuel generation. The abundance, low toxicity, high conductivity, and cost-effectiveness of silicon-based compounds make them attractive candidates for hydrogen production, driving ongoing research and technological advancements. Developing an effective synthesis method that is simple, economically feasible, and environmentally friendly is crucial for the widespread implementation of silicon-based heterojunctions for sustainable hydrogen production. Balancing the performance benefits with the economic and environmental considerations is a key challenge in the development of these systems. The specific performance of each catalyst type can vary depending on the synthesis method, surface modifications, catalyst loading, and reaction conditions. The confluence of high crystallinity, reduced oxygen concentration, and calcination temperature within the silicon nanoparticle has significantly contributed to its noteworthy hydrogen evolution rate. This review provides an up-to-date evaluation of Si-based photocatalysts, summarizing recent developments, guiding future research directions, and identifying areas that require further investigation. By combining theoretical insights and experimental findings, this review offers a comprehensive understanding of Si-based photocatalysts for water splitting. Through a comprehensive analysis, it aims to elucidate existing knowledge gaps and inspire future research directions towards optimized photocatalytic performance and scalability, ultimately contributing to the realization of sustainable hydrogen generation. en-copyright= kn-copyright= en-aut-name=IslamAminul en-aut-sei=Islam en-aut-mei=Aminul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IslamMd. Tarekul en-aut-sei=Islam en-aut-mei=Md. Tarekul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TeoSiow Hwa en-aut-sei=Teo en-aut-mei=Siow Hwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MahmudHasan en-aut-sei=Mahmud en-aut-mei=Hasan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SwarazA.M. en-aut-sei=Swaraz en-aut-mei=A.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RehanAriyan Islam en-aut-sei=Rehan en-aut-mei=Ariyan Islam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=RaseeAdiba Islam en-aut-sei=Rasee en-aut-mei=Adiba Islam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KubraKhadiza Tul en-aut-sei=Kubra en-aut-mei=Khadiza Tul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HasanMd. Munjur en-aut-sei=Hasan en-aut-mei=Md. Munjur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SalmanMd. Shad en-aut-sei=Salman en-aut-mei=Md. Shad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WaliullahR.M. en-aut-sei=Waliullah en-aut-mei=R.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HasanMd. Nazmul en-aut-sei=Hasan en-aut-mei=Md. Nazmul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SheikhMd. Chanmiya en-aut-sei=Sheikh en-aut-mei=Md. Chanmiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UchidaTetsuya en-aut-sei=Uchida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AwualMrs Eti en-aut-sei=Awual en-aut-mei=Mrs Eti kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HossainMohammed Sohrab en-aut-sei=Hossain en-aut-mei=Mohammed Sohrab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ZnadHussein en-aut-sei=Znad en-aut-mei=Hussein kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AwualMd. Rabiul en-aut-sei=Awual en-aut-mei=Md. Rabiul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Petroleum and Mining Engineering, Jashore University of Science and Technology kn-affil= affil-num=2 en-affil=Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology kn-affil= affil-num=3 en-affil=Industrial Chemistry Program, Faculty of Science and Natural Resources, Universiti Malaysia Sabah kn-affil= affil-num=4 en-affil=Bangladesh Energy and Power Research Council (BEPRC) kn-affil= affil-num=5 en-affil=Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology kn-affil= affil-num=6 en-affil=Department of Chemistry, School of Science, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=8 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=9 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=10 en-affil=Institute for Chemical Research, Kyoto University kn-affil= affil-num=11 en-affil=Institute for Chemical Research, Kyoto University kn-affil= affil-num=12 en-affil=Department of Chemistry, School of Science, The University of Tokyo kn-affil= affil-num=13 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=14 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=15 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=16 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=17 en-affil=Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University kn-affil= affil-num=18 en-affil=Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University kn-affil= en-keyword=Silicon-based materials kn-keyword=Silicon-based materials en-keyword=Water splitting kn-keyword=Water splitting en-keyword=Hydrogen kn-keyword=Hydrogen en-keyword=Sustainable kn-keyword=Sustainable en-keyword=Clean and renewable energy kn-keyword=Clean and renewable energy END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=2 article-no= start-page=71 end-page=81 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=Study on the Removal Technology of Trichloramine from Drinking Water Using Ultraviolet Light en-subtitle= kn-subtitle= en-abstract= kn-abstract=Trichloramine (NCl3) is an inorganic chloramine that causes a pungent chlorine-like odor, and it is difficult to remove its precursors (nitrogen organic compounds and/or ammonia) completely from water. Powdered activated carbon, ozonation, and UV treatment have been applied for decomposing NCl3, but free chlorine was also decomposed. So, it is necessary to develop a technique that can selectively control NCl3 without losing free chlorine. UV light-emitting diodes (265, 280, and 300?nm) and plasma emission UV sheet (347 } 52?nm, hereafter 350?nm) were compared to find the optimal wavelengths that decompose NCl3 but not free chlorine. As a result, 90.6, 96.7, 92.5, and 77.8% of NCl3 were removed at 265, 280, 300 (3,600?mJ/cm2), and 350?nm (14,400?mJ/cm2), respectively. On the other hand, free chlorine at neutral pH (hypochlorous acid is dominant) and slightly alkaline pH (hypochlorite ion is dominant) was not decomposed at 350?nm, but at other wavelengths (i.e., 265, 280, and 300?nm) the removals were more than 64%. Therefore, UV radiation at 350?nm can be candidates to remove NCl3 while maintaining free chlorine. However, this method requires high input energy, and further study is needed for evaluating the practical applicability of this method by considering optimal reactor design. en-copyright= kn-copyright= en-aut-name=HashiguchiAyumi en-aut-sei=Hashiguchi en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaShiho en-aut-sei=Yoshida en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EchigoShinya en-aut-sei=Echigo en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakanamiRyohei en-aut-sei=Takanami en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagareHideaki en-aut-sei=Nagare en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Shimane University kn-affil= affil-num=3 en-affil=Graduate School of Global Environmental Studies, Kyoto University kn-affil= affil-num=4 en-affil=Faculty of Design Technology, Osaka Sangyo University kn-affil= affil-num=5 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=trichloramine kn-keyword=trichloramine en-keyword=disinfection byproducts kn-keyword=disinfection byproducts en-keyword=drinking water kn-keyword=drinking water en-keyword=ultraviolet light kn-keyword=ultraviolet light END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=1 article-no= start-page=43 end-page=53 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=Fan-Shaped Pneumatic Soft Actuator that Can Operate Bending Motion for Ankle-Joint Rehabilitation Device en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, owing to declining birthrates and an aging population, patients and the elderly requiring rehabilitation are not getting enough physical activity. In addressing this issue, devices for rehabilitating them have been researched and developed. However, rehabilitation devices are almost exclusively used for patients who can get up, rather than those who are bedridden. In this study, we aim to develop a rehabilitation device that can provide passive exercise for bedridden patients. The ankle joint was selected as the target joint because the patients who have undergone surgery for cerebrovascular disease remain bedridden, and early recovery in the acute stage is highly desirable. We proposed and tested a fan-shaped pneumatic soft actuator (FPSA) that can expand and bend stably at angles when supply pressure is applied as an actuator for a rehabilitation device to encourage patient exercise. However, the previous FPSAfs movement deviates from the arch of the foot owing to increased supply pressure. In the ideal case, FPSA should push the arch of the foot in an arc motion. This study proposes and tests the FPSA that can operate a bending motion to provide passive exercise to the ankle joint using tensile springs and a winding mechanism powered by a servo motor. The proposed FPSA has a significant advantage of exhibiting no hysteresis in its pressure-displacement characteristics. The configuration and static analytical model of the improved FPSA are described. en-copyright= kn-copyright= en-aut-name=ShimookaSo en-aut-sei=Shimooka en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoyaHirosato en-aut-sei=Yokoya en-aut-mei=Hirosato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaMasanori en-aut-sei=Hamada en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShiomiShun en-aut-sei=Shiomi en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UeharaTakenori en-aut-sei=Uehara en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, 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=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, NHO Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=fan-shaped pneumatic soft actuator kn-keyword=fan-shaped pneumatic soft actuator en-keyword=ankle-joint rehabilitation device kn-keyword=ankle-joint rehabilitation device en-keyword=hysteresis kn-keyword=hysteresis en-keyword=range of motion kn-keyword=range of motion END start-ver=1.4 cd-journal=joma no-vol=329 cd-vols= no-issue=1 article-no= start-page=L183 end-page=L196 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Activated factor X inhibition ameliorates NF-ƒÈB-IL-6-mediated perivascular inflammation and pulmonary hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract=Activated factor X (FXa) induces inflammatory response and cell proliferation in various cell types via activation of proteinase-activated receptor-1 (PAR1) and/or PAR2. We thus aimed to investigate the impact of FXa on the development of pulmonary arterial hypertension (PAH) and the mechanisms involved. The effects of edoxaban, a selective FXa inhibitor, on hemodynamic, right ventricular (RV) hypertrophy, and vascular remodeling were evaluated in a monocrotaline (MCT)-exposed pulmonary hypertension (PH) rat model. At 21 days after a single subcutaneous injection of MCT of 60 mg/kg, right ventricular systolic pressure (RVSP) and total pulmonary vascular resistance index (TPRI) were elevated concomitant with the increased plasma FXa and lung interleukin-6 (IL-6) mRNA. Daily administration of edoxaban (10 mg/kg/day, by gavage) starting from the day of MCT injection for 21 days ameliorated RVSP, TPRI, RV hypertrophy, pulmonary vascular remodeling, and macrophage accumulation. Edoxaban reduced nuclear factor-kappa B (NF-ƒÈB) activity and IL-6 mRNA level in the lungs of MCT-exposed rats. mRNA levels of FXa, PAR1, and PAR2 in cultured pulmonary arterial smooth muscle cells (PASMCs) isolated from patients with PAH were higher than those seen in normal PASMCs. FXa stimulation increased cell proliferation and mRNA level of IL-6 in normal PASMCs, both of which were blunted by edoxaban and PAR1 antagonist. Moreover, FXa stimulation activated extracellularly regulated kinases 1/2 in a PAR1-dependent manner. Inhibition of FXa ameliorates NF-ƒÈB-IL-6-mediated perivascular inflammation, pulmonary vascular remodeling, and the development of PH in MCT-exposed rats, suggesting that FXa may be a potential target for the treatment of PAH.
NEW & NOTEWORTHY This study demonstrated that chronic treatment with activated factor X (FXa) inhibitor ameliorated NF-ƒÈB-IL-6-mediated perivascular inflammation in a rat model with pulmonary arterial hypertension, which is associated with elevated FXa activity. FXa may act on pulmonary arterial smooth muscle cells, inducing cell proliferation and inflammatory response via upregulated PAR1, thereby contributing to pulmonary vascular remodeling. Understanding the patient-specific pathophysiology is a prerequisite for applying FXa-targeted therapy to the treatment of pulmonary arterial hypertension. en-copyright= kn-copyright= en-aut-name=ImakiireSatomi en-aut-sei=Imakiire en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuroKeiji en-aut-sei=Kimuro en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaKeimei en-aut-sei=Yoshida en-aut-mei=Keimei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasakiKohei en-aut-sei=Masaki en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IzumiRyo en-aut-sei=Izumi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImabayashiMisaki en-aut-sei=Imabayashi en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeTakanori en-aut-sei=Watanabe en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshikawaTomohito en-aut-sei=Ishikawa en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HosokawaKazuya en-aut-sei=Hosokawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsushimaShouji en-aut-sei=Matsushima en-aut-mei=Shouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HashimotoToru en-aut-sei=Hashimoto en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShinoharaKeisuke en-aut-sei=Shinohara en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatsukiShunsuke en-aut-sei=Katsuki en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatobaTetsuya en-aut-sei=Matoba en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=HiranoKatsuya en-aut-sei=Hirano en-aut-mei=Katsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsutsuiHiroyuki en-aut-sei=Tsutsui en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=AbeKohtaro en-aut-sei=Abe en-aut-mei=Kohtaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=15 en-affil=Department of Cardiovascular Medicine, Okayama University kn-affil= affil-num=16 en-affil=Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= affil-num=18 en-affil=Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University kn-affil= en-keyword=factor Xa kn-keyword=factor Xa en-keyword=IL-6 kn-keyword=IL-6 en-keyword=proteinase-activated receptor kn-keyword=proteinase-activated receptor en-keyword=pulmonary arterial hypertension kn-keyword=pulmonary arterial hypertension en-keyword=pulmonary hypertension kn-keyword=pulmonary hypertension END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=30648 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the maturation of the cardiomyocytes. This study aimed to improve the differentiation and subsequent maturation of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunocytochemistry, transmission electron microscopy, calcium imaging and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and MYL2) in both groups, with higher protein expression in the stretch group. Additionally, structural maturation of iPS-CMs in the stretch group was notably better than in the control group. A significant increase in the contractility and calcium cycle of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturation of iPS-CMs co-cultured with HGF. en-copyright= kn-copyright= en-aut-name=WangMengxue en-aut-sei=Wang en-aut-mei=Mengxue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IdeiHarumi en-aut-sei=Idei en-aut-mei=Harumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangChen en-aut-sei=Wang en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiangYin en-aut-sei=Liang en-aut-mei=Yin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiuYun en-aut-sei=Liu en-aut-mei=Yun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsudaYusuke en-aut-sei=Matsuda en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nursing, School of Life and Health Sciences, HuZhou College kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Human induced pluripotent stem cell kn-keyword=Human induced pluripotent stem cell en-keyword=Cardiomyocyte kn-keyword=Cardiomyocyte en-keyword=Human gingival fibroblast kn-keyword=Human gingival fibroblast en-keyword=Mechanical stretching kn-keyword=Mechanical stretching END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=2 article-no= start-page=282 end-page=289 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240917 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of a novel central venous access port for direct catheter insertion without a peel-away sheath en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose This study retrospectively evaluated the feasibility and safety of implanting a newly developed central venous access port (CV-port) that allows catheter insertion into a vein without the use of a peel-away sheath, with a focus on its potential to minimize risks associated with conventional implantation methods.
Materials and methods All procedures were performed using a new device (P-U CelSite Port? MS; Toray Medical, Tokyo, Japan) under ultrasound guidance. The primary endpoint was the implantation success rate. The secondary endpoints were the safety and risk factors for infection in the early postprocedural period ( Results We assessed 523 CV-port implantations performed in a cumulative total of 523 patients (240 men and 283 women; mean age, 61.6?}?13.1 years; range, 18?85 years). All implantations were successfully performed using an inner guide tube and over-the-wire technique through 522 internal jugular veins and one subclavian vein. The mean procedural time was 33.2?}?10.9 min (range 15?112 min). Air embolism, rupture/perforation of the superior vena cava, or hemothorax did not occur during catheter insertion. Eleven (2.1%) intraprocedural complications occurred, including Grade I arrhythmia (n?=?8) and subcutaneous bleeding (n?=?1), Grade II arrhythmia (n?=?1), and Grade IIIa pneumothorax (n?=?1). Furthermore, 496 patients were followed up for???30 days. Six early postprocedural complications were encountered (1.1%), including Grade IIIa infection (n?=?4), catheter occlusion (n?=?1), and skin necrosis due to subcutaneous leakage of trabectedin (n?=?1). These six CV-ports were withdrawn, and no significant risk factors for infection in the early postprocedural period were identified.
Conclusion The implantation of this CV-port device demonstrated comparable success and complication rates to conventional devices, with the added potential benefit of eliminating complications associated with the use of a peel-away sheath. en-copyright= kn-copyright= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawabataTakahiro en-aut-sei=Kawabata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UmakoshiNoriyuki en-aut-sei=Umakoshi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkamotoSoichiro en-aut-sei=Okamoto en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MunetomoKazuaki en-aut-sei=Munetomo en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Central venous catheters kn-keyword=Central venous catheters en-keyword=Vascular access device kn-keyword=Vascular access device en-keyword=Treatment outcome kn-keyword=Treatment outcome en-keyword=Safety kn-keyword=Safety END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=7661 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240916 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurotransmitter recognition by human vesicular monoamine transporter 2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Human vesicular monoamine transporter 2 (VMAT2), a member of the SLC18 family, plays a crucial role in regulating neurotransmitters in the brain by facilitating their uptake and storage within vesicles, preparing them for exocytotic release. Because of its central role in neurotransmitter signalling and neuroprotection, VMAT2 is a target for neurodegenerative diseases and movement disorders, with its inhibitor being used as therapeutics. Despite the importance of VMAT2 in pharmacophysiology, the molecular basis of VMAT2-mediated neurotransmitter transport and its inhibition remains unclear. Here we show the cryo-electron microscopy structure of VMAT2 in the substrate-free state, in complex with the neurotransmitter dopamine, and in complex with the inhibitor tetrabenazine. In addition to these structural determinations, monoamine uptake assays, mutational studies, and pKa value predictions were performed to characterize the dynamic changes in VMAT2 structure. These results provide a structural basis for understanding VMAT2-mediated vesicular transport of neurotransmitters and a platform for modulation of current inhibitor design. en-copyright= kn-copyright= en-aut-name=ImDohyun en-aut-sei=Im en-aut-mei=Dohyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JormakkaMika en-aut-sei=Jormakka en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JugeNarinobu en-aut-sei=Juge en-aut-mei=Narinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KishikawaJun-ichi en-aut-sei=Kishikawa en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTakayuki en-aut-sei=Kato en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugitaYukihiko en-aut-sei=Sugita en-aut-mei=Yukihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NodaTakeshi en-aut-sei=Noda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UemuraTomoko en-aut-sei=Uemura en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShiimuraYuki en-aut-sei=Shiimura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=AsadaHidetsugu en-aut-sei=Asada en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IwataSo en-aut-sei=Iwata en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=3 en-affil=Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University kn-affil= affil-num=4 en-affil=Department of Applied Biology, Kyoto Institute of Technology kn-affil= affil-num=5 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=6 en-affil=Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University kn-affil= affil-num=7 en-affil=Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University kn-affil= affil-num=8 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=9 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=10 en-affil=Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University kn-affil= affil-num=11 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=12 en-affil=Department of Cell Biology, Graduate School of Medicine, Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=5 article-no= start-page=e240601 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=Is subclinical hypothyroidism associated with cardiovascular disease in the elderly? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Subclinical hypothyroidism (SCH) is diagnosed when thyroid function tests show that the serum thyrotropin (TSH) level is elevated and the serum free thyroxine (FT4) level is normal. SCH is mainly caused by Hashimotofs thyroiditis, the prevalence of which increases with aging. Recently, it has been revealed that SCH is associated with risk factors for cardiovascular diseases (CVDs), including atherosclerosis, dyslipidemia and hypertension, leading to cardiovascular morbidity and mortality. However, there are still controversies regarding the diagnosis and treatment of SCH in elderly patients. In this review, we present recent evidence regarding the relationship between SCH and CVD and treatment recommendations for SCH, especially in elderly patients. Studies have shown that SCH is associated with CVD and all-cause mortality. Patients aged less than 65 years showed significant associations of SCH with CVD risk and all-cause mortality, whereas patients aged 65 or older did not show such associations. It was shown that levothyroxine therapy was associated with lower all-cause mortality and cardiovascular mortality in younger SCH patients (<65?70 years) but not in SCH patients aged 65?70 years or older. In elderly SCH patients, levothyroxine treatment should be considered individually according to the patientfs age, serum TSH level, hypothyroid symptoms, CVD risk and other comorbidities. To further elucidate the impact of SCH on CVD in elderly patients, studies should be conducted using age-specific reference ranges of results of thyroid function tests, focusing on elderly patients, specific serum TSH levels, thyroid antibody status and cardiovascular risk factors. en-copyright= kn-copyright= en-aut-name=YamamotoKoichiro en-aut-sei=Yamamoto en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 ORCID= en-aut-name=HasegawaKou en-aut-sei=Hasegawa en-aut-mei=Kou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= 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= en-keyword=cardiovascular disease kn-keyword=cardiovascular disease en-keyword=elderly patients kn-keyword=elderly patients en-keyword=subclinical hypothyroidism kn-keyword=subclinical hypothyroidism en-keyword=thyroid disease kn-keyword=thyroid disease END start-ver=1.4 cd-journal=joma no-vol=487 cd-vols= no-issue= article-no= start-page=137307 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=Co-precipitating calcium phosphate as oral detoxification of cadmium en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bone-eating (also known as osteophagia), found in wild animals, is primarily recognized as a means to supplement phosphorus and calcium intake. Herein, we describe a novel function of bone-eating in detoxifying heavy metal ions through the dissolution and co-precipitation of bone minerals as they travel through the gastrointestinal (GI) tract. In this study, cadmium (Cd), a heavy metal ion, served as a toxic model. We demonstrated that hydroxyapatite (HAp), the major calcium phosphate (CaP) in bone, dissolves in the stomach and acts as a co-precipitant in the intestine for Cd detoxification. We compared HAp to a common antidote, activated charcoal (AC), which did not precipitate within the GI tract. In vitro experiments showed that HAp dissolves under acidic conditions and, upon return to a neutral environment, efficiently re-sequesters Cd. Similarly, oral administration of HAp effectively prevented Cd absorption and accumulation, resulting in enhanced Cd excretion in the feces when compared to AC. A co-precipitating CaP in the GI tract could serve as an excellent detoxification system, as it helps prevent the accumulation of toxic substances and aids in developing appropriate strategies to reduce tissue toxicity. Moreover, understanding this detoxification system would be a valuable indicator for designing efficient detoxification materials. en-copyright= kn-copyright= en-aut-name=BikharudinAhmad en-aut-sei=Bikharudin en-aut-mei=Ahmad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SungPing-chin en-aut-sei=Sung en-aut-mei=Ping-chin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cadmium detoxification kn-keyword=Cadmium detoxification en-keyword=Coprecipitation kn-keyword=Coprecipitation en-keyword=Calcium phosphate kn-keyword=Calcium phosphate en-keyword=Gastrointestinal tract kn-keyword=Gastrointestinal tract END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=2503029 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Polyglycerol]Grafted Graphene Oxide with pH]Responsive Charge]Convertible Surface to Dynamically Control the Nanobiointeractions for Enhanced in Vivo Tumor Internalization en-subtitle= kn-subtitle= en-abstract= kn-abstract=pH-responsive charge-convertible nanomaterials (NMs) ameliorate the treatment of cancer via simultaneously reducing nonspecific interactions during systemic circulation and improving targeted uptake within solid tumors. While promising, little is known about how the pH-responsiveness of charge-convertible NMs directs their interactions with biological systems, leading to compromised performance, including off-target retention and low specificity to tumor cells. In the present study, polyglycerol-grafted graphene oxide bearing amino groups (GOPGNH2) at different densities are reacted with dimethylmaleic anhydride (DMMA), a pH-responsive moiety, to generate a set of charge-convertible GOPGNH-DMMA variants. This permits the assessment of a quantitative correlation between the structure of GOPGNH-DMMA to their pH-responsiveness, their dynamic interactions with proteins and cells, as well as their in vivo biological fate. Through a systematic investigation, it is revealed that GOPGNH115-DMMA prepared from GOPGNH2 with higher amine density experienced fast charge conversion at pH 7.4 to induce non-specific interactions at early stages, whereas GOPGNH60-DMMA and GOPGNH30-DMMA prepared from lower amine density retarded off-target charge conversion to enhance tumor accumulation. Notably, GOPGNH60-DMMA is also associated with enough amounts of proteins under acidic conditions to promote in vivo tumor internalization. The findings will inform the design of pH-responsive NMs for enhanced treatment accuracy and efficacy. en-copyright= kn-copyright= en-aut-name=ZouYajuan en-aut-sei=Zou en-aut-mei=Yajuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=charge conversion kn-keyword=charge conversion en-keyword=in vivo tumor internalization kn-keyword=in vivo tumor internalization en-keyword=non-specific interaction kn-keyword=non-specific interaction en-keyword=pH-responsiveness kn-keyword=pH-responsiveness en-keyword=polyglycerol-grafted graphene oxide kn-keyword=polyglycerol-grafted graphene oxide END start-ver=1.4 cd-journal=joma no-vol=48 cd-vols= no-issue=1 article-no= start-page=51 end-page=59 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=An Underlying Mechanism for the Altered Hypoglycemic Effects of Nateglinide in Rats with Acute Peripheral Inflammation en-subtitle= kn-subtitle= en-abstract= kn-abstract=The hypoglycemic effects of nateglinide (NTG) were examined in rats with acute peripheral inflammation (API) induced by carrageenan treatment, and the mechanisms accounting for altered hypoglycemic effects were investigated. NTG was administered through the femoral vein in control and API rats, and its plasma concentration profile was characterized. The time courses of the changes in plasma glucose and insulin levels were also examined. Although the plasma concentration profile of NTG in API rats was marginally distinguishable from that in control rats, the hypoglycemic effect of NTG was more persistent in API rats than in control rats. In addition, NTG elevated the plasma level of insulin more intensely in API rats than in control rats. Then, the islets of Langerhans were procured by perfusing the pancreas with collagenase solution in control and API rats, and the pancreatic mRNA expression of preproinsulin (Ins1), as well as that of sulfonylurea receptor ABCC8 (Abcc8), were examined. As a result, the expression of preproinsulin and ABCC8 mRNA increased in API rats. These findings suggest that the hypoglycemic effect of NTG was potentiated in API rats due to increased insulin secretion in the pancreas, which was caused by enhanced preproinsulin synthesis and expression of the sulfonylurea receptor. en-copyright= kn-copyright= en-aut-name=TokoHaruka en-aut-sei=Toko en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OginoManami en-aut-sei=Ogino en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiwakiAkane en-aut-sei=Nishiwaki en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KojinaMoeko en-aut-sei=Kojina en-aut-mei=Moeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AibaTetsuya en-aut-sei=Aiba en-aut-mei=Tetsuya 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=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=blood sugar kn-keyword=blood sugar en-keyword=inflammation kn-keyword=inflammation en-keyword=insulin kn-keyword=insulin en-keyword=Langerhans islet kn-keyword=Langerhans islet en-keyword=nateglinide kn-keyword=nateglinide END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=14 article-no= start-page=2406 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250721 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Definitions of, Advances in, and Treatment Strategies for Breast Cancer Oligometastasis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oligometastasis represents a clinically relevant state of limited metastatic disease that could be amenable to selected local therapies in carefully chosen patients. Although initial trials such as SABR-COMET demonstrated a survival benefit with aggressive local treatment, breast cancer was underrepresented. Subsequent breast cancer-specific trials, including NRG-BR002, failed to show a clear survival benefit, highlighting uncertainties and the need for further refinement in patient selection and integration with systemic approaches. The definitions of oligometastasis continue to evolve, incorporating radiological, clinical, and biological features. Advances in imaging and molecular profiling suggest that oligometastatic breast cancer might represent a distinct biological subtype, with potential biomarkers including PIK3CA mutations and YAP/TAZ expression. Organ-specific strategies using stereotactic radiotherapy, surgery, and proton therapy have shown favorable local control in certain settings, though their impact on the overall survival remains under investigation. Emerging techniques, including circulating tumor DNA (ctDNA) analysis, are being explored to improve patient selection and disease monitoring. Ongoing trials may provide further insight into the role of local therapy, particularly in hormone receptor-positive or HER2-positive subtypes. Local and systemic strategies need to be carefully coordinated to optimize the outcomes. This review summarizes the current definitions of and evidence and therapeutic considerations for oligometastatic breast cancer and outlines potential future directions. en-copyright= kn-copyright= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamotoShogo en-aut-sei=Nakamoto en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraYuki en-aut-sei=Fujiwara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KosakaMaya en-aut-sei=Kosaka en-aut-mei=Maya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaraharaYuki en-aut-sei=Narahara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiKento en-aut-sei=Fujii en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaedaReina en-aut-sei=Maeda en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoShutaro en-aut-sei=Kato en-aut-mei=Shutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MimataAsuka en-aut-sei=Mimata en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshiokaRyo en-aut-sei=Yoshioka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuwaharaChihiro en-aut-sei=Kuwahara en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsukiokiTakahiro en-aut-sei=Tsukioki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakahashiYuko en-aut-sei=Takahashi en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwataniTsuguo en-aut-sei=Iwatani en-aut-mei=Tsuguo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TaniokaMaki en-aut-sei=Tanioka en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=oligo-recurrence kn-keyword=oligo-recurrence en-keyword=breast cancer kn-keyword=breast cancer en-keyword=local therapy kn-keyword=local therapy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary tumour resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): a randomised clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Several prospective studies have evaluated the benefit of primary tumour resection (PTR) in de novo Stage IV breast cancer (BC) patients, but it remains controversial. We aimed to investigate whether PTR improves the survival of de novo stage IV BC patients.
Methods: De novo stage IV BC patients were enrolled in the first registration and received systemic therapies according to clinical subtypes. Patients without progression after primary systemic therapy for 3 months were randomly assigned 1:1 to systemic therapy alone (arm A) or PTR plus systemic therapy (arm B). The primary endpoint was overall survival (OS), and the secondary endpoints included local relapse-free survival (LRFS).
Results: Five hundred seventy patients were enrolled between May 5, 2011, and May 31, 2018. Of these, 407 were randomised to arm A (N?=?205) or arm B (N?=?202). The median follow-up time of all randomised patients was 60 months. The difference in OS was not statistically significant (HR 0.86 90% CI 0.69?1.07, one-sided p?=?0.13). Median OS was 69 months (arm A) and 75 months (arm B). In the subgroup analysis, PTR was associated with improved OS in pre-menopausal patients, or those with single-organ metastasis. LRFS in arm B was significantly longer than that in arm A (median LRFS 20 vs. 63 months: HR 0.42, 95% CI 0.33?0.53, p? Conclusions: PTR did not prolong OS. However, it improved local control and might benefit a subset of patients, such as those with premenopausal status or with single-organ metastasis. It also improved local relapse-free survival (LRFS), which is a clinically meaningful outcome in trials of systemic therapy.
Clinical trial registration: UMIN Clinical Trials Registry (UMIN000005586); Japan Registry of Clinical Trials (jRCTs031180151). en-copyright= kn-copyright= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AogiKenjiro en-aut-sei=Aogi en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanagidaYasuhiro en-aut-sei=Yanagida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuneizumiMichiko en-aut-sei=Tsuneizumi en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoNaohito en-aut-sei=Yamamoto en-aut-mei=Naohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoHiroshi en-aut-sei=Matsumoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SutoAkihiko en-aut-sei=Suto en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeKenichi en-aut-sei=Watanabe en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraoMichiko en-aut-sei=Harao en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KanbayashiChizuko en-aut-sei=Kanbayashi en-aut-mei=Chizuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ItohMitsuya en-aut-sei=Itoh en-aut-mei=Mitsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KadoyaTakayuki en-aut-sei=Kadoya en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AnanKeisei en-aut-sei=Anan en-aut-mei=Keisei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaShigeto en-aut-sei=Maeda en-aut-mei=Shigeto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SasakiKeita en-aut-sei=Sasaki en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OgawaGakuto en-aut-sei=Ogawa en-aut-mei=Gakuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SajiShigehira en-aut-sei=Saji en-aut-mei=Shigehira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FukudaHaruhiko en-aut-sei=Fukuda en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IwataHiroji en-aut-sei=Iwata en-aut-mei=Hiroji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Okayama University Hospital kn-affil= affil-num=2 en-affil=Cancer Institute Hospital kn-affil= affil-num=3 en-affil=National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Shizuoka General Hospital kn-affil= affil-num=5 en-affil=Gunma Prefectural Cancer Center kn-affil= affil-num=6 en-affil=Chiba Prefectural Cancer Center kn-affil= affil-num=7 en-affil=Saitama Prefectural Cancer Center kn-affil= affil-num=8 en-affil=National Cancer Center Hospital kn-affil= affil-num=9 en-affil=Hokkaido Cancer Center kn-affil= affil-num=10 en-affil=Jichi Medical University Hospital kn-affil= affil-num=11 en-affil=Niigata Prefectural Cancer Center kn-affil= affil-num=12 en-affil=Hiroshima City Hiroshima Citizenfs Hospital kn-affil= affil-num=13 en-affil=Hiroshima University Hospital kn-affil= affil-num=14 en-affil=Kitakyushu Municipal Medical Center kn-affil= affil-num=15 en-affil=Nagasaki Municipal Medical Center kn-affil= affil-num=16 en-affil=National Cancer Center Hospital kn-affil= affil-num=17 en-affil=National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Fukushima Medical University kn-affil= affil-num=19 en-affil=National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Aichi Cancer Center Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=2 article-no= start-page=53 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Endocrine-Disrupting Chemical, Bisphenol A Diglycidyl Ether (BADGE), Accelerates Neuritogenesis and Outgrowth of Cortical Neurons via the G-Protein-Coupled Estrogen Receptor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bisphenol A diglycidyl ether (BADGE) is the main component of epoxy resin and is used for the inner coating of canned foods and plastic food containers. BADGE can easily migrate from containers and result in food contamination; the compound is known as an endocrine-disrupting chemical. We previously reported that maternal exposure to bisphenol A bis (2,3-dihydroxypropyl) ether (BADGE?2H2O), which is the most detected BADGE derivative not only in canned foods but also in human specimens, during gestation and lactation, could accelerate neuronal differentiation in the cortex of fetuses and induce anxiety-like behavior in juvenile mice. In this study, we investigated the effects of low-dose BADGE?2H2O (1?100 pM) treatment on neurites and the mechanism of neurite outgrowth in cortical neurons. BADGE?2H2O exposure significantly increased the number of dendrites and neurite length in cortical neurons; these accelerating effects were inhibited by estrogen receptor (ER) antagonist ICI 182,780 and G-protein-coupled estrogen receptor (GPER) antagonist G15. BADGE?2H2O down-regulated Hes1 expression, which is a transcriptional repressor, and increased levels of neuritogenic factor neurogenin-3 (Ngn3) in the cortical neurons; the changes were significantly blocked by G15. These data suggest that direct BADGE?2H2O exposure can accelerate neuritogenesis and outgrowth in cortical neurons through down-regulation of Hes1 and by increasing Ngn3 levels through ERs, particularly GPER. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiyamaChiharu en-aut-sei=Nishiyama en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagoshiTakeru en-aut-sei=Nagoshi en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakoAkane en-aut-sei=Miyako en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OnoSuzuka en-aut-sei=Ono en-aut-mei=Suzuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= en-aut-name=TomimotoKana en-aut-sei=Tomimoto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=ZenshoKazumasa en-aut-sei=Zensho en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=7 en-affil=Department of Medical Neurobiology, Okayama University Medical School kn-affil= affil-num=8 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=BADGE kn-keyword=BADGE en-keyword=neurite outgrowth kn-keyword=neurite outgrowth en-keyword=estrogen receptor kn-keyword=estrogen receptor en-keyword=GPER kn-keyword=GPER en-keyword=Hes1 kn-keyword=Hes1 en-keyword=neurogenin-3 kn-keyword=neurogenin-3 END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue=4 article-no= start-page=350 end-page=359 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=N-Phenylphenothiazine Radical Cation with Extended ƒÎ-Systems: Enhanced Heat Resistance of Triarylamine Radical Cations as Near-Infrared Absorbing Dyes en-subtitle= kn-subtitle= en-abstract= kn-abstract=N-Phenylphenothiazine derivatives extended with various aryl groups were designed and synthesized. These derivatives have bent conformation in crystal and exhibit high solubility. Radical cations obtained by one-electron oxidation of these derivatives gave stable radical cations in solution and showed absorption in the near-infrared region. A radical cation was isolated as a stable salt, which exhibited heat resistance up to around 200 ‹C. A design strategy for radical cation-based near-infrared absorbing dyes, which are easily oxidized and stable not only as a solution but in solid form, is described. en-copyright= kn-copyright= en-aut-name=YanoMasafumi en-aut-sei=Yano en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaMinami en-aut-sei=Ueda en-aut-mei=Minami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YajimaTatsuo en-aut-sei=Yajima en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsudoKoichi en-aut-sei=Mitsudo en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KashiwagiYukiyasu en-aut-sei=Kashiwagi en-aut-mei=Yukiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Faculty of Chemistry, Material and Bioengineering, Kansai University kn-affil= affil-num=2 en-affil=Faculty of Chemistry, Material and Bioengineering, Kansai University kn-affil= affil-num=3 en-affil=Faculty of Chemistry, Material and Bioengineering, Kansai University kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Osaka Research Institute of Industrial Science and Technology kn-affil= en-keyword=triarylamines kn-keyword=triarylamines en-keyword=N-phenylphenothiazine kn-keyword=N-phenylphenothiazine en-keyword=radical cation kn-keyword=radical cation en-keyword=near-infrared absorption kn-keyword=near-infrared absorption END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=e003250 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=Clinical impact of combined assessment of myocardial inflammation and fibrosis using myocardial biopsy in patients with dilated cardiomyopathy: a multicentre, retrospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Among patients with dilated cardiomyopathy (DCM), myocardial inflammation and fibrosis are risk factors for poor clinical outcomes. Here, we investigated the combined prognostic value of these two factors, as evaluated using myocardial biopsy samples.
Methods This retrospective and multicentre study included patients with DCM?defined as LVEF of ?45% and left diastolic diameter of >112% of predicted value, without evidence of secondary or ischaemic cardiomyopathy. In myocardial biopsy samples, inflammatory cells were counted using immunohistochemistry, and Massonfs Trichrome staining was performed to quantify the myocardial fibrosis as collagen area fraction (CAF). Higher myocardial inflammation was defined as leucocytes of ?14/mm?, including ?4 monocytes/mm?, with CD3+ T lymphocytes of?7/mm?. Greater myocardial fibrosis was defined as CAF of>5.9% by the Youdenfs index. The primary endpoint was cardiac death or left ventricular assist device implantation.
Results A total of 255 DCM patients were enrolled (average age, 53.1 years; 78% males). Within this cohort, the mean LVEF was 28.0%, mean CAF was 10.7% and median CD3+ cell count was 8.3/mm2. During the median follow-up period of 2688 days, 46 patients met the primary endpoint. Multivariable Cox proportional hazard analyses revealed that CD3+ cell count and CAF were independent determinants of the primary endpoint. Kaplan?Meier analysis showed that patients with both higher myocardial inflammation and greater fibrosis had the worst prognosis (log-rank p<0.001). When myocardial inflammation was graded as one of three degrees: T lymphocytes of <13/mm? (low); 13 of 13.1?23.9/mm? (moderate); and T lymphocytes of ?24?/mm? (high), patients with moderate inflammation exhibited a superior survival rate when CAF was ?5.9%, but a worse survival rate when CAF was >5.9%.
Conclusions Having both biopsy-proven higher myocardial inflammation and greater fibrosis predicted the worst clinical prognosis in patients with DCM. en-copyright= kn-copyright= en-aut-name=NakayamaTakafumi en-aut-sei=Nakayama en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgoKeiko Ohta en-aut-sei=Ogo en-aut-mei=Keiko Ohta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuganoYasuo en-aut-sei=Sugano en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokokawaTetsuro en-aut-sei=Yokokawa en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanamoriHiromitsu en-aut-sei=Kanamori en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkedaYoshihiko en-aut-sei=Ikeda en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiroeMichiaki en-aut-sei=Hiroe en-aut-mei=Michiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HatakeyamaKinta en-aut-sei=Hatakeyama en-aut-mei=Kinta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Ishibashi-UedaHatsue en-aut-sei=Ishibashi-Ueda en-aut-mei=Hatsue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DohiKaoru en-aut-sei=Dohi en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AnzaiToshihisa en-aut-sei=Anzai en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SeoYoshihiro en-aut-sei=Seo en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Imanaka-YoshidaKyoko en-aut-sei=Imanaka-Yoshida en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Cardiology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=3 en-affil=Department of Cardiology, Keiyu Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Fukushima Medical University kn-affil= affil-num=5 en-affil=Department of Cardiology, Gifu University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=7 en-affil=Department of Cardiology, National Center for Global Health and Medicine kn-affil= affil-num=8 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=9 en-affil=Department of Pathology, National Cerebral and Cardiovascular Center kn-affil= affil-num=10 en-affil=Center for Advanced Heart Failure, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Cardiology and Nephrology, Mie University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Cardiology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=14 en-affil=Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=2 article-no= start-page=606 end-page=617 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanistic Insights Into Oxidative Response of Heat Shock Factor 1 Condensates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heat shock factor 1 (Hsf1), a hub protein in the stress response and cell fate decisions, senses the strength, type, and duration of stress to balance cell survival and death through an unknown mechanism. Recently, changes in the physical property of Hsf1 condensates due to persistent stress have been suggested to trigger apoptosis, highlighting the importance of biological phase separation and transition in cell fate decisions. In this study, the mechanism underlying Hsf1 droplet formation and oxidative response was investigated through 3D refractive index imaging of the internal architecture, corroborated by molecular dynamics simulations and biophysical/biochemical experiments. We found that, in response to oxidative conditions, Hsf1 formed liquid condensates that suppressed its internal mobility. Furthermore, these conditions triggered the hyper-oligomerization of Hsf1, mediated by disulfide bonds and secondary structure stabilization, leading to the formation of dense core particles in the Hsf1 droplet. Collectively, these data demonstrate how the physical property of Hsf1 condensates undergoes an oxidative transition by sensing redox conditions to potentially drive cell fate decisions. en-copyright= kn-copyright= en-aut-name=KawagoeSoichiro en-aut-sei=Kawagoe en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsusakiMotonori en-aut-sei=Matsusaki en-aut-mei=Motonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MabuchiTakuya en-aut-sei=Mabuchi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgasawaraYuto en-aut-sei=Ogasawara en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=IshimoriKoichiro en-aut-sei=Ishimori en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaioTomohide en-aut-sei=Saio en-aut-mei=Tomohide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=2 en-affil=Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=3 en-affil=Frontier Research Institute for Interdisciplinary Sciences, Tohoku University kn-affil= affil-num=4 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Chemistry, Faculty of Science, Hokkaido University kn-affil= affil-num=7 en-affil=Institute of Advanced Medical Sciences, Tokushima University kn-affil= en-keyword=heat shock factor 1 kn-keyword=heat shock factor 1 en-keyword=oxidative hyper-oligomerization kn-keyword=oxidative hyper-oligomerization en-keyword=biological phase transition kn-keyword=biological phase transition en-keyword=stress response kn-keyword=stress response en-keyword=biophysics kn-keyword=biophysics END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=15 article-no= start-page=2290 end-page=2294 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and Genetic Analyses of SPG7 in Japanese Patients with Undiagnosed Ataxia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Spastic paraplegia 7 (SPG7) is an autosomal recessive neurodegenerative disorder caused by biallelic pathogenic variants in SPG7. It is predominantly characterized by adult-onset slowly progressive spastic paraparesis. While SPG7 presenting with ataxia with or without spasticity is relatively common in Europe and North America, it is considered rare in Japan. This study aimed to identify SPG7 patients among those with undiagnosed ataxia within the Japanese population.
Methods We retrospectively selected 351 patients with undiagnosed ataxia, excluding those with secondary and common spinocerebellar ataxia. Whole-exome sequence analysis was conducted, and homozygosity of the identified variants was confirmed using droplet digital polymerase chain reaction (ddPCR).
Results Among the 351 patients, 2 were diagnosed with SPG7, and homozygosity was confirmed by ddPCR. Both patients carried homozygous pathogenic variants in SPG7: c.1948G>A, p.Asp650Asn, and c.1192C>T, p.Arg398Ter (NM_003119.4). Clinically, both patients presented with progressive ataxia. In addition, Patient 1 exhibited partial ophthalmoplegia and spastic paraparesis, whereas Patient 2 demonstrated cerebellar ataxia without spasticity.
Conclusion The rarity of SPG7 in Japan may be attributed to variation in the minor allele frequency of the c.1529C>T, p.Ala510Val variant, which is more prevalent in Europe and North America than in other areas. en-copyright= kn-copyright= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HinoRimi en-aut-sei=Hino en-aut-mei=Rimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujinoGo en-aut-sei=Fujino en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaiYuto en-aut-sei=Sakai en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=K. IwataNobue en-aut-sei=K. Iwata en-aut-mei=Nobue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, International University of Health and Welfare Mita Hospital kn-affil= affil-num=6 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, International University of Health and Welfare Mita Hospital kn-affil= affil-num=9 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=cerebellar ataxia kn-keyword=cerebellar ataxia en-keyword=spastic paraparesis kn-keyword=spastic paraparesis en-keyword=whole-exome sequence analysis kn-keyword=whole-exome sequence analysis en-keyword=SPG7 kn-keyword=SPG7 END start-ver=1.4 cd-journal=joma no-vol=156 cd-vols= no-issue=2 article-no= start-page=151 end-page=159.e1 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=The greater palatine nerve and artery both supply the maxillary teeth en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background. It is generally accepted that the greater palatine nerve and artery supply the palatal mucosa, gingiva, and glands, but not the bone or tooth adjacent to those tissues. When the bony palate is observed closely, multiple small foramina are seen on the palatal surface of the alveolar process. The authors hypothesized that the greater palatine nerve and artery might supply the maxillary teeth via the foramina on the palatal surface of the alveolar process and the superior alveolar nerve and artery. The authors aimed to investigate the palatal innervation and blood supply of the maxillary teeth.
Methods. Eight cadaveric maxillae containing most teeth or alveolar sockets were selected. The mean age at the time of death was 82.4 years. The samples were examined with colored water injection, latex injection, microcomputed tomography with contrast dye, gross anatomic dissection, and histologic observation.
Results. Through both injection studies and microcomputed tomographic analysis, the authors found that the small foramina on and around the greater palatine groove connected to the alveolar process and tooth sockets. The small foramina in the greater palatine and incisive canal also continued inside the alveolar process and the tooth sockets.
Conclusions. The alveolar branches of the greater palatine nerve and artery as well as the nasopalatine nerve and sphenopalatine artery supply maxillary teeth, alveolar bone, and periodontal tissue via the palatal alveolar foramina with superior alveolar nerves and arteries.
Practical Implications. This knowledge is essential for dentists when administering local anesthetic to the maxillary teeth and performing an osteotomy. Anatomic and dental textbooks should be updated with this new knowledge for better patient care. en-copyright= kn-copyright= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=AnbalaganMuralidharan en-aut-sei=Anbalagan en-aut-mei=Muralidharan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZouBinghao en-aut-sei=Zou en-aut-mei=Binghao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToriumiTaku en-aut-sei=Toriumi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TubbsR. Shane en-aut-sei=Tubbs en-aut-mei=R. Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Gross and Clinical Anatomy, Department of Anatomy, School of Medicine, Kurume University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Structural and Cellular Biology, School of Medicine, Tulane University kn-affil= affil-num=4 en-affil=Department of Structural and Cellular Biology, School of Medicine, Tulane University kn-affil= affil-num=5 en-affil=Department of Anatomy, School of Life Dentistry at Niigata, The Nippon Dental University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=University of Queensland kn-affil= en-keyword=Maxillary teeth kn-keyword=Maxillary teeth en-keyword=dental pulp kn-keyword=dental pulp en-keyword=anatomy kn-keyword=anatomy en-keyword=nerve block kn-keyword=nerve block en-keyword=root canal treatment kn-keyword=root canal treatment en-keyword=cadaver kn-keyword=cadaver END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=10 article-no= start-page=1151 end-page=1159 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=NCF-1 plays a pivotal role in the survival of adenocarcinoma cells of pancreatic and gastric origins en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reactive oxygen species (ROS) play a pivotal biological role in cells, with ROS function differing depending on cellular conditions and the extracellular environment. Notably, ROS act as cytotoxic factors to eliminate infectious pathogens or promote cell death under cellular stress, while also facilitating cell growth (via ROS-sensing pathways) by modifying gene expression. Among ROS-related genes, neutrophil cytosolic factor-1 (NCF-1; p47phox) was identified as a ROS generator in neutrophils. This product is a subunit of a cytosolic NADPH oxidase complex activated in response to pathogens such as bacteria and viruses. NCF-1 has been examined primarily in terms of ROS-production pathways in macrophages and neutrophils; however, the expression of this protein and its biological role in cancer cells remain unclear. Here, we report expression of NCF-1 in pancreatic and gastric cancers, and demonstrate its biological significance in these tumor cells. Abundant expression of NCF-1 was observed in pancreatic adenocarcinoma (PDAC) lines and in patient tissues, as well as in gastric adenocarcinomas. Accumulation of the protein was also detected in the invasive/metastatic foci of these tumors. Unexpectedly, BxPC-3 underwent apoptotic cell death when transfected with a small interfering RNA (siRNA) specific to NCF-1, whereas the cells treated with a control siRNA proliferated in a time-dependent manner. A similar phenomenon was observed in HSC-58, a poorly differentiated gastric adenocarcinoma line. Consequently, the tumor cells highly expressing NCF-1 obtained coincident accumulation of ROS and reduced glutathione (GSH) with expression of glutathione peroxidase 4 (GPX4), a quencher involved in ferroptosis. Unlike the conventional role of ROS as a representative cytotoxic factor, these findings suggest that NCF-1-mediated ROS generation may be required for expansive growth of PDAC and gastric cancers. en-copyright= kn-copyright= en-aut-name=Furuya-IkudeChiemi en-aut-sei=Furuya-Ikude en-aut-mei=Chiemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KittaAkane en-aut-sei=Kitta en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomonobuNaoko en-aut-sei=Tomonobu en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawasakiYoshihiro en-aut-sei=Kawasaki en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=2 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=5 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= en-keyword=NCF-1 (p47phox) kn-keyword=NCF-1 (p47phox) en-keyword=ROS kn-keyword=ROS en-keyword=Cancer kn-keyword=Cancer en-keyword=Tumor growth kn-keyword=Tumor growth en-keyword=Apoptosis kn-keyword=Apoptosis END start-ver=1.4 cd-journal=joma no-vol=472 cd-vols= no-issue= article-no= start-page=123486 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical, neuroimaging and genetic findings in the Japanese case series of CLCN2-related leukoencephalopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Biallelic loss-of-function variants in CLCN2 lead to CLCN2-related leukoencephalopathy (CC2L), also called leukoencephalopathy with ataxia (LKPAT). CC2L is characterized clinically by a spectrum of clinical presentations including childhood- to adult-onset mild ataxia, spasticity, cognitive decline, and vision loss as well as typical MRI findings of symmetrical high signal intensities on the DWIs/T2WIs of the middle cerebellar peduncles (MCPs). We searched for pathogenic variants of CLCN2 in a case series of undiagnosed leukoencephalopathy accompanied by MCP signs, which led to the identification of four Japanese patients with CC2L. All the patients carried at least one allele of c.61dupC (p.Leu21Profs*27) in CLCN2, including compound heterozygosity with either the novel pathogenic variant c.983 + 2 T > A or the previously reported pathogenic variant c.1828C > T (p.Arg610*). Of note, all the four previously reported cases from Japan also harbored c.61dupC, and no reports of this variant have been documented from outside Japan. The allele frequency of c.61dupC in the Japanese population is 0.002152, raising the possibility of a relatively high prevalence of CC2L in Japan. Patients in this study developed symptoms after the age of 30, and demonstrated neurological signs including cerebellar ataxia, pyramidal signs, and mild cognitive impairment, consistent with previous reports. One male patient had two children, supporting preserved fertility, and another patient had calcifications in the cerebral and cerebellar surfaces. These findings provide valuable insights into the broader clinical and genetic spectra of CC2L in the Japanese population, and emphasize the importance of considering this disease in the differential diagnoses of leukoencephalopathy with MCP signs. en-copyright= kn-copyright= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChoTakusei en-aut-sei=Cho en-aut-mei=Takusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaruseHiroya en-aut-sei=Naruse en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakiyamaYoshio en-aut-sei=Sakiyama en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SumiKensho en-aut-sei=Sumi en-aut-mei=Kensho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchioNaohiro en-aut-sei=Uchio en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatakeAkane en-aut-sei=Satake en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakiyamaYoshihisa en-aut-sei=Takiyama en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsushitaTakuya en-aut-sei=Matsushita en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OmaeYosuke en-aut-sei=Omae en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KawaiYosuke en-aut-sei=Kawai en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TokunagaKatsushi en-aut-sei=Tokunaga en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Division of Neurology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University kn-affil= affil-num=7 en-affil=Department of Neurology, Mitsui Memorial Hospital kn-affil= affil-num=8 en-affil=Department of Neurology, Mitsui Memorial Hospital kn-affil= affil-num=9 en-affil=Department of Neurology, Fuefuki Central Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Fuefuki Central Hospital kn-affil= affil-num=11 en-affil=Department of Neurology, Kochi Medical School, Kochi University kn-affil= affil-num=12 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=13 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=14 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=15 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=16 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=17 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=Leukodystrophy kn-keyword=Leukodystrophy en-keyword=CC2L kn-keyword=CC2L en-keyword=CLCN2 kn-keyword=CLCN2 en-keyword=MCP sign kn-keyword=MCP sign END start-ver=1.4 cd-journal=joma no-vol=219 cd-vols= no-issue= article-no= start-page=104944 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Establishment of a transgenic strain for the whole brain calcium imaging in larval medaka fish (Oryzias latipes) en-subtitle= kn-subtitle= en-abstract= kn-abstract=GCaMP-based calcium imaging is a powerful tool for investigating neural function in specific neurons. We generated transgenic (Tg) medaka strains expressing jGCaMP7s across extensive brain regions under the control of the gap43 promoter. Using these Tg larvae, calcium imaging successfully detected a tricaine-induced suppression of spontaneous neural activity and topographical visual responses in the optic tectum elicited by moving paramecia or optical fiber stimulation. These results indicate that our Tg medaka strains provide a versatile platform for investigating neural dynamics and their responses to various stimuli. en-copyright= kn-copyright= en-aut-name=SekiTakahide en-aut-sei=Seki en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyanariKazuhiro en-aut-sei=Miyanari en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiraishiAsuka en-aut-sei=Shiraishi en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsudaSachiko en-aut-sei=Tsuda en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=2 en-affil=Graduate School of Science and Engineering, Saitama University kn-affil= affil-num=3 en-affil=Graduate School of Science and Engineering, Saitama University kn-affil= affil-num=4 en-affil=Graduate School of Science and Engineering, Saitama University kn-affil= affil-num=5 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= en-keyword=gap43 kn-keyword=gap43 en-keyword=JGCaMP7s kn-keyword=JGCaMP7s en-keyword=Ac/Ds kn-keyword=Ac/Ds en-keyword=Visuotopy kn-keyword=Visuotopy en-keyword=slc2a15b kn-keyword=slc2a15b END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=12 article-no= start-page=2664 end-page=2671 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241014 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long]term outcomes of endoscopic resection of superficial esophageal squamous cell carcinoma in late]elderly patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: As the population ages, the number of elderly patients with superficial esophageal squamous cell carcinoma (ESCC) is increasing. We aimed to clarify the indications for endoscopic resection (ER) in late-elderly patients with ESCC in terms of life expectancy.
Methods: Patients aged ?75 years who underwent ER for ESCC at our institution from January 2005 to December 2018 were enrolled. Clinical data, including the Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists physical status (ASA-PS), Charlson comorbidity index, and prognostic nutritional index (PNI), were collected at the time of ER. The main outcome measure was overall survival (OS).
Results: Two hundred eight consecutive patients were enrolled. The patients' median age was 78 years (range, 75?89 years). The 5-year follow-up rate was 88.5% (median follow-up period, 6.6 years). The 5-year OS rate was 79.2% (95% confidence interval [CI], 72.2?84.8), and 5-year net survival standardized for age, sex, and calendar year was 1.04 (95% CI, 0.98?1.09). In the multivariate analysis, an ASA-PS of 3 (hazard ratio, 2.45; 95% CI, 1.16?5.17) and PNI of <44.0 (hazard ratio, 2.73; 95% CI, 1.38?5.40) were independent prognostic factors. When neither of these factors was met, the 5-year OS rate was 87.8% (95% CI, 80.0?92.9), and 5-year net survival was 1.08 (95% CI, 1.02?1.14).
Conclusions: ER for ESCC in late-elderly patients may improve life expectancy. ER is recommended in patients with a good ASA-PS and PNI. en-copyright= kn-copyright= en-aut-name=MatsuedaKatsunori en-aut-sei=Matsueda en-aut-mei=Katsunori 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=FukuiKeisuke en-aut-sei=Fukui en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirataShoichiro en-aut-sei=Hirata en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=InooShoko en-aut-sei=Inoo en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=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=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro 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 Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Faculty of Societal Safety Sciences, Kansai University 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 Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=endoscopic resection kn-keyword=endoscopic resection en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=late-elderly patient kn-keyword=late-elderly patient en-keyword=long-term outcome kn-keyword=long-term outcome END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=12 article-no= start-page=1697 end-page=1702 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240615 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gastric Mucosa-associated Lymphoid Tissue Lymphoma That Relapsed after 11 Years Subsequent to Achieving Complete Remission en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 38-year-old Japanese man was diagnosed with extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue in the stomach (gastric MALT lymphoma). Fluorescence in situ hybridization analysis revealed the absence of t (11;18) (q21;q21) translocation but the presence of extra copies of MALT1, indicating tetrasomy 18. Helicobacter pylori eradication led to complete remission (CR). However, the gastric MALT lymphoma relapsed after 11 years old. This case underscores the need for long-term observation (>10 years) of patients with gastric MALT lymphoma. Further investigation is warranted to elucidate the correlation between trisomy/tetrasomy 18 and the recurrence propensity. en-copyright= kn-copyright= en-aut-name=InooShoko en-aut-sei=Inoo en-aut-mei=Shoko 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=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OotukaMotoyuki en-aut-sei=Ootuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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 Hospital kn-affil= affil-num=4 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=gastric MALT lymphoma kn-keyword=gastric MALT lymphoma en-keyword=H. pylori kn-keyword=H. pylori en-keyword=relapse kn-keyword=relapse 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= dt-pub= dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title= en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=e261 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alcohol consumption, multiple Lugol]voiding lesions, and field cancerization en-subtitle= kn-subtitle= en-abstract= kn-abstract=The development of multiple squamous cell carcinomas (SCC) in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, and esophagus, is explained by field cancerization and is associated with alcohol consumption and cigarette smoking. We reviewed the association between alcohol consumption, multiple Lugol-voiding lesions, and field cancerization, mainly based on the Japan Esophageal Cohort study. The Japan Esophageal Cohort study is a prospective cohort study that enrolled patients with esophageal SCC after endoscopic resection. Enrolled patients received surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months. The Japan Esophageal Cohort study showed that esophageal SCC and head and neck SCC that developed after endoscopic resection for esophageal SCC were associated with genetic polymorphisms related to alcohol metabolism. They were also associated with Lugol-voiding lesions grade in the background esophageal mucosa, the score of the health risk appraisal model for predicting the risk of esophageal SCC, macrocytosis, and score on alcohol use disorders identification test. The standardized incidence ratio of head and neck SCC in patients with esophageal SCC after endoscopic resection was extremely high compared to the general population. Drinking and smoking cessation is strongly recommended to reduce the risk of metachronous esophageal SCC after treatment of esophageal SCC. Risk factors for field cancerization provide opportunities for early diagnosis and minimally invasive treatment. Lifestyle guidance of alcohol consumption and cigarette smoking for esophageal precancerous conditions, which are endoscopically visualized as multiple Lugol-voiding lesions, may play a pivotal role in decreasing the incidence and mortality of esophageal SCC. en-copyright= kn-copyright= en-aut-name=KatadaChikatoshi en-aut-sei=Katada en-aut-mei=Chikatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoyamaTetsuji en-aut-sei=Yokoyama en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanoTomonori en-aut-sei=Yano en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHaruhisa en-aut-sei=Suzuki en-aut-mei=Haruhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FurueYasuaki en-aut-sei=Furue en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoKeiko en-aut-sei=Yamamoto en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoyamaHisashi en-aut-sei=Doyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoikeTomoyuki en-aut-sei=Koike en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamaokiMasashi en-aut-sei=Tamaoki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawataNoboru en-aut-sei=Kawata en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraoMotohiro en-aut-sei=Hirao en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=OgataTakashi en-aut-sei=Ogata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatagiriAtsushi en-aut-sei=Katagiri en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamanouchiTakenori en-aut-sei=Yamanouchi en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KiyokawaHirofumi en-aut-sei=Kiyokawa en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawakuboHirofumi en-aut-sei=Kawakubo en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KonnoMaki en-aut-sei=Konno en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhashiShinya en-aut-sei=Ohashi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KondoYuki en-aut-sei=Kondo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KishimotoYo en-aut-sei=Kishimoto en-aut-mei=Yo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KanoKoichi en-aut-sei=Kano en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MureKanae en-aut-sei=Mure en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HayashiRyuichi en-aut-sei=Hayashi en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IshikawaHideki en-aut-sei=Ishikawa en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MutoManabu en-aut-sei=Muto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Health and Promotion, National Institute of Public Health kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Endoscopy Division, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=6 en-affil=Division of Endoscopy, Hokkaido University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Ishikawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=10 en-affil=Division of Endoscopy, Shizuoka Cancer Center kn-affil= affil-num=11 en-affil=Department of Surgery, National Hospital Organization Osaka National Hospital kn-affil= affil-num=12 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= affil-num=14 en-affil=Department of Medicine, Division of Gastroenterology, Showa University Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Kumamoto Regional Medical Center kn-affil= affil-num=16 en-affil=Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= affil-num=17 en-affil=Department of Surgery, Kawasaki Municipal Kawasaki Hospital kn-affil= affil-num=18 en-affil=Department of Gastroenterology, Tochigi Cancer Center kn-affil= affil-num=19 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=20 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=21 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=22 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital kn-affil= affil-num=23 en-affil=Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine kn-affil= affil-num=24 en-affil=Department of Public Health, Wakayama Medical University School of Medicine kn-affil= affil-num=25 en-affil=Department of Head and Neck Surgery, National Cancer Center Hospital East kn-affil= affil-num=26 en-affil=Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine kn-affil= affil-num=27 en-affil=Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center kn-affil= affil-num=28 en-affil=Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=alcohol kn-keyword=alcohol en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=field cancerization kn-keyword=field cancerization en-keyword=head and neck cancer kn-keyword=head and neck cancer en-keyword=JEC study kn-keyword=JEC study END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=8 article-no= start-page=e18026 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Commissioning of respiratory]gated 4D dynamic dose calculations for various gating widths without spot timestamp in proton pencil beam scanning en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Proton pencil beam scanning (PBS) is susceptible to dose degradation because of interplay effects on moving targets. For cases of unacceptable motion, respiratory-gated (RG) irradiation is an effective alternative to free breathing (FB) irradiation. However, the introduction of RG irradiation with larger gate widths (GW) is hindered by interplay effects, which are analogous to those observed with FB irradiation. Accurate estimation of interplay effects can be performed by recording spot timestamps. However, our machine lacks this feature, making it imperative to find an alternative approach. Thus, we developed an RG 4-dimensional dynamic dose (RG-4DDD) system without spot timestamps.
Purpose: This study aimed to investigate the accuracy of calculated doses from the RG-4DDD system for PBS plans with varying breathing curves, amplitudes, and periods for 10%?50% GW.
Methods: RG-4DDDs were reconstructed using in-house developed software that assigned timestamps to individual spots, integrated start times for spills with breathing curves, and utilized deformable registrations for dose accumulation. Three cubic verification plans were created using a heterogeneous phantom. Additionally, typical liver and lung cases were employed for patient plan validation. Single- and multi-field-optimized (SFO and IMPT) plans (ten beams in total) were created for the liver and lung cases in a homogeneous phantom. Lateral profile measurements were obtained under both motion and no-motion conditions using a 2D ionization chamber array (2D-array) and EBT3 Gafchromic films on the CIRS dynamic platform. Breathing curves from the cubic plans were used to assess nine patterns of sine curves, with amplitudes of 5.0?10.0 mm (10.0?20.0 mm target motions) and periods of 3?6 sec. Patient field verifications were conducted using a representative patient curve with an average amplitude of 6.4 mm and period of 3.2 sec. Additional simulations were performed assuming a } 10% change in assigned timestamps for the dose rate (DR), spot spill (0.08-s), and gate time delay (0.1-s) to evaluate the effect of parameter selection on our 4DDD models. The 4DDDs were compared with measured values using the 2D gamma index and absolute doses over that required for dosing 95% of the target.
Results: The 2D-array measurements showed that average gamma scores for the reference (no motion) and 4DDD plans for all GWs were at least 99.9 } 0.2% and 98.2 } 2.4% at 3%/3 mm, respectively. The gamma scores of the 4DDDs in film measurements exceeded 95.4% and 92.9% at 2%/2 mm for the cubic and patient plans, respectively. The 4DDD calculations were acceptable under DR changes of }10% and both spill and gate time delays of }0.18 sec. For the 4DDD plan using all GWs for all measurement points, the absolute point differences for all validation plans were within }5.0% for 99.1% of the points.
Conclusions: The RG-4DDD calculations (less than 50% GW) of the heterogeneous and actual patient plans showed good agreement with measurements for various breathing curves in the amplitudes and periods described above. The proposed system allows us to evaluate actual RG irradiation without requiring the ability to record spot timestamps. en-copyright= kn-copyright= en-aut-name=TominagaYuki en-aut-sei=Tominaga en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WakisakaYushi en-aut-sei=Wakisaka en-aut-mei=Yushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoTakahiro en-aut-sei=Kato en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchiharaMasaya en-aut-sei=Ichihara en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YasuiKeisuke en-aut-sei=Yasui en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SasakiMotoharu en-aut-sei=Sasaki en-aut-mei=Motoharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=NishioTeiji en-aut-sei=Nishio en-aut-mei=Teiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic kn-affil= affil-num=2 en-affil=Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic kn-affil= affil-num=3 en-affil=Department of Radiological Sciences, School of Health Sciences, Fukushima Medical University kn-affil= affil-num=4 en-affil=Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka kn-affil= affil-num=5 en-affil=School of Medical Sciences, Fujita Health University kn-affil= affil-num=6 en-affil=Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=7 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka kn-affil= en-keyword=4D dynamic dose kn-keyword=4D dynamic dose en-keyword=interplay effect kn-keyword=interplay effect en-keyword=pencil beam scanning kn-keyword=pencil beam scanning en-keyword=proton therapy kn-keyword=proton therapy en-keyword=respiratory gating kn-keyword=respiratory gating END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=8 article-no= start-page=afaf224 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oestrogen replacement combined with resistance exercise in older women with knee osteoarthritis: a randomised, double-blind, placebo-controlled clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Interventions targeting physical function decline in older women with knee osteoarthritis (KOA) are vital for healthy ageing. The additive benefits of combining oestrogen replacement therapy (ERT) with resistance exercise remain unclear.
Objective: To evaluate the additive effect of low-dose ERT on physical performance when combined with a muscle resistance exercise programme (MREP) in older women with KOA.
Design: This is a placebo-controlled, double-blind, randomised clinical trial.
Subjects: The subjects were community-dwelling women aged ?65 years with chronic knee pain and KOA diagnosis.
Methods: Participants completed a 3-month MREP and were randomised to receive daily low-dose transdermal ERT (oestradiol 0.54 mg/day) or placebo. Outcomes were assessed at baseline, postintervention and 12 months later. The primary outcome was change in 30-second chair stand test (CS-30) score. Secondary outcomes included muscle mass, knee extension strength, walking performance, metabolic indicators, knee pain scale and 12-item short-form health survey (SF-12). Between-group differences in CS-30 changes were analysed using a linear regression model based on the intention-to-treat principle.
Results: Among 168 individuals screened, 75 participants (mean age 73.8 years, SD 5.8) were enrolled and randomised into an ERT group (n?=?37) or a placebo group (n?=?38). Baseline CS-30 scores were 14.81 (SD 3.95) in the ERT group and 15.58 (SD 3.48) in the placebo group. At 3 months, mean changes were 2.59 (SD 2.58) and 1.79 (SD 2.28) repetitions, respectively. The primary analysis showed no statistically significant between-group difference [regression coefficient: 0.81 (95% CI: ?0.31, 1.92); P?=?.16]. Post hoc subgroup and sensitivity analyses suggested that benefits may exist among early-stage KOA participants. SF-12 mental health scores also improved significantly in the ERT group. No serious adverse events occurred.
Conclusions: ERT did not confer significant additive benefits to resistance exercise overall but may improve outcomes in early-stage KOA and mental health domains. These exploratory findings warrant further investigation. en-copyright= kn-copyright= en-aut-name=MitomaTomohiro en-aut-sei=Mitoma en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OobaHikaru en-aut-sei=Ooba en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiKasumi en-aut-sei=Takahashi en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTsunemasa en-aut-sei=Kondo en-aut-mei=Tsunemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaTomohiro en-aut-sei=Ikeda en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=2 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=3 en-affil=Obstetrics and Gynecology, Ochiai Hospital kn-affil= affil-num=4 en-affil=Obstetrics and Gynecology, Ochiai Hospital kn-affil= affil-num=5 en-affil=Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=7 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= affil-num=8 en-affil=Medical Development Field, Center for Innovative Clinical Medicine, Okayama University kn-affil= en-keyword=oestrogen replacement therapy kn-keyword=oestrogen replacement therapy en-keyword=muscle resistance exercise kn-keyword=muscle resistance exercise en-keyword=knee osteoarthritis kn-keyword=knee osteoarthritis en-keyword=physical performance kn-keyword=physical performance en-keyword=randomised controlled trial kn-keyword=randomised controlled trial en-keyword=older people kn-keyword=older people END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=2 article-no= start-page=ivae021 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plasma concentrations of histidine-rich glycoprotein in primary graft dysfunction after lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=OBJECTIVES: Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction.
METHODS: According to the primary graft dysfunction grade at post-transplant 72?h, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0?1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7?days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation.
RESULTS: A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72?h was significantly lower in the severe primary graft dysfunction group (n?=?7) than in the other two groups [non-primary graft dysfunction group (n?=?43), P?=?0.042; moderate primary graft dysfunction group (n?=?18), P?=?0.040]. Patients with plasma histidine-rich glycoprotein concentration ?34.4??g/ml at post-transplant 72?h had significantly better chronic lung allograft dysfunction-free survival (P?=?0.012) and overall survival (P?=?0.037) than those with the concentration <34.4??g/ml.
CONCLUSIONS: Plasma histidine-rich glycoprotein concentrations at post-transplant 72?h might be associated with the risk of development of primary graft dysfunction. en-copyright= kn-copyright= en-aut-name=ShiotaniToshio en-aut-sei=Shiotani en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 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=6 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=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=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=5 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital kn-affil= en-keyword=Lung transplantation kn-keyword=Lung transplantation en-keyword=Primary graft dysfunction kn-keyword=Primary graft dysfunction en-keyword=Histidine-rich glycoprotein kn-keyword=Histidine-rich glycoprotein en-keyword=Chronic lung allograft dysfunction kn-keyword=Chronic lung allograft dysfunction en-keyword=Overall survival kn-keyword=Overall survival END start-ver=1.4 cd-journal=joma no-vol=207 cd-vols= no-issue= article-no= start-page=108683 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Intracranial activity of sotorasib vs docetaxel in pretreated KRAS G12C-mutated advanced non-small cell lung cancer from a global, phase 3, randomized controlled trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To assess the efficacy and safety of sotorasib in patients with brain metastases using data from the phase 3 CodeBreaK 200 study, which evaluated sotorasib in adults with pretreated advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC).
Materials and methods: Patients with KRAS G12C-mutated NSCLC who progressed after platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1:1 to sotorasib or docetaxel. An exploratory post-hoc analysis evaluated central nervous system (CNS) progression-free survival (PFS) and time to CNS progression in patients with treated and stable brain metastases at baseline. Measures were assessed by blinded independent central review per study-modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.
Results: Of the patients randomly assigned to receive sotorasib (n=171) or docetaxel (n=174), baseline CNS metastases were present in 40 (23%) and 29 (17%) patients, respectively. With a median follow-up of 20.0 months for this patient subgroup, median CNS PFS was longer with sotorasib compared with docetaxel (9.6 vs 4.5 months; hazard ratio, 0.43 [95% CI, 0.20?0.92]; P=0.02). Among patients with baseline treated CNS lesions of ?10 mm, the percentage of patients who achieved CNS tumor shrinkage of ?30% was two-fold higher with sotorasib than docetaxel (33.3% vs 15.4%). Treatment-related adverse events among patients with CNS lesions at baseline were consistent with those of the overall study population.
Conclusions: These results suggest intracranial activity with sotorasib complements the overall PFS benefit observed with sotorasib vs docetaxel, with safety outcomes similar to those in the general CodeBreaK 200 population.
Clinical trials registration number: NCT04303780. en-copyright= kn-copyright= en-aut-name=DingemansAnne-Marie C. en-aut-sei=Dingemans en-aut-mei=Anne-Marie C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SyrigosKonstantinos en-aut-sei=Syrigos en-aut-mei=Konstantinos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiviLorenzo en-aut-sei=Livi en-aut-mei=Lorenzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PaulusAstrid en-aut-sei=Paulus en-aut-mei=Astrid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimSang-We en-aut-sei=Kim en-aut-mei=Sang-We kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChenYuanbin en-aut-sei=Chen en-aut-mei=Yuanbin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GriesingerFrank en-aut-sei=Griesinger en-aut-mei=Frank kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=ZalcmanGerard en-aut-sei=Zalcman en-aut-mei=Gerard kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HughesBrett G.M. en-aut-sei=Hughes en-aut-mei=Brett G.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=S?rensenJens Benn en-aut-sei=S?rensen en-aut-mei=Jens Benn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=BlaisNormand en-aut-sei=Blais en-aut-mei=Normand kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FerreiraCarlos G.M. en-aut-sei=Ferreira en-aut-mei=Carlos G.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=LindsayColin R. en-aut-sei=Lindsay en-aut-mei=Colin R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DziadziuszkoRafal en-aut-sei=Dziadziuszko en-aut-mei=Rafal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WardPatrick J. en-aut-sei=Ward en-aut-mei=Patrick J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ObiozorCynthia Chinedu en-aut-sei=Obiozor en-aut-mei=Cynthia Chinedu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=WangYang en-aut-sei=Wang en-aut-mei=Yang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=PetersSolange en-aut-sei=Peters en-aut-mei=Solange kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Erasmus MC Cancer Institute, University Medical Center kn-affil= affil-num=2 en-affil=Sotiria General Hospital kn-affil= affil-num=3 en-affil=Department of Biomedical, Experimental and Clinical Sciences gMario Serioh, University of Florence kn-affil= affil-num=4 en-affil=Centre Hospitalier Universitaire de Li?ge kn-affil= affil-num=5 en-affil=Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine kn-affil= affil-num=6 en-affil=The Cancer & Hematology Centers of Western Michigan kn-affil= affil-num=7 en-affil=Medical Oncology Department, Vall dfHebron University Hospital kn-affil= affil-num=8 en-affil=Pius-Hospital Oldenburg kn-affil= affil-num=9 en-affil=Okayama University Hospital kn-affil= affil-num=10 en-affil=Hospital Bichat-Claude Bernard kn-affil= affil-num=11 en-affil=The Prince Charles Hospital, University of Queensland kn-affil= affil-num=12 en-affil=Rigshospitalet kn-affil= affil-num=13 en-affil=Department of Medicine, Centre Hospitalier de lfUniversit? de Montr?al kn-affil= affil-num=14 en-affil=Oncoclinicas kn-affil= affil-num=15 en-affil=Division of Cancer Sciences, University of Manchester and The Christie NHS Foundation Trust kn-affil= affil-num=16 en-affil=University Clinical Centre, Medical University of Gdansk kn-affil= affil-num=17 en-affil=SCRI at OHC kn-affil= affil-num=18 en-affil=Amgen Inc. kn-affil= affil-num=19 en-affil=Amgen Inc. kn-affil= affil-num=20 en-affil=Lausanne University Hospital kn-affil= en-keyword=Brain metastases kn-keyword=Brain metastases en-keyword=KRAS G12C-mutated kn-keyword=KRAS G12C-mutated en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=NSCLC kn-keyword=NSCLC en-keyword=Randomized controlled trial kn-keyword=Randomized controlled trial en-keyword=Sotorasib kn-keyword=Sotorasib en-keyword=Survival kn-keyword=Survival END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=3 article-no= start-page=121 end-page=127 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=Association Between Early Mobilization and Postoperative Pneumonia Following Robot-assisted Minimally Invasive Esophagectomy in Patients with Thoracic Esophageal Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: The objective of this study was to confirm that early mobilization (EM) could reduce pneumonia in patients undergoing robot-assisted minimally invasive esophagectomy (RAMIE) for thoracic esophageal squamous cell carcinoma (TESCC). Methods: Postoperative pneumonia was defined as physician-diagnosed pneumonia using the Esophagectomy Complications Consensus Group definition of pneumonia with a Clavien?Dindo classification grade II?V on postoperative day (POD) 3?5. EM was defined as achieving an ICU Mobility Scale (IMS) ?7 by POD 2. Patients were divided into EM (n = 36) and non-EM (n = 35) groups. Barriers to EM included pain, orthostatic intolerance (OI), and orthostatic hypotension. Results: The overall incidence of postoperative pneumonia was 12.7%, with a significant difference between the EM (2.8%) and non-EM (22.9%) groups (P = 0.014). The odds ratio was 0.098 in the EM group compared to the non-EM group. A significant difference was found between the two groups in terms of the barriers to EM at POD 2 only for OI, with a higher incidence in the non-EM group. Multivariate logistic regression analysis showed that patients with OI were more likely to be unable to achieve EM than those without OI (odds ratio, 7.030; P = 0.006). Conclusion: EM within POD 2 may reduce the incidence of postoperative pneumonia in patients undergoing RAMIE for TESCC. Furthermore, it was suggested that OI can have a negative impact on the EM after RAMIE. en-copyright= kn-copyright= en-aut-name=NOZAWAYasuaki en-aut-sei=NOZAWA en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HARADAKazuhiro en-aut-sei=HARADA en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KATAYAMAYoshimi en-aut-sei=KATAYAMA en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HAMADAMasanori en-aut-sei=HAMADA en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OZAKIToshifumi en-aut-sei=OZAKI en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Physical Medicine and Rehabilitation, Okayama University Hospital kn-affil= affil-num=2 en-affil=Graduate School of Health Science Studies, Kibi International University kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Physical Medicine and Rehabilitation, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Physical Medicine and Rehabilitation, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Physical Medicine and Rehabilitation, Okayama University Hospital kn-affil= en-keyword=Early mobilization kn-keyword=Early mobilization en-keyword=Postoperative pneumonia kn-keyword=Postoperative pneumonia en-keyword=Orthostatic intolerance kn-keyword=Orthostatic intolerance en-keyword=Thoracic esophageal squamous cell carcinoma kn-keyword=Thoracic esophageal squamous cell carcinoma en-keyword=Robot-assisted minimally invasive esophagectomy kn-keyword=Robot-assisted minimally invasive esophagectomy 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=20250802 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Berberine Prevents NSAID-Induced Small Intestinal Injury by Protecting Intestinal Barrier and Inhibiting Inflammasome-Associated Activation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Nonsteroidal anti-inflammatory drugs (NSAID), which are commonly used to manage pain and inflammation, often cause gastrointestinal injuries, including small intestinal damage. Berberine (BBR) is a traditional Chinese medicine that protects against these injuries. However, the mechanism of action is not fully understood.
Aims This study aimed to evaluate the protective effects of BBR against NSAID-induced intestinal injury and elucidate the underlying molecular mechanisms.
Methods We evaluated the effects of BBR on NSAID-induced intestinal injury using a combination of mouse models and human gut organoids. Mice were treated with indomethacin with or without BBR to induce small intestinal injury. Human gut organoids were exposed to NSAID, with or without BBR, to assess their direct epithelial effects. Histological analyses, cytokine measurements, and Western blotting were performed to evaluate intestinal damage, tight junction integrity, and inflammasome-associated activation.
Results In NSAID-treated mice, BBR markedly reduced ulcers and adhesions and preserved ileal Claudin-1, Occludin, and Zonula Occludens-1 (ZO-1) levels. BBR inhibited both NOD-like receptor family pyrin domain-containing 6 and NOD-like receptor family caspase recruitment domain?containing protein 4 inflammasome activation, reducing Caspase-1 maturation and downstream interleukin-1ƒÀ and tumor necrosis factor-ƒ¿ release. In human gut organoids, BBR demonstrated comparable protective effects by directly mitigating NSAID-induced epithelial barrier disruption caused by Claudin-1 and Occludin downregulation, although it did not restore ZO-1 expression.
Conclusions BBR effectively prevented NSAID-induced small intestinal injury by maintaining tight junction integrity and inhibiting inflammasome-associated activation, indicating its potential as a therapeutic agent against such damage. en-copyright= kn-copyright= en-aut-name=IshiguroMikako en-aut-sei=Ishiguro en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyosawaJyunki en-aut-sei=Toyosawa en-aut-mei=Jyunki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=IgawaShoko en-aut-sei=Igawa en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=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, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Nonsteroidal anti-inflammatory drugs-induced small intestinal injury kn-keyword=Nonsteroidal anti-inflammatory drugs-induced small intestinal injury en-keyword=Berberine kn-keyword=Berberine en-keyword=Tight junction protein kn-keyword=Tight junction protein en-keyword=Inflammasomes kn-keyword=Inflammasomes END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250714 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Week 2 remission with vedolizumab as a predictor of long-term remission in patients with ulcerative colitis: a multicenter, retrospective, observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims Vedolizumab (VDZ), a gut-selective monoclonal antibody for ulcerative colitis (UC) treatment, has no established biomarkers or clinical features that predict long-term remission. Week 2 remission, a potential predictor of long-term remission, could inform maintenance treatment strategy.
Methods This retrospective, observational chart review included patients with UC in Japan who initiated VDZ between December 2018 and February 2020. Outcome measures included 14- and 54-week remission rates in patients with week 2 and non-week 2 remission (remission by week 14), 54-week remission rates in patients with week 14 remission and primary nonresponse, and predictive factors of week 2 and week 54 remission (logistic regression).
Results Overall, 332 patients with UC (176 biologic-na?ve and 156 biologic-non-na?ve) were included. Significantly more biologic-na?ve than biologic-non-na?ve patients achieved week 2 remission (36.9% vs. 28.2%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.05?1.94; P=0.0224). Week 54 remission rates were significantly different between week 14 remission and primary nonresponse (both groups: P<0.0001), and between week 2 and non-week 2 remission (all patients: OR, 2.41; 95% CI, 1.30?4.48; P=0.0052; biologic-na?ve patients: OR, 2.40; 95% CI, 1.10?5.24; P=0.0280). Week 2 remission predictors were male sex, no anti-tumor necrosis factor alpha exposure, and normal/mild endoscopic findings. Week 54 remission was significantly associated with week 2 remission and no tacrolimus use.
Conclusions Week 2 remission with VDZ is a predictor of week 54 remission in patients with UC. Week 2 may be used as an evaluation point for UC treatment decisions. (Japanese Registry of Clinical Trials: jRCT-1080225363) en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FernandezJovelle L en-aut-sei=Fernandez en-aut-mei=Jovelle L kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Colitis, ulcerative kn-keyword=Colitis, ulcerative en-keyword=Inflammatory bowel diseases kn-keyword=Inflammatory bowel diseases en-keyword=Japan kn-keyword=Japan en-keyword=Vedolizumab kn-keyword=Vedolizumab END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Factors affecting 1-year persistence with vedolizumab for ulcerative colitis: a multicenter, retrospective real-world study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response.
Methods In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ? 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled.
Results Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00?7.62; P= 0.050) and shorter disease duration (OR for median duration ? 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13?0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response.
Conclusions Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence. en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FernandezJovelle L. en-aut-sei=Fernandez en-aut-mei=Jovelle L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=DeguchiHisato en-aut-sei=Deguchi en-aut-mei=Hisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=22 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Colitis, ulcerative kn-keyword=Colitis, ulcerative en-keyword=Inflammatory bowel diseases kn-keyword=Inflammatory bowel diseases en-keyword=Japan kn-keyword=Japan en-keyword=Vedolizumab kn-keyword=Vedolizumab en-keyword=Medication persistence kn-keyword=Medication persistence END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= 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=Health-related quality of life, work productivity, and persisting challenges in treated ulcerative colitis patients: a Japanese National Health and Wellness Survey en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims Despite available treatments for ulcerative colitis (UC), unmet needs persist among patients in Japan. This study explored the health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), indirect cost, and unmet needs among treated UC patients in Japan.
Methods This cross-sectional, observational study utilized data from the online 2017, 2019, and 2021 Japan National Health and Wellness Survey. Respondents were aged ? 18 years and had undergone or were on UC treatment (5-aminosalicylic acid, steroids, immunomodulators/immunosuppressants, biologics/Janus kinase inhibitors [JAKi]). Demographic, general health, and clinical characteristics, medication adherence, HRQoL, WPAI, and indirect cost were collected and analyzed.
Results Among 293 treated UC patients, 83.6% were non-biologic/JAKi users, 29.0% had UC ? 15 years, 34.8% had moderate-to-severe disease severity, 55.3% experienced ? 1 persisting UC symptom, and 91.5% reported UC as bothersome to an extent. Patients reported EuroQoL visual analog scale score of 68.1 and ? 35% reported anxiety and depression. Mean work productivity loss was 29.3%, resulting in an annual mean indirect loss of 1.1 million JPY (45.3 thousand USD) per person. Higher WPAI (impairment) was associated with being male, moderate-to-severe disease severity, and low treatment adherence (P<0.05). Biologics/JAKi users had higher work impairment, and IM/IS users had higher activity impairment than 5-aminosalicylic acid users (P<0.05).
Conclusions Despite treatment, Japanese UC patients experienced high disease burden and persistent disease-related challenges. Overall HRQoL were lower than the mean healthy population and work productivity impairment led to high indirect costs. The findings suggest the importance of new interventions for optimizing UC outcomes. en-copyright= kn-copyright= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HuangZhezhou en-aut-sei=Huang en-aut-mei=Zhezhou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=QinFei en-aut-sei=Qin en-aut-mei=Fei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Nathan ArokianathanFatima Megala en-aut-sei=Nathan Arokianathan en-aut-mei=Fatima Megala kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Dav?Kiran en-aut-sei=Dav? en-aut-mei=Kiran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShahShweta en-aut-sei=Shah en-aut-mei=Shweta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimHyunchung en-aut-sei=Kim en-aut-mei=Hyunchung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Okayama University kn-affil= affil-num=2 en-affil=Cerner Enviza kn-affil= affil-num=3 en-affil=Cerner Enviza kn-affil= affil-num=4 en-affil=Oracle Life Sciences kn-affil= affil-num=5 en-affil=Bristol Myers Squibb kn-affil= affil-num=6 en-affil=Bristol Myers Squibb kn-affil= affil-num=7 en-affil=Bristol Myers Squibb kn-affil= en-keyword=Quality of life kn-keyword=Quality of life en-keyword=Presenteeism kn-keyword=Presenteeism en-keyword=Absenteeism kn-keyword=Absenteeism en-keyword=Ulcerative colitis kn-keyword=Ulcerative colitis en-keyword=Japan kn-keyword=Japan END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=7 article-no= start-page=920 end-page=927 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=The association of fasting triglyceride variability with renal dysfunction and proteinuria in medical checkup participants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The association between the variability of triglyceride (TG) and chronic kidney disease (CKD) progression remains unclear. We examined whether intraindividual variability in fasting TG was associated with the exacerbation of CKD.
Methods We conducted a retrospective and observational study. 18,339 participants, who went through medical checkups and had checked their estimated glomerular filtration rate (eGFR) and semi-quantitative proteinuria by urine dipstick every year since 2017 for 4 years were registered. Variability in fasting TG was determined using the standard deviation (SD), and maximum minus minimum difference (MMD) between 2017 and 2021. The primary end point for the analysis of eGFR decline was eGFR? Results The renal survival was lower in the higher-SD, and higher-MMD groups than in the lower-SD, and lower-MMD groups, respectively (log-rank test p? Conclusion Fasting TG variability was associated with CKD progression in participants who went through medical checkups. en-copyright= kn-copyright= en-aut-name=Matsuoka-UchiyamaNatsumi en-aut-sei=Matsuoka-Uchiyama en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsakawaTomohiko en-aut-sei=Asakawa en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KatayamaKatsuyoshi en-aut-sei=Katayama en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoShugo en-aut-sei=Okamoto en-aut-mei=Shugo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakemotoRika en-aut-sei=Takemoto en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UmebayashiRyoko en-aut-sei=Umebayashi en-aut-mei=Ryoko 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= 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= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=eGFR decline kn-keyword=eGFR decline en-keyword=Proteinuria kn-keyword=Proteinuria en-keyword=Renal dysfunction kn-keyword=Renal dysfunction en-keyword=Triglyceride variability kn-keyword=Triglyceride variability en-keyword=Fasting triglyceride kn-keyword=Fasting triglyceride END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=1 article-no= start-page=30 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transtibial pullout repair improved short-term clinical outcomes in patients with oblique medial meniscus posterior root tear comparable to radial root tear en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Medial meniscus (MM) posterior root tears (PRT) can lead to excessive knee loading and unsatisfactory clinical outcomes after non-operative treatment or meniscectomy. Although favourable clinical outcomes after MM posterior root (PR) repair have been reported, no study has specifically investigated the outcomes of different types of MMPRT. This study aimed to compare the clinical outcomes of patients with complete radial and oblique MMPRT following MMPR repair.
Methods Forty patients who had undergone MMPR repair were retrospectively investigated. Patients with type 2 (20 knees) and 4 MMPRT (20 knees) were included in this study. The MMPRT type was classified according to the LaPrade classification. Plain radiographs, magnetic resonance images, arthroscopic findings, and pre- and postoperative clinical outcomes were evaluated.
Results At 1 year postoperatively, clinical outcomes notably improved in patients with type 2 and 4 MMPRT. No significant differences were observed in any of the evaluations between these patients, both before and after the surgery.
Conclusion Patients with type 2 and type 4 MMPRT exhibited significantly improved clinical outcomes. MMPR repair is beneficial in treating type 2 and type 4 MMPRT.
Level of evidence IV en-copyright= kn-copyright= en-aut-name=HigashiharaNaohiro en-aut-sei=Higashihara en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FurumatsuTakayuki en-aut-sei=Furumatsu en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkazakiYuki en-aut-sei=Okazaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokoyamaYusuke en-aut-sei=Yokoyama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraMasanori en-aut-sei=Tamura en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawadaKoki en-aut-sei=Kawada en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HasegawaTsubasa en-aut-sei=Hasegawa en-aut-mei=Tsubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoharaToshiki en-aut-sei=Kohara en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Clinical outcomes kn-keyword=Clinical outcomes en-keyword=Medial meniscus kn-keyword=Medial meniscus en-keyword=Oblique tear kn-keyword=Oblique tear en-keyword=Posterior root tear kn-keyword=Posterior root tear en-keyword=Pullout repair kn-keyword=Pullout repair en-keyword=Radial tear kn-keyword=Radial tear END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=305 end-page=309 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Rare Presentation of Pneumonic-Type Adenocarcinoma Hidden behind Empyema en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pneumonic-type adenocarcinoma (P-ADC) can closely mimic pneumonia. We report a P-ADC initially diagnosed as pneumonia which developed into a pulmonary abscess and empyema. A 50-year-old Japanese male diagnosed with pneumonia, pulmonary abscess, and empyema was administered antibiotics and a chest tube for drainage, which improved his symptoms and blood test results. However, chest computed tomography showed an enlarged infiltrative shadow. The patient underwent bronchoscopy and was diagnosed with an adenocarcinoma. This case highlights the importance of considering P-ADC in differential diagnoses when a pneumonia-like shadow enlarges post-empyema treatment. Diagnostic and clinical tests, e.g., bronchoscopy, should be performed in such cases. en-copyright= kn-copyright= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NimanEito en-aut-sei=Niman en-aut-mei=Eito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiRyoko en-aut-sei=Tsuji en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakataKohei en-aut-sei=Takata en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumoriShunsuke en-aut-sei=Matsumori en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MuranoFumika en-aut-sei=Murano en-aut-mei=Fumika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugisakiYuka en-aut-sei=Sugisaki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OmoriHiroki en-aut-sei=Omori en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OmoteRika en-aut-sei=Omote en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=TakahashiKenji en-aut-sei=Takahashi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkadaToshiaki en-aut-sei=Okada en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=10 en-affil=Department of Diagnostic Pathology, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=12 en-affil=Department of General Thoracic Surgery, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center kn-affil= en-keyword=pneumonic type adenocarcinoma kn-keyword=pneumonic type adenocarcinoma en-keyword=empyema kn-keyword=empyema en-keyword=bronchoscopy kn-keyword=bronchoscopy en-keyword=lung cancer diagnosis kn-keyword=lung cancer diagnosis en-keyword=cavity formation kn-keyword=cavity formation END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=283 end-page=286 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anterior Uveitis Secondary to an Infected Postoperative Maxillary Cyst en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 76-year-old man presented with right eyelid swelling and deteriorated vision. Examination revealed anterior uveitis with hypopyon and a visual acuity of 20/2,000 in the right eye, with no abnormalities in the left. Computed tomography revealed enlargement of the right maxillary sinus and internal fluid accumulation, suggesting a postoperative maxillary cyst (POMC). Nasal endoscopic surgery drained the pus by opening the lower wall of the maxillary cyst. Following the procedure, intraocular inflammation resolved, and visual acuity in the right eye improved to 24/20. This is the first reported case of uveitis secondary to POMC. en-copyright= kn-copyright= en-aut-name=ImamuraYuta en-aut-sei=Imamura en-aut-mei=Yuta 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=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KindoHiroya en-aut-sei=Kindo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=MuraiAya en-aut-sei=Murai en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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= affil-num=9 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anterior uveitis kn-keyword=anterior uveitis en-keyword=hypopyon kn-keyword=hypopyon en-keyword=maxillary sinus kn-keyword=maxillary sinus en-keyword=postoperative maxillary cyst kn-keyword=postoperative maxillary cyst END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=279 end-page=282 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-Term Survival Following Extended Cholecystectomy for Synchronous Gallbladder and Regional Lymph Node Metastasis of Lung Adenocarcinoma, with Subsequent Pulmonary Lobectomy en-subtitle= kn-subtitle= en-abstract= kn-abstract=An 80-year-old male underwent an extended cholecystectomy for node-positive gallbladder adenocarcinoma. Two weeks later, hemoptysis revealed a left hilar tumor obstructing the bronchus, which was diagnosed as adenocarcinoma. Three months post-cholecystectomy, a left upper pulmonary lobectomy was performed. Histological similarity and positive thyroid transcription factor-1 (TTF-1) immunostaining in both tumors confirmed lung adenocarcinoma with gallbladder metastasis. Despite the generally poor prognosis for gallbladder metastasis from lung cancer, the patient achieved 3 years of survival. Patients with isolated synchronous gallbladder metastasis from lung cancer may benefit from oligometastasectomy. en-copyright= kn-copyright= en-aut-name=YoshikawaMao en-aut-sei=Yoshikawa en-aut-mei=Mao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaoHiroyuki en-aut-sei=Tao en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Japanese Red Cross Society Himeji Hospital kn-affil= en-keyword=gallbladder metastasis kn-keyword=gallbladder metastasis en-keyword=lung cancer kn-keyword=lung cancer en-keyword=oligometastatic disease kn-keyword=oligometastatic disease END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=4 article-no= start-page=231 end-page=242 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bloodstream Infections Caused by Gram-Negative Bacteria in Geriatric Patients: Epidemiology, Antimicrobial Resistance and The Factors Affecting Mortality en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bloodstream infections (BSIs) are an important cause of morbidity and mortality in geriatric patients. We retrospectively analyzed the cases of geriatric patients who developed BSIs due to gram-negative bacteria in order to evaluate the epidemiology, antimicrobial resistance, and the factors affecting mortality. The cases of 110 patients aged ? 65 years admitted to our hospital between January 1, 2017, and December 31, 2022 were assessed; 70 (63.6%) of the BSIs were healthcare-associated BSIs. The urinary system was the most common detectable source of infection at 43.6%. The most frequently isolated bacteria were Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, in that order. Carbapenem resistance was detected in 17 patients (15.5%), and extended-spectrum beta-lactamase (ESBL) production from Enterobacterales family members was detected in 37 (51.4%) patients. Multivariate analysis revealed that (i) the probability of mortality in the patients with total bilirubin was increased by approx. sixfold and (ii) the likelihood of mortality for those with a Pitt bacteremia score (PBS) ? 4 points was approx. 17 times higher. PBS and simplified qPitt scores can help predict mortality and manage geriatric patients. There is a significant increase in mortality among patients with procalcitonin (PCT) levels at ? 2 nm/ml. en-copyright= kn-copyright= en-aut-name=KardanM Enes en-aut-sei=Kardan en-aut-mei=M Enes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ErdemIlknur en-aut-sei=Erdem en-aut-mei=Ilknur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YildizEmre en-aut-sei=Yildiz en-aut-mei=Emre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KirazNuri en-aut-sei=Kiraz en-aut-mei=Nuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=?elikkolAliye en-aut-sei=?elikkol en-aut-mei=Aliye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Faculty of Medicine, Namik Kemal University kn-affil= affil-num=4 en-affil=Department of Medical Microbiology, Faculty of Medicine, Namik Kemal University kn-affil= affil-num=5 en-affil=Department of Biochemistry, Faculty of Medicine, Namik Kemal University kn-affil= en-keyword=geriatrics kn-keyword=geriatrics en-keyword=gram-negative bacteria kn-keyword=gram-negative bacteria en-keyword=epidemiology kn-keyword=epidemiology en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=mortality kn-keyword=mortality END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=1 article-no= start-page=e70005 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=Lyme neuroborreliosis in Japan: Borrelia burgdorferi sensu lato as a cause of meningitis of previously undetermined etiology in hospitalized patients outside of the island of Hokkaido, 2010?2021 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Purpose: Clinical manifestations of Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), include erythema migrans, Lyme neuroborreliosis (LNB), carditis, and arthritis. LB is a notifiable disease in Japan with <30 surveillance-reported LB cases annually, predominately from Hokkaido Prefecture. However, LB, including LNB, may be under-diagnosed in Japan since diagnostic tests are not readily available. We sought to determine if LNB could be a cause of previously undiagnosed encephalitis or meningitis in Japan.
Methods: Investigators at 15 hospitals in 10 prefectures throughout Japan retrieved serum and/or cerebrospinal fluid (CSF) samples collected in 2010?2021 from 517 patients hospitalized with encephalitis or meningitis which had an etiology that had not been determined. Samples were tested for Bbsl-specific antibodies using ELISA and Western blot tests. In alignment with the European Union LNB case definition, a confirmed LNB case had CSF pleocytosis and intrathecal production of Bbsl-specific antibodies and a probable LNB case had a CSF sample with pleocytosis and Bbsl-specific antibodies.
Results: LNB was identified in three hospitalized patients with meningitis of previously undetermined etiology: a male resident of Aomori Prefecture was a confirmed LNB case, and two female residents of Oita Prefecture were probable LNB cases. None of the patients with confirmed or probable LNB had traveled in the month prior to symptom onset and none had samples previously tested for LB.
Conclusion: The identification of previously undiagnosed LNB cases indicates a need for enhanced disease awareness in Japan, particularly beyond Hokkaido Island, and more readily available LB diagnostic testing. en-copyright= kn-copyright= en-aut-name=OhiraMasayuki en-aut-sei=Ohira en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakanoAi en-aut-sei=Takano en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshiKentaro en-aut-sei=Yoshi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AraiAkira en-aut-sei=Arai en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsoYashuhiro en-aut-sei=Aso en-aut-mei=Yashuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FurutaniRikiya en-aut-sei=Furutani en-aut-mei=Rikiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamanoTadanori en-aut-sei=Hamano en-aut-mei=Tadanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Takahashi]IwataIkuko en-aut-sei=Takahashi]Iwata en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KanekoChikako en-aut-sei=Kaneko en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuuraTohru en-aut-sei=Matsuura en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaNorihisa en-aut-sei=Maeda en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakajimaHideto en-aut-sei=Nakajima en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShindoKatsuro en-aut-sei=Shindo en-aut-mei=Katsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SuenagaToshihiko en-aut-sei=Suenaga en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SugieKazuma en-aut-sei=Sugie en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SuzukiYasuhiro en-aut-sei=Suzuki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=AnguloFrederick J. en-aut-sei=Angulo en-aut-mei=Frederick J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=EdwardsJuanita en-aut-sei=Edwards en-aut-mei=Juanita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=BenderCody Matthew en-aut-sei=Bender en-aut-mei=Cody Matthew kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HarperLisa R. en-aut-sei=Harper en-aut-mei=Lisa R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=NakayamaYoshikazu en-aut-sei=Nakayama en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ItoShuhei en-aut-sei=Ito en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=PilzAndreas en-aut-sei=Pilz en-aut-mei=Andreas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=StarkJames H. en-aut-sei=Stark en-aut-mei=James H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=Mo?siJennifer C. en-aut-sei=Mo?si en-aut-mei=Jennifer C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MizusawaHidehiro en-aut-sei=Mizusawa en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TakaoMasaki en-aut-sei=Takao en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory and Internal Medicine, National Center of Neurology and Psychiatry kn-affil= affil-num=2 en-affil=Department of Veterinary Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University kn-affil= affil-num=3 en-affil=National Research Center for the Control and Prevention of Infectious Diseases, Nagasaki University kn-affil= affil-num=4 en-affil=Department of Neurology, Aomori Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Neurology, Oita Prefectural Hospital kn-affil= affil-num=6 en-affil=Department of Neurology, National Hospital Organization, Shinshu Ueda General Hospital kn-affil= affil-num=7 en-affil=Department of Neurology, University of Fukui Hospital kn-affil= affil-num=8 en-affil=Department of Neurology, Hokkaido University Hospital kn-affil= affil-num=9 en-affil=Department of Neurology, Southern Tohoku General Hospital kn-affil= affil-num=10 en-affil=Division of Neurology, Jichi Medical University kn-affil= affil-num=11 en-affil=Department of Neurology, National Hospital Organization Beppu Medical Center kn-affil= affil-num=12 en-affil=Department of Neurology, Nihon University Itabashi Hospital kn-affil= affil-num=13 en-affil=Department of Neurology, Kurashiki Central Hospital kn-affil= affil-num=14 en-affil=Department of Neurology, Tenri Hospital kn-affil= affil-num=15 en-affil=Department of Neurology, Nara Medical University Hospital kn-affil= affil-num=16 en-affil=Department of Neurology, National Hospital Organization Asahikawa Medical Center kn-affil= affil-num=17 en-affil=Department of Neurology, Okayama University Hospital kn-affil= affil-num=18 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=19 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=20 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=21 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=22 en-affil=Vaccines Medical Affairs, Pfizer Japan Inc kn-affil= affil-num=23 en-affil=Vaccines Medical Affairs, Pfizer Japan Inc kn-affil= affil-num=24 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=25 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=26 en-affil=Vaccines and Antivirals Medical Affairs, Pfizer Vaccines kn-affil= affil-num=27 en-affil=Department of Neurology, National Center of Neurology and Psychiatry kn-affil= affil-num=28 en-affil=Department of Clinical Laboratory and Internal Medicine, National Center of Neurology and Psychiatry kn-affil= en-keyword=epidemiology kn-keyword=epidemiology en-keyword=disease burden kn-keyword=disease burden en-keyword=Lyme neuroborreliosis kn-keyword=Lyme neuroborreliosis en-keyword=meningitis kn-keyword=meningitis en-keyword=tick-borne disease kn-keyword=tick-borne disease END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=1 article-no= start-page=104318 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=Hypotheses of pathophysiological mechanisms in epileptic encephalopathies: A review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Epileptic encephalopathy (EE) is a serious clinical issue that manifests as part of developmental and epileptic encephalopathy (DEE), particularly in childhood epilepsy. In EE, neurocognitive functions and behavior are impaired by intense epileptiform electroencephalogram (EEG) activity. Hypotheses of pathophysiological mechanisms behind EE are reviewed to contribute to an effective solution for EE.
Review: Current hypotheses are as follows: 1) neuronal dysfunction based on genetic abnormalities that may affect neurocognitive functions and epilepsy separately; 2) impairment of synaptic homeostasis during sleep that may be responsible for DEE/EE with spike-and-wave activation in sleep; 3) abnormal subcortical regulation of the cerebral cortex; 4) abnormal cortical metabolism and hemodynamics with impairment of the neural network including default mode network; 5) neurotransmitter imbalance and disordered neural excitability; 6) the effects of neuroinflammation that may be caused by epileptic seizures and in turn aggravate epileptogenesis; 7) the interaction between physiological and pathological high-frequency EEG activity; etc. The causal relationship between epileptiform EEG activity and neurocognitive dysfunctions is small in DEE based on genetic abnormalities and it is largely unestablished in the other hypothetical mechanisms.
Conclusion: We have not yet found answers to the question of whether the single-central or multiple derangements are present and what seizures and intense epileptiform EEG abnormalities mean in EE. We need to continue our best efforts in both aspects to elucidate the pathophysiological mechanisms of DEE/EE and further develop epilepsy treatment and precision medicine. en-copyright= kn-copyright= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShibataTakashi en-aut-sei=Shibata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchiyaHiroki en-aut-sei=Tsuchiya en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkiyamaMari en-aut-sei=Akiyama en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Pediatrics, Asahigawaso Rehabilitation and Medical Center kn-affil= affil-num=2 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pediatric Neurology, Okayama University Hospital and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Behavior kn-keyword=Behavior en-keyword=Childhood epilepsy kn-keyword=Childhood epilepsy en-keyword=Cognitive function kn-keyword=Cognitive function en-keyword=Developmental and epileptic encephalopathy kn-keyword=Developmental and epileptic encephalopathy en-keyword=Regression kn-keyword=Regression END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=30648 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the maturation of the cardiomyocytes. This study aimed to improve the differentiation and subsequent maturation of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunocytochemistry, transmission electron microscopy, calcium imaging and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and MYL2) in both groups, with higher protein expression in the stretch group. Additionally, structural maturation of iPS-CMs in the stretch group was notably better than in the control group. A significant increase in the contractility and calcium cycle of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturation of iPS-CMs co-cultured with HGF. en-copyright= kn-copyright= en-aut-name=WangMengxue en-aut-sei=Wang en-aut-mei=Mengxue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IdeiHarumi en-aut-sei=Idei en-aut-mei=Harumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangChen en-aut-sei=Wang en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiangYin en-aut-sei=Liang en-aut-mei=Yin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiuYun en-aut-sei=Liu en-aut-mei=Yun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsudaYusuke en-aut-sei=Matsuda en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nursing, School of Life and Health Sciences, HuZhou College kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Human induced pluripotent stem cell kn-keyword=Human induced pluripotent stem cell en-keyword=Cardiomyocyte kn-keyword=Cardiomyocyte en-keyword=Human gingival fibroblast kn-keyword=Human gingival fibroblast en-keyword=Mechanical stretching kn-keyword=Mechanical stretching END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=16 article-no= start-page=7832 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synergistic Antimicrobial Activity of BrSPR20-P1 Peptide and Silver Nanoparticles Against Pathogenic Bacteria en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bacterial infection is a cause of life-threatening diseases. The emergence of antimicrobial-resistant bacteria exacerbates this situation, highlighting the need for the discovery of new antimicrobial agents. Our previous study identified a novel antimicrobial peptide, BrSPR20-P1 (P1), which showed potential activity against MRSA. Additionally, silver nanoparticles (AgNPs) exhibit broad-spectrum antibacterial activity, capable of killing multidrug-resistant bacteria. The combination of antimicrobial agents presents a novel strategy for combating these pathogens. This study aimed to evaluate the antibacterial activity of the combination of P1 and AgNPs. It revealed that the combinations showed synergy. The P1 and AgNP mixture at a concentration of 1 and 8 ?g/mL (1:8) doubled the activity against S. aureus and MRSA, while that combination of 64 and 64 ?g/mL (64:64) exhibited broad-spectrum activity, expanding to E. coli with a 32-fold increase. These combinations exhibited a bactericidal effect, showing the rapid killing of tested bacteria at 10~ MIC, with killing rates during the first 3 h ranging from 4.04 } 0.01 to 4.31 } 0.03 h?1. The P1 and AgNP mixtures caused a low risk of antibacterial resistance up to 30 passages. It was demonstrated that the synergistic activity of P1 and AgNPs occurred through the disruption of cell walls and membranes, leakage of intracellular materials, and cell lysis. Additionally, the mixtures appeared to interact with bacterial genomic DNA, as indicated by a gel retardation assay. These activities of the combinations were concentration-dependent. The 1:8 ?g/mL mixture caused low hemolysis and cytotoxicity and did not impede the wound healing process. In contrast, although the 64:64 ?g/mL mixture showed excellent antibacterial efficacy, it was toxic to erythrocytes and mammalian cells. It implies that dose optimization is required to balance its efficacy and toxicity. Therefore, the P1 and AgNP combinations exhibit synergistic antimicrobial activity and have the potential to resolve bacterial infections. en-copyright= kn-copyright= en-aut-name=ThonginThanyamai en-aut-sei=Thongin en-aut-mei=Thanyamai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawatdeeSomchai en-aut-sei=Sawatdee en-aut-mei=Somchai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SongnakaNuttapon en-aut-sei=Songnaka en-aut-mei=Nuttapon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WiwasukuTheanchai en-aut-sei=Wiwasuku en-aut-mei=Theanchai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SrichanaTeerapol en-aut-sei=Srichana en-aut-mei=Teerapol kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakphengTitpawan en-aut-sei=Nakpheng en-aut-mei=Titpawan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AtipairinApichart en-aut-sei=Atipairin en-aut-mei=Apichart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= School of Pharmacy, Walailak University kn-affil= affil-num=2 en-affil= School of Pharmacy, Walailak University kn-affil= affil-num=3 en-affil= School of Pharmacy, Walailak University kn-affil= affil-num=4 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=School of Science, Walailak University kn-affil= affil-num=6 en-affil=Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University kn-affil= affil-num=7 en-affil=Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University kn-affil= affil-num=8 en-affil= School of Pharmacy, Walailak University kn-affil= en-keyword=antimicrobial peptide kn-keyword=antimicrobial peptide en-keyword=Brevibacillus sp. SPR20 kn-keyword=Brevibacillus sp. SPR20 en-keyword=silver nanoparticle kn-keyword=silver nanoparticle en-keyword=synergistic effect kn-keyword=synergistic effect END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=7 article-no= start-page=e70506 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250626 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tongue Schwannoma at the Median Inferior Surface in the Elderly: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report the extremely rare case of an atypical schwannoma that occurred at the median inferior surface of the tongue in an elderly patient. We performed an excisional biopsy to achieve a definitive diagnosis. Based on the histopathological findings, we diagnosed a schwannoma (mixed type, Antoni A/B). en-copyright= kn-copyright= en-aut-name=FukushimaKiho en-aut-sei=Fukushima en-aut-mei=Kiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoIzumi en-aut-sei=Yamamoto en-aut-mei=Izumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YutoriHirokazu en-aut-sei=Yutori en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=elderly kn-keyword=elderly en-keyword=inferior surface of the tongue kn-keyword=inferior surface of the tongue en-keyword=schwannoma kn-keyword=schwannoma en-keyword=tongue tumor kn-keyword=tongue tumor END start-ver=1.4 cd-journal=joma no-vol=104 cd-vols= no-issue=2 article-no= start-page=151495 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=Tri-culture model of intestinal epithelial cell, macrophage, and bacteria for the triggering of inflammatory bowel disease on a microfluidic device en-subtitle= kn-subtitle= en-abstract= kn-abstract=Inflammatory bowel disease (IBD) involves gastrointestinal inflammation, due to intestinal epithelial barrier destruction caused by excessive immune activation. Conventional cell culture systems do not provide a model system that can recapitulate the complex interactions between epithelial cells, immune cells, and intestinal bacteria. To address this, we developed a microfluidic device that mimics the inflammatory response associated with microbial invasion of the intestinal mucosa. The device consisted of two media channels, an upper and a lower channel, and a porous membrane between these channels on which C2BBe1 intestinal epithelial cells were seeded to form a tight junction layer. Each electrode was placed in contact with both channels to continuously monitor the tight junction state. Fresh medium flow allowed bacterial numbers to be controlled and bacterial toxins to be removed, allowing co-culture of mammalian cells and bacteria. In addition, RAW264 macrophage cells were attached to the bottom of the lower channel. By introducing E. coli into the lower channel, the RAW264 cells were activated and produced TNF-ƒ¿, successfully recapitulating a culture model of inflammation in which the C2BBe1cell tight junction layer was destroyed. The main structure of the device was initially made of polydimethylsiloxane to facilitate its widespread use, but with a view to introducing anaerobic bacteria in the future, a similar phenomenon was successfully reproduced using polystyrene. When TPCA-1, an IƒÈB kinase 2 inhibitor was added into this IBD culture model, the tight junction destruction was significantly suppressed. The results suggest that this IBD culture model also is useful as a screening system for anti-IBD drugs. en-copyright= kn-copyright= en-aut-name=TamuraShiori en-aut-sei=Tamura en-aut-mei=Shiori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PasangClarissa Ellice Talitha en-aut-sei=Pasang en-aut-mei=Clarissa Ellice Talitha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsudaMinami en-aut-sei=Tsuda en-aut-mei=Minami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaShilan en-aut-sei=Ma en-aut-mei=Shilan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShindoHiromasa en-aut-sei=Shindo en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhkuboTomoki en-aut-sei=Ohkubo en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiyamaYoichi en-aut-sei=Fujiyama en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TamaiMiho en-aut-sei=Tamai en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TagawaYoh-ichi en-aut-sei=Tagawa en-aut-mei=Yoh-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=2 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=3 en-affil=School of Life Science and Technology, Tokyo Institute of Technology 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, Tokyo Institute of Technology kn-affil= affil-num=6 en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Biology-Chemistry Unit, Technology Research Laboratory, Shimadzu Corporation kn-affil= affil-num=8 en-affil=Biology-Chemistry Unit, Technology Research Laboratory, Shimadzu Corporation kn-affil= affil-num=9 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=10 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= en-keyword=Intestine chip kn-keyword=Intestine chip en-keyword=Inflammatory bowel disease kn-keyword=Inflammatory bowel disease en-keyword=Co-culture kn-keyword=Co-culture en-keyword=Tri-culture kn-keyword=Tri-culture en-keyword=Fluidic device kn-keyword=Fluidic device en-keyword=Disease model kn-keyword=Disease model en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Inflammation kn-keyword=Inflammation END start-ver=1.4 cd-journal=joma no-vol=272 cd-vols= no-issue=1 article-no= start-page=36 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genetic and functional analyses of SPTLC1 in juvenile amyotrophic lateral sclerosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. Pathogenic variants in SPTLC1, encoding a subunit of serine palmitoyltransferase, cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), and have recently been associated with juvenile ALS. SPTLC1 variants associated with ALS cause elevated levels of sphinganines and ceramides. Reports on ALS associated with SPTLC1 remain limited. This study aimed to investigate the frequency of SPTLC1 variants in ALS and relevant clinical characteristics.
Methods We analyzed whole-exome and whole-genome sequence data from 40 probands with familial ALS and 413 patients with sporadic ALS without previously identified causative variants. Reverse transcription polymerase chain reaction (RT-PCR) analysis and droplet digital PCR (ddPCR) were used to assess splicing and mosaicism, respectively. Plasma sphingolipid levels were quantified to analyze biochemical consequences.
Results The heterozygous c.58G>A, p.Ala20Thr variant was identified in a 21-year-old Japanese female patient presenting with symmetric weakness which slowly progressed over 15 years. RT-PCR analysis showed no splice defects. Plasma sphingolipid levels in the patient were significantly increased compared to her asymptomatic parents. ddPCR revealed that the asymptomatic father harbored a mosaic variant with 17% relative mutant allele abundance in peripheral blood leukocytes.
Conclusions We identified a pathogenic c.58G>A, p.Ala20Thr SPTLC1 variant in a patient with juvenile ALS, likely inherited from an asymptomatic parent with mosaicism. Lipid analysis results are consistent with previous findings on SPTLC1-associated ALS. Further studies are necessary to determine the clinical effect of mosaic variants of SPTLC1. en-copyright= kn-copyright= en-aut-name=OkuboSo en-aut-sei=Okubo en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaruseHiroya en-aut-sei=Naruse en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=SudoAtsushi en-aut-sei=Sudo en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EsakiKayoko en-aut-sei=Esaki en-aut-mei=Kayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatakeWataru en-aut-sei=Satake en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GreimelPeter en-aut-sei=Greimel en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShingaiNanoka en-aut-sei=Shingai en-aut-mei=Nanoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OyaYasushi en-aut-sei=Oya en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshikawaTakeo en-aut-sei=Yoshikawa en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Biotechnology and Life Sciences, Faculty of Biotechnology and Life Sciences, Sojo University kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Laboratory for Cell Function Dynamics, RIKEN Centre for Brain Sciences kn-affil= affil-num=10 en-affil=Division of Applied Life Science, Graduate School of Engineering, Sojo University kn-affil= affil-num=11 en-affil=Department of Neurology, National Center of Neurology and Psychiatry kn-affil= affil-num=12 en-affil=Laboratory of Molecular Psychiatry, RIKEN Center for Brain Science kn-affil= affil-num=13 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=Juvenile amyotrophic lateral sclerosis kn-keyword=Juvenile amyotrophic lateral sclerosis en-keyword=SPTLC1 kn-keyword=SPTLC1 en-keyword=Sphingolipids kn-keyword=Sphingolipids en-keyword=Mosaicism kn-keyword=Mosaicism END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=14 article-no= start-page=2240 end-page=2244 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Wilson's Disease Preceded by Schizophrenia-like Symptoms with Frontal-dominant Leukoencephalopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=We herein report a 26-year-old man diagnosed with Wilson's disease (WD), initially treated for schizophrenia for 11 years. At 26 years old, he was admitted because of status epilepticus. Brain magnetic resonance imaging revealed frontal-dominant leukoencephalopathy with cystic changes and basal ganglia atrophy. The diagnosis of WD was confirmed based on neuropsychiatric symptoms, Kayser-Fleischer rings, abnormal copper metabolism, and a genetic analysis of ATP7B. Psychotic symptoms in WD can precede neurological manifestations, and extrapyramidal signs may be mistaken for drug-induced Parkinsonism. WD should be considered in patients presenting with progressive Parkinsonism preceded by schizophrenia-like psychiatric symptoms. en-copyright= kn-copyright= en-aut-name=MiyanoRyoji en-aut-sei=Miyano en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ObataSatomi en-aut-sei=Obata en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KoyamaHiroaki en-aut-sei=Koyama en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakaiYudai en-aut-sei=Nakai en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KubotaAkatsuki en-aut-sei=Kubota en-aut-mei=Akatsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimizuJun en-aut-sei=Shimizu en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakuishiKaori en-aut-sei=Sakuishi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=Wilsonfs disease kn-keyword=Wilsonfs disease en-keyword=leukoencephalopathy kn-keyword=leukoencephalopathy en-keyword=brain MRI kn-keyword=brain MRI en-keyword=ATP7B kn-keyword=ATP7B en-keyword=schizophrenia kn-keyword=schizophrenia END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=15 article-no= start-page=e71098 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real]World Data of Comprehensive Cancer Genomic Profiling Tests Performed in the Routine Clinical Setting in Sarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Next-generation sequencing-based comprehensive cancer genomic profiling (CGP) tests are beneficial for refining diagnosis and personalized treatment of various cancers. However, the clinical impact of CGP, as covered by public health insurance in the management of sarcomas, remains unknown. Especially, the data on the utility of the newly emerging dual DNA?RNA panel compared to the conventional DNA-only panel in clinical settings is lacking. Therefore, we evaluated the utility of CGP in routine clinical practice for sarcoma treatment.
Patients and Methods: In this study, three types of DNA panel and one DNA?RNA panel, reimbursed by Japanese public health insurance, were utilized. We detected oncogenic and druggable gene mutations and genotype-matched therapies.
Results: One hundred and thirty-six patients were included in this study. Based on the detection of highly histology-specific translocations in the sequencing results, 2.2% of patients were re-classified. In patients with translocation-related sarcomas, a DNA?RNA panel identified more histology-specific fusion genes than DNA panels (p?=?0.0035). Specifically, 86.8% and 39.0% of patients had oncogenic and druggable genomic alterations, respectively. Of these, 9.6% underwent genotype-matched therapy, with a 36.3% response rate and an 81.8% disease control rate. Patients who were administered genomically matched therapy had better overall survival (OS) than those who did not in patients with metastatic or advanced sarcoma with no prior chemotherapy (3-year OS: 83.3% vs. 48.0%, p?=?0.42). Patients with TP53 and RB1 mutations had worse OS than those without. Germline findings were detected in 11.0% of the patients, one of whom had a truly germline origin.
Conclusions: This study suggests that publicly reimbursed CGP tests, particularly the dual DNA?RNA panel, could be beneficial for refining diagnostic precision in selected sarcoma subtypes, treatment decisions, detecting the germline findings, and prognosis prediction in routine clinical settings for sarcoma. The implementation of genotype-matched therapies showed favorable clinical outcomes and improved the prognosis. en-copyright= kn-copyright= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=OsoneTatsunori en-aut-sei=Osone en-aut-mei=Tatsunori 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=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=FutagawaMashu en-aut-sei=Futagawa en-aut-mei=Mashu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShimoiTatsunori en-aut-sei=Shimoi en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 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=15 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=16 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=17 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Medical Oncology, National Cancer Center Hospital kn-affil= affil-num=13 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Center for Clinical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=genotype-matched therapy kn-keyword=genotype-matched therapy en-keyword=multiplex gene panel test kn-keyword=multiplex gene panel test en-keyword=sarcoma kn-keyword=sarcoma 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=20250613 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distinct age-related effects of homologous recombination deficiency on genomic profiling and treatment efficacy in gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The incidence of gastric cancer among younger patients is increasing globally, with growing attention being paid to the role of homologous recombination deficiency (HRD). However, the effect of HRD on treatment outcomes and prognosis in this population remains unclear.
Methods We analyzed clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics database. Younger patients (??39 years, n?=?140) were compared with older patients (??65 years, n?=?1118) diagnosed with gastric cancer. This study focused on mutations in homologous recombination repair (HRR) genes and their association with tumor mutation burden (TMB), microsatellite instability (MSI), and treatment outcomes.
Results In older patients, HRD was associated with higher TMB and microsatellite instability-high (MSI-H) status, whereas no such correlations were observed in younger patients. Notably, MSI-H status was not observed in the younger group. Younger patients with HRD had a significantly shorter time to treatment failure (TTF) and overall survival (OS) than those without HRD. Conversely, in older patients, there was no significant difference in TTF or OS based on HRD status.
Conclusion HRR gene mutations influence genomic profiling, TMB, and MSI differently depending on the age of gastric cancer onset, suggesting potential effects on treatment efficacy and prognosis. en-copyright= kn-copyright= en-aut-name=MakiYoshie en-aut-sei=Maki en-aut-mei=Yoshie 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=OzatoToshiki en-aut-sei=Ozato en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 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=7 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=8 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=9 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=10 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=11 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=12 ORCID= affil-num=1 en-affil=Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Clinical Genomic Medicine, 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=Center for Comprehensive 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=Faculty of Medicine, Department of Practical Gastrointestinal Endoscopy, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Faculty of Medicine, Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Homologous recombination repair gene kn-keyword=Homologous recombination repair gene en-keyword=Early-onset gastric cancer kn-keyword=Early-onset gastric cancer en-keyword=Comprehensive genomic profiling kn-keyword=Comprehensive genomic profiling END start-ver=1.4 cd-journal=joma no-vol=638 cd-vols= no-issue=8049 article-no= start-page=225 end-page=236 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=Immune evasion through mitochondrial transfer in the tumour microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T?cell attack1. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses2,3,4. However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement. T?cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation. This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies. en-copyright= kn-copyright= en-aut-name=IkedaHideki en-aut-sei=Ikeda en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeTomofumi en-aut-sei=Watanabe en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakenagaKeizo en-aut-sei=Takenaga en-aut-mei=Keizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=AkiSho en-aut-sei=Aki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LinJason en-aut-sei=Lin en-aut-mei=Jason kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 ORCID= en-aut-name=SuzukiShinichiro en-aut-sei=Suzuki en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MakinoshimaHideki en-aut-sei=Makinoshima en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItamiMakiko en-aut-sei=Itami en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakamuraYuki en-aut-sei=Nakamura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TatsumiYasutoshi en-aut-sei=Tatsumi en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SuenagaYusuke en-aut-sei=Suenaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MorinagaTakao en-aut-sei=Morinaga en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 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=20 ORCID= en-aut-name=OhnumaTakehiro en-aut-sei=Ohnuma en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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=22 ORCID= en-aut-name=UmedaYoshiyasu en-aut-sei=Umeda en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 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=24 ORCID= en-aut-name=KiniwaYukiko en-aut-sei=Kiniwa en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 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=26 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=27 ORCID= en-aut-name=IkedaJun-ichiro en-aut-sei=Ikeda en-aut-mei=Jun-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=HanazawaToyoyuki en-aut-sei=Hanazawa en-aut-mei=Toyoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=SuzukiTakuji en-aut-sei=Suzuki en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=OsawaTsuyoshi en-aut-sei=Osawa en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 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=34 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=35 ORCID= affil-num=1 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=2 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute 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 Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute kn-affil= affil-num=6 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute 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=Division of Nutriomics and Oncology, RCAST, The University of Tokyo kn-affil= affil-num=9 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=10 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan Department of Dermatology, Graduate School of Medicine, Chiba University kn-affil= affil-num=11 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Tsuruoka Metabolomics Laboratory, National Cancer Center kn-affil= affil-num=15 en-affil=Department of Surgical Pathology, Chiba Cancer Center kn-affil= affil-num=16 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=18 en-affil=Laboratory of Evolutionary Oncology, Chiba Cancer Center Research Institute kn-affil= affil-num=19 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=20 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=21 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=22 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=23 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=24 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=25 en-affil=Department of Dermatology, Shinshu University School of Medicine kn-affil= affil-num=26 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=27 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=28 en-affil=Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University kn-affil= affil-num=29 en-affil=Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine kn-affil= affil-num=30 en-affil=Department of General Thoracic Surgery and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=31 en-affil=Division of Cellular Signalling, National Cancer Center Research Institute kn-affil= affil-num=32 en-affil=Department of Respirology, Graduate School of Medicine, Chiba University kn-affil= affil-num=33 en-affil=Division of Nutriomics and Oncology, RCAST, The University of Tokyo kn-affil= affil-num=34 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=35 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=17 cd-vols= no-issue= article-no= start-page=1477 end-page=1486 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predictive Value of Tumor ERCC1 Expression for Treatment Outcomes After Adjuvant Chemotherapy in Patients with Completely Resected Non-Small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To evaluate the predictive value of tumor expression of the excision repair cross-complementation group 1 gene (ERCC1) for the treatment outcomes after platinum-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC).
Methods: In this study, we conducted immunohistochemical analysis using a mouse monoclonal anti-ERCC1 antibody (clone 8F1) of operative specimens obtained from 238 patients enrolled in the SLCG0401 study which compared paclitaxel plus carboplatin (CBDCA+PTX) with uracil-tegafur (UFT) as adjuvant chemotherapy for stage IB-IIIA NSCLC. The overall survival (OS) of the patients was compared according to the ERCC1 expression status and adjuvant chemotherapy employed.
Results: Of the 238 specimens, 102 (42.9%) showed a positive result for ERCC1 expression. There were no significant differences in the patient characteristics or OS between the tumor ERCC1-positive and -negative patient groups. Among the patients with ERCC1-negative tumors, there was no significant difference in the survival between patient groups treated with CBDCA+PTX and UFT (HR=0.932, 95% CI: 0.52? 1.67, p=0.814). However, among the patients with ERCC1-positive tumors, CBDCA+PTX treatment tended to yield an inferior outcome, in terms of the OS, as compared with UFT treatment (HR=1.852, 95% CI: 0.92? 3.73, p=0.080). Multivariate analysis showed that ERCC1 expression was not an independent predictor of the OS following CBDCA+PTX treatment in completely resected NSCLC patients.
Conclusion: In completely resected NSCLC patients with positive tumor ERCC1 expression, adjuvant CBDCA+PTX treatment tended to yield an inferior outcome as compared with UFT treatment in terms of the OS. However, immunohistochemical analysis with the 8F1 antibody cannot be used for clinical decision making at this point. en-copyright= kn-copyright= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaishoShinsuke en-aut-sei=Saisho en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkumuraNorihito en-aut-sei=Okumura en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraHiroshige en-aut-sei=Nakamura en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=5 en-affil=Division of General Thoracic Surgery and Breast and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Tottori University kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Kyoto University Graduate School of Medicine kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=postoperative adjuvant chemotherapy kn-keyword=postoperative adjuvant chemotherapy en-keyword=platinum-based chemotherapy kn-keyword=platinum-based chemotherapy en-keyword=excision repair crosscomplementation group 1 gene kn-keyword=excision repair crosscomplementation group 1 gene en-keyword=survival kn-keyword=survival END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=cr.25-0262 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=A Case of Omental Bleeding as a Result of Segmental Arterial Mediolysis Treated Successfully by Laparoscopic Partial Omentectomy en-subtitle= kn-subtitle= en-abstract= kn-abstract=INTRODUCTION: Segmental arterial mediolysis (SAM) is a rare, non-atherosclerotic, non-inflammatory arteriopathy characterized by lysis of the arterial media, leading to aneurysm formation and possible rupture. Although visceral arteries are typically involved, SAM-induced omental bleeding is extremely uncommon. While transcatheter arterial embolization (TAE) has been reported, surgical resection offers both definitive hemostasis and histopathological confirmation.
CASE PRESENTATION: A 56-year-old man presented with upper abdominal pain without a history of trauma. Contrast-enhanced CT revealed a hematoma and fusiform dilation of an omental artery, suggesting omental hemorrhage. As he was hemodynamically stable, initial conservative management was chosen. However, a follow-up CT on day 7 demonstrated aneurysm enlargement, prompting laparoscopic partial omentectomy. Intraoperative findings included a 5-cm hematoma in the central omentum. Histopathological examination showed vacuolization of the tunica media and loss of the internal elastic lamina, confirming the diagnosis of SAM. The patient had an uneventful postoperative course and was discharged on the 3rd postoperative day.
CONCLUSIONS: This rare case of SAM-related omental bleeding was successfully treated with laparoscopic partial omentectomy. Tailored treatment strategies including laparoscopic surgery are essential for optimal outcomes in SAM.
en-copyright= kn-copyright= en-aut-name=MimataYudai en-aut-sei=Mimata en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=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=MinagiHitoshi en-aut-sei=Minagi en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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= en-keyword=segmental arterial mediolysis kn-keyword=segmental arterial mediolysis en-keyword=laparoscopic partial omentectomy kn-keyword=laparoscopic partial omentectomy en-keyword=hemoperitoneum kn-keyword=hemoperitoneum END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=6 article-no= start-page=1008 end-page=1016 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240422 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: Lynch syndrome (LS) is a dominantly inherited syndrome characterized by an increased risk for LS associated tumors such as colorectal cancer (CRC) and gastric cancer (GC). However, the clinical benefit of surveillance for GC remains unclear while it has already been recommended for CRC. This study aimed to elucidate the clinical features of GC in Japanese individuals with LS, and the risk of developing multiple GCs to build regional-tailored surveillance programs in LS patients with GC.
Methods: Data on Japanese individuals with LS were retrospectively collected from a single institution. The clinical features of GC, including the cumulative risk of multiple GCs, were analyzed.
Results: Among 96 individuals with LS (MLH1/MSH2/MSH6, 75:20:1), 32 GC lesions were detected in 15 individuals with LS (male/female, 11:4). The median age at initial GC diagnosis was 52.7?y (range: 28?71). Histological examination revealed a predominance of intestinal type (19/24: 87.5%). Moreover, the majority of the GC lesions (82%) were determined to have high-frequency of microsatellite instability. The cumulative risk of individuals with LS developing GC at 70?y was 31.3% (MLH1 36.1%, MSH2 18.0%). Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20?y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively.
Conclusion: Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC. en-copyright= kn-copyright= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=van SchaikThijs A. en-aut-sei=van Schaik en-aut-mei=Thijs A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AokiHideki en-aut-sei=Aoki en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoYumiko en-aut-sei=Sato en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuganoKokichi en-aut-sei=Sugano en-aut-mei=Kokichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkagiKiwamu en-aut-sei=Akagi en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshidaHideyuki en-aut-sei=Ishida en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakayaKohji en-aut-sei=Tanakaya en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School kn-affil= affil-num=3 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=4 en-affil=Department of Pathology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=5 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center 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 Genetic Medicine, Kyoundo Hospital, SSasaki Foundation kn-affil= affil-num=8 en-affil=Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center kn-affil= affil-num=9 en-affil=Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=10 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= en-keyword=cumulative risk kn-keyword=cumulative risk en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=Japanese individuals kn-keyword=Japanese individuals en-keyword=Lynch syndrome kn-keyword=Lynch syndrome en-keyword=multiple gastric cancers kn-keyword=multiple gastric cancers END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=5 article-no= start-page=271 end-page=277 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240329 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Japan MSA registry: A multicenter cohort study of multiple system atrophy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and various motor symptoms. While MSA-C (cerebellar type) predominates in East Asia, MSA-P (parkinsonian type) predominates in Europe and North America. This nationwide patient registry aimed to (1) conduct a prospective natural history study of MSA in Japan, (2) facilitate patient recruitment for clinical trials, and (3) deposit bioresources and clinical information in a biobank.
Methods: Thirteen institutions participated in this study. Clinical information was obtained by neurologists from the patients visiting the hospital every 12?months to assess the UMSARS Part 2 scores and by telephone interviews by nurses every 6?months to assess UMSARS Part 1 scores and to determine whether clinical events had occurred.
Results: Demographic data from 329 MSA patients (216 MSA-C and 113 MSA-P) were analyzed. The mean age at symptom onset was 58.2?years (standard deviation, 8.9); the mean duration of symptoms at enrollment was 3.5?years (standard deviation, 2.2). The mean 12-month changes in the UMSARS Part 1 and Part 2 scores were 7.9 (standard deviation, 5.6) and 6.4 (standard deviation, 5.9), respectively. The patient registry proved useful in recruiting participants for clinical trials, including those with gene variants. Clinical information and biospecimens were deposited in a biobank.
Discussion: The study highlighted the importance of telephone interviews in minimizing drop-out rates in natural history studies and demonstrated similar MSA progression rates across populations. The deposited bioresources are available to researchers upon request, aiming to contribute to future MSA researches. en-copyright= kn-copyright= en-aut-name=ChikadaAyaka en-aut-sei=Chikada en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MizusawaHidehiro en-aut-sei=Mizusawa en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakahashiYuji en-aut-sei=Takahashi en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatsunoMasahisa en-aut-sei=Katsuno en-aut-mei=Masahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaraKazuhiro en-aut-sei=Hara en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OnoderaOsamu en-aut-sei=Onodera en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IshiharaTomohiko en-aut-sei=Ishihara en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TadaMasayoshi en-aut-sei=Tada en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KuwabaraSatoshi en-aut-sei=Kuwabara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SugiyamaAtsuhiko en-aut-sei=Sugiyama en-aut-mei=Atsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamanakaYoshitaka en-aut-sei=Yamanaka en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakahashiRyosuke en-aut-sei=Takahashi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SawamotoNobukatsu en-aut-sei=Sawamoto en-aut-mei=Nobukatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SakatoYusuke en-aut-sei=Sakato en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IshimotoTomoyuki en-aut-sei=Ishimoto en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HanajimaRitsuko en-aut-sei=Hanajima en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=WatanabeYasuhiro en-aut-sei=Watanabe en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TakigawaHiroshi en-aut-sei=Takigawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=AdachiTadashi en-aut-sei=Adachi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TakashimaHiroshi en-aut-sei=Takashima en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=HigashiKeiko en-aut-sei=Higashi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KiraJunichi en-aut-sei=Kira en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=YabeIchiro en-aut-sei=Yabe en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=MatsushimaMasaaki en-aut-sei=Matsushima en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=OgataKatsuhisa en-aut-sei=Ogata en-aut-mei=Katsuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=IshikawaKinya en-aut-sei=Ishikawa en-aut-mei=Kinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=NishidaYoichiro en-aut-sei=Nishida en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=IshiguroTaro en-aut-sei=Ishiguro en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OzakiKokoro en-aut-sei=Ozaki en-aut-mei=Kokoro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NagataTetsuya en-aut-sei=Nagata en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Neurology, Nagoya University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=12 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=13 en-affil=Department of Neurology, Brain Research Institute, Niigata University kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=15 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=16 en-affil=Department of Neurology, Graduate School of Medicine, Chiba University kn-affil= affil-num=17 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Human Health Sciences, Kyoto University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Neurology, Kyoto University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=22 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=23 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=24 en-affil=Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University kn-affil= affil-num=25 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=26 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=27 en-affil=Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=28 en-affil=Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=29 en-affil=Department of Neurology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=30 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=31 en-affil=Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=32 en-affil=Department of Neurology, Higashi-Saitama National Hospital kn-affil= affil-num=33 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=34 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=35 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=36 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=37 en-affil=Department of Neurology and Neurological Science, Tokyo Medical and Dental University kn-affil= affil-num=38 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=multicenter cohort study kn-keyword=multicenter cohort study en-keyword=multiple system atrophy kn-keyword=multiple system atrophy en-keyword=natural history kn-keyword=natural history en-keyword=patient registry kn-keyword=patient registry END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=12 article-no= start-page=613 end-page=621 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association study of GBA1 variants with MSA based on comprehensive sequence analysis -Pitfalls in short-read sequence analysis depending on the human reference genome- en-subtitle= kn-subtitle= en-abstract= kn-abstract=Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by various combinations of autonomic failure, parkinsonism, and cerebellar ataxia. To elucidate variants associated with MSA, we have been conducting short-read-based whole-genome sequence analysis. In the process of the association studies, we initially focused on GBA1, a previously proposed susceptibility gene for MSA, to evaluate whether GBA1 variants can be efficiently identified despite its extraordinarily high homology with its pseudogene, GBA1LP. To accomplish this, we conducted a short-read whole-genome sequence analysis with alignment to GRCh38 as well as Sanger sequence analysis and compared the results. We identified five variants with inconsistencies between the two pipelines, of which three variants (p.L483P, p.A495P?p.V499V, p.L483_M489delinsW) were the results of misalignment due to minor alleles in GBA1P1 registered in GRCh38. The miscalling events in these variants were resolved by alignment to GRCh37 as the reference genome, where the major alleles are registered. In addition, a structural variant was not properly identified either by short-read or by Sanger sequence analyses. Having accomplished correct variant calling, we identified three variants pathogenic for Gaucher disease (p.S310G, p.L483P, and p.L483_M489delinsW). Of these variants, the allele frequency of p.L483P (0.003) in the MSA cases was higher than that (0.0011) in controls. The meta-analysis incorporating a previous report demonstrated a significant association of p.L483P with MSA with an odds ratio of 2.85 (95% CI; 1.05 ? 7.76, p = 0.0400). en-copyright= kn-copyright= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaMasaki en-aut-sei=Tanaka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NomotoJunko en-aut-sei=Nomoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=OmaeYosuke en-aut-sei=Omae en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaiYosuke en-aut-sei=Kawai en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TokunagaKatsushi en-aut-sei=Tokunaga en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NCBN Controls WGS Consortium en-aut-sei=NCBN Controls WGS Consortium en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=5 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=8 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=9 en-affil=Genome Medical Science Project, National Center for Global Health and Medicine kn-affil= affil-num=10 en-affil= kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=3 article-no= start-page=79 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of the expression of 5?FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S?1 adjuvant chemotherapy: Follow?up results of the Setouchi Lung Cancer Group Study 1201 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Managing elderly patients presents several challenges because of age?related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non?small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5?fluorouracil (5?FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5?FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S?1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5?FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross?complementation group 1 (ERCC1), were assessed via quantitative reverse?transcription PCR assays in 89 elderly patients (?75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S?1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that TS expression decreased significantly with aging, especially in the age group ?75. In the SCLG1201 trial, univariate analysis revealed that EGFR upregulation and TS downregulation were correlated with favorable recurrence?free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. EGFR mutations were associated with upregulation of DPD and EGFR, and downregulation of TS and ERCC1. In conclusion, although pathological stage is an independent prognostic factor for survival, EGFR upregulation and TS downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S?1 adjuvant chemotherapy. The age?related decrease in TS expression supports the potential benefit of 5?FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results. en-copyright= kn-copyright= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkumuraNorihito en-aut-sei=Okumura en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHiroyuki en-aut-sei=Suzuki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GembaKenicehi en-aut-sei=Gemba en-aut-mei=Kenicehi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SanoIsao en-aut-sei=Sano en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujinagaTakuji en-aut-sei=Fujinaga en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaMasafumi en-aut-sei=Kataoka en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerasakiYasuhiro en-aut-sei=Terasaki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KataokaKazuhiko en-aut-sei=Kataoka en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KosakaShinji en-aut-sei=Kosaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakamuraHiroshige en-aut-sei=Nakamura en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamashitaYoshinori en-aut-sei=Yamashita en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TakahashiYuta en-aut-sei=Takahashi en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=SatoHiroki en-aut-sei=Sato en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MoritaSatoshi en-aut-sei=Morita en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MatsuoKeitaro en-aut-sei=Matsuo en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=SakamotoJunichi en-aut-sei=Sakamoto en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Chest Surgery, Fukushima Medical University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima 720?0001, Japan; 8Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center kn-affil= affil-num=10 en-affil=Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Surgery, Saga Medical Center Koseikan kn-affil= affil-num=12 en-affil=Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=13 en-affil=Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=14 en-affil=Department of Thoracic Surgery, Shimane Prefectural Central Hospital kn-affil= affil-num=15 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=16 en-affil=Department of Thoracic Surgery, National Hospital Organization Yamaguchi?Ube Medical Center kn-affil= affil-num=17 en-affil=Department of Thoracic Surgery, Shimonoseki City Hospital kn-affil= affil-num=18 en-affil=Division of General Thoracic Surgery, Tottori University Hospital kn-affil= affil-num=19 en-affil=Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=20 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=23 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=24 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=26 en-affil=Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine kn-affil= affil-num=27 en-affil=Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute kn-affil= affil-num=28 en-affil=Tokai Central Hospital kn-affil= affil-num=29 en-affil=Department of Thoracic Surgery, Kyoto University Hospital kn-affil= affil-num=30 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=non?small cell lung cancer kn-keyword=non?small cell lung cancer en-keyword=elderly patients kn-keyword=elderly patients en-keyword=adjuvant chemotherapy kn-keyword=adjuvant chemotherapy en-keyword=S?1 kn-keyword=S?1 en-keyword=EGFR kn-keyword=EGFR en-keyword=TP kn-keyword=TP en-keyword=TS kn-keyword=TS en-keyword=OPRT kn-keyword=OPRT en-keyword=ERCC1 kn-keyword=ERCC1 en-keyword=DPD kn-keyword=DPD END start-ver=1.4 cd-journal=joma no-vol=120 cd-vols= no-issue=1 article-no= start-page=87 end-page=98 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=Comparable Clinical Outcomes Between Segmentectomy and Lobectomy for NSCLC With Unsuspected N1/N2: A Multicenter Real-World Data Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Segmentectomy for lung cancer has been increasingly performed. However, evidence regarding the necessity of additional surgical resection after the diagnosis of unsuspected N1 or N2 lymph node metastasis is limited.
Methods We conducted a multicenter, real-world data study of patients with any clinical T and N0 non-small cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between 2012 and 2021 and who subsequently received a diagnosis of pathologic N1 or N2 lymph node metastasis. Patients were categorized into lobectomy and segmentectomy groups. We analyzed overall survival (OS), recurrence-free survival (RFS), cumulative recurrence rates, and recurrence patterns using both unadjusted and propensity score?adjusted cohorts.
Results A total of 736 patients were in the lobectomy group, and 70 were in the segmentectomy group. In the unadjusted cohort, segmentectomy-treated patients were older, had a lower preoperative percentage of vital capacity, had smaller tumors, and received less postoperative adjuvant chemotherapy. The 5-year OS was significantly worse in the segmentectomy group (P = .011), with no significant differences in 5-year RFS or cumulative recurrence rates. In the propensity score?adjusted cohort, there were no significant differences in OS, RFS, or recurrence rates; however, the segmentectomy group had a higher rate of local recurrence.
Conclusions In patients with unsuspected N1 or N2 NSCLC, analysis using a cohort adjusted for patient background with propensity scores revealed no differences in OS, RFS, or cumulative recurrence rates between segmentectomy and lobectomy. This finding suggests that additional resection of the remaining segments may not be necessary for these patients. However, the higher rate of local recurrence in the segmentectomy group warrants careful consideration. en-copyright= kn-copyright= en-aut-name=RyukoTsuyoshi en-aut-sei=Ryuko en-aut-mei=Tsuyoshi 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=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=UenoTsuyoshi en-aut-sei=Ueno en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MisaoTakahiko en-aut-sei=Misao en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TorigoeHidejiro en-aut-sei=Torigoe en-aut-mei=Hidejiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WashioKazuhiro en-aut-sei=Washio en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TaoHiroyuki en-aut-sei=Tao en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkutaniDaisuke en-aut-sei=Okutani en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HayamaMakio en-aut-sei=Hayama en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UomotoMasashi en-aut-sei=Uomoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamadaEiji en-aut-sei=Yamada en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OtaniShinji en-aut-sei=Otani en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KurosakiTakeshi en-aut-sei=Kurosaki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YaginumaYuji en-aut-sei=Yaginuma en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NimanEito en-aut-sei=Niman en-aut-mei=Eito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KawamataOsamu en-aut-sei=Kawamata en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NishikawaHitoshi en-aut-sei=Nishikawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OtsukaTomoaki en-aut-sei=Otsuka en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshikawaTakeshi en-aut-sei=Yoshikawa en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=HayashiTatsuro en-aut-sei=Hayashi en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 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=27 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=Center for Innovative Clinical Medicine, Okayama University Hospital 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 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=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=7 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=8 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=21 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=22 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=23 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=24 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=25 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=26 en-affil=Okayama University Thoracic Surgery Study Group kn-affil= affil-num=27 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=10 article-no= start-page=1215 end-page=1227 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhanced design of pCMViR-TSC plasmid vector for sustainably high cargo gene expression in mammalian cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The first-generation pCMViR-TSC, implemented through the promoter sandwich rule, yields 10- to 100-fold higher gene expression than the standard plasmid used with the CMV (cytomegalovirus) or CAG promoter. However, the vectorfs shortcomings limit its utility to transient expression only, as it is not suitable for establishing stable transformants in mammalian cells. To overcome this weakness, we here introduce the improved plasmid vector pSAKA-4B, derived from pCMViR-TSC as a second-generation chromosome-insertable vector. This vector facilitates the linear entry of the expression unit into the TTAA site of DNA universally with transposase assistance. The vector is helpful for the indefinite expression of our target gene. The new vector system is proven here to be efficient in establishing stable transformants with a high likelihood of positive clones that exhibit significantly elevated expression levels of the delivered foreign gene. This system, alongside the first-generation vector, is therefore instrumental for diverse basic research endeavors concerning genes, proteins, cells, and animals, and potentially for clinical applications such as gene therapy. en-copyright= kn-copyright= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo 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=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaguchiYoshihiko en-aut-sei=Sakaguchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamauchiAkira en-aut-sei=Yamauchi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoKen-ichi en-aut-sei=Yamamoto en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakahashiTetta en-aut-sei=Takahashi en-aut-mei=Tetta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GoharaYuma en-aut-sei=Gohara en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OchiToshiki en-aut-sei=Ochi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=JiangFan en-aut-sei=Jiang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KomalasariNi Luh Gede Yoni en-aut-sei=Komalasari en-aut-mei=Ni Luh Gede Yoni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=RumaI Made Winarsa en-aut-sei=Ruma en-aut-mei=I Made Winarsa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SumardikaI Wayan en-aut-sei=Sumardika en-aut-mei=I Wayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ZhouJin en-aut-sei=Zhou en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HonjoTomoko en-aut-sei=Honjo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KuribayashiFutoshi en-aut-sei=Kuribayashi en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SagayamaKazumi en-aut-sei=Sagayama en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=InoueYusuke en-aut-sei=Inoue en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Microbiology, Tokushima Bunri University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=14 en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=15 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=16 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=17 en-affil=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology kn-affil= affil-num=18 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=19 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=20 en-affil=Organization for Research and Innovation Strategy, Okayama University kn-affil= affil-num=21 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University kn-affil= affil-num=23 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= en-keyword=Plasmid kn-keyword=Plasmid en-keyword=Gene engineering kn-keyword=Gene engineering en-keyword=Cancer kn-keyword=Cancer en-keyword=Cell culture kn-keyword=Cell culture 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=20250718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Advances in liquid biopsy for bone and soft-tissue sarcomas en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bone and soft-tissue sarcomas are a heterogeneous group of malignant tumors originating from mesenchymal tissues, accounting for approximately 1% of adult solid malignancies and 20% of pediatric solid malignancies. While blood-based tumor markers are available in major types of cancers, evidence demonstrating useful circulating biomarkers is limited in bone and soft-tissue sarcomas. Despite the development of combined modality treatments, a significant proportion of sarcoma patients respond poorly to chemotherapy or radiotherapy, leading to local relapse or distant metastasis. However, imaging methods, such as X-ray, computed tomography, positron emission tomography, magnetic resonance imaging, and scintigraphy, are mostly used to detect or monitor tumor development. Liquid biopsy is an emerging minimally invasive diagnostic technique that detects tumor-derived molecules in body fluids, including circulating tumor cells, circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), and circulating extracellular vesicles. This method offers new possibilities for early tumor detection, prognostic evaluation, and therapeutic monitoring and may serve as a benchmark for treatment modification. This review focuses on the current technological advances in liquid biopsy for bone and soft-tissue sarcoma and explores its potential role in guiding personalized treatments. If these modalities could determine resistance to ongoing therapy or the presence of minimal residual disease at the end of the treatment protocol, the obtained data would be important for determining whether to change treatment approaches or add adjuvant therapies. en-copyright= kn-copyright= en-aut-name=WangYilang en-aut-sei=Wang en-aut-mei=Yilang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= en-aut-name=IshimaruTakahiko en-aut-sei=Ishimaru en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoHiroya en-aut-sei=Kondo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 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= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Liquid biopsy kn-keyword=Liquid biopsy en-keyword=Bone sarcoma kn-keyword=Bone sarcoma en-keyword=Soft-tissue sarcoma kn-keyword=Soft-tissue sarcoma en-keyword=Circulating tumor cells kn-keyword=Circulating tumor cells en-keyword=Circulating nucleic acids kn-keyword=Circulating nucleic acids en-keyword=Circulating microvesicles kn-keyword=Circulating microvesicles END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=654 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biogeochemical impact of nickel and urea in the great oxidation event en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Great Oxidation Event marks the first substantial increase in atmospheric oxygen on Earth. Despite the oxygenic photosynthesis that emerged hundreds of million years before this event, the specific biogeochemical mechanisms responsible for maintaining low oxygen levels for an extended period remain elusive. Here, we show the critical role of urea as a nitrogen source for cyanobacteria, the cascading impact of nickel on abiotic urea production, and their combined effects on the proliferation of cyanobacteria leading to the great oxidation event. Urea formation was experimentally evaluated under simulated Archean conditions and cyanobacterial growth was monitored providing urea as the nitrogen source. Our findings demonstrate that urea can be produced in the Archean cyanobacterial habitats with UV-C irradiation, shedding light on the controversy regarding the evolution of nitrogen-fixing enzymes in primitive cyanobacteria. We propose that environmental conditions in the early Archean, characterized by elevated urea and nickel concentration, may have hindered cyanobacterial expansion, contributing to the delay between the evolution of oxygenic photosynthesis and the onset of the great oxidation event. en-copyright= kn-copyright= en-aut-name=RatnayakeDilan M. en-aut-sei=Ratnayake en-aut-mei=Dilan M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaRyoji en-aut-sei=Tanaka en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraEizo en-aut-sei=Nakamura en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=150 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in DNAJC7, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in DNAJC7 expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, DNAJC7 knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas DNAJC7 overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, dnajc7 knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in DNAJC7 to familial ALS with TDP-43 pathology. en-copyright= kn-copyright= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokotaOsamu en-aut-sei=Yokota en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=HaraguchiTakashi en-aut-sei=Haraguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawanoTomohito en-aut-sei=Kawano en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nakashima-YasudaHanae en-aut-sei=Nakashima-Yasuda en-aut-mei=Hanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko 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=HasegawaMasato en-aut-sei=Hasegawa en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HosonoYasuyuki en-aut-sei=Hosono en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TeradaSeishi en-aut-sei=Terada en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, National Hospital Organisation Minami-Okayama Medical Centre kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Psychiatry, Zikei Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science kn-affil= affil-num=14 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Amyotrophic lateral sclerosis kn-keyword=Amyotrophic lateral sclerosis en-keyword=Heat shock protein kn-keyword=Heat shock protein en-keyword=DNAJC7 kn-keyword=DNAJC7 en-keyword=TDP-43 kn-keyword=TDP-43 en-keyword=Live-cell imaging kn-keyword=Live-cell imaging en-keyword=Zebrafish disease model kn-keyword=Zebrafish disease model END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=27502 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Autoantibody spark response predicts treatment outcome in patients receiving chemoradiation followed by durvalumab therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=The PACIFIC regimen, comprising chemoradiotherapy (CRT) followed by maintenance with the immune checkpoint inhibitor (ICI) durvalumab, has become the standard of care for patients with unresectable non-small cell lung cancer (NSCLC). Although ICI is used to prevent recurrence by targeting residual microtumors, biomarkers capable of monitoring immune activity during this phase remain lacking. Here, we evaluated whether temporal changes in serum autoantibody levels can predict treatment efficacy. This retrospective study included 20 patients with unresectable stage II or III NSCLC who received the PACIFIC regimen. Serum autoantibodies against 130 antigens were quantified before CRT, after CRT, and two weeks after the first ICI dose. The primary outcome was progression-free survival (PFS), and its association with autoantibody dynamics was examined. We observed an immediate and strong autoantibody response (spark response [SR]) after ICI initiation in patients with favorable treatment outcomes. Patients with SR and programmed death ligand 1 (PD-L1) expression???50% showed better PFS (two-year PFS; 72.9% vs. 18.2%, p?=?0.0021). These findings suggest that serial monitoring of serum autoantibodies can provide a noninvasive approach to assess immune activity and predict treatment outcomes in patients receiving CRT or ICI therapy. en-copyright= kn-copyright= en-aut-name=MoriTakeru en-aut-sei=Mori en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitagawaMio en-aut-sei=Kitagawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaTomokazu en-aut-sei=Hasegawa en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SomeyaMasanori en-aut-sei=Someya en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuchiyaTakaaki en-aut-sei=Tsuchiya en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GochoToshio en-aut-sei=Gocho en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HonjoTomoko en-aut-sei=Honjo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DateMirei en-aut-sei=Date en-aut-mei=Mirei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriiMariko en-aut-sei=Morii en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiology, Sapporo Medical University School of Medicine kn-affil= affil-num=3 en-affil=Department of Radiology, Sapporo Medical University School of Medicine kn-affil= affil-num=4 en-affil=Department of Radiology, Sapporo Medical University School of Medicine kn-affil= affil-num=5 en-affil=Department of Radiology, Sapporo Medical University School of Medicine kn-affil= affil-num=6 en-affil=Department of Radiology, Sapporo Medical University School of Medicine kn-affil= affil-num=7 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, 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 Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Autoantibodies kn-keyword=Autoantibodies en-keyword=PACIFIC regimen kn-keyword=PACIFIC regimen en-keyword=ICIs kn-keyword=ICIs en-keyword=Immune monitoring kn-keyword=Immune monitoring END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=6 article-no= start-page=e00110-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mycobacterium tuberculosis bacillus induces pyroptosis in human lung fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported that live, but not dead, virulent Mycobacterium tuberculosis (Mtb) H37Rv bacilli induce cell death in human lung fibroblast cell lines, MRC-5, MRC-9, and TIG-1. Here, using two distinct Mtb strains from two different lineages (HN878 lineage 2 and H37Rv lineage 4), we confirmed cell death at day 2 after infection with a device that measures cell growth/cytotoxicity in real time (Maestro-Z [AXION]). Mtb bacilli uptake by the fibroblast was confirmed with a transmission electron microscope on day 2. Expressions of inflammatory cytokines and interleukin (IL)?1ƒÀ, IL-6, and IL-8 were observed when exposed to live, but not dead bacteria. The cell death of fibroblasts induced by both Mtb strains tested was prevented by caspase-1/4 and NLRP3 inflammasome inhibitors, but not by caspase-3 and caspase-9 inhibitors. Therefore, we classified the fibroblast cell death by Mtb infection as pyroptosis. To investigate the biological and pathological relevance of fibroblast cell death by Mtb infection, we performed dual RNA-Seq analysis on Mtb within fibroblasts and Mtb-infected fibroblasts at day 2. In Mtb bacilli tcrR, secE2, ahpD, and mazF8 genes were highly induced during infection. These genes play roles in survival in a hypoxic environment, production of a calcium-binding protein-inducing cytokine, and regulation of transcription in a toxin-antitoxin system. The gene expressions of IL-1ƒÀ, IL-6, and IL-8, caspase-4, and NLRP3, but not of caspase-3 and caspase-9, were augmented in Mtb bacilli-infected fibroblasts. Taken together, our study suggests that Mtb bacilli attempt to survive in lung fibroblasts and that pyroptosis of the host fibroblasts activates the immune system against the infection. en-copyright= kn-copyright= en-aut-name=TakiiTakemasa en-aut-sei=Takii en-aut-mei=Takemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaHiroyuki en-aut-sei=Yamada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotozonoChihiro en-aut-sei=Motozono en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiSho en-aut-sei=Yamasaki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TorrellesJordi B. en-aut-sei=Torrelles en-aut-mei=Jordi B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TurnerJoanne en-aut-sei=Turner en-aut-mei=Joanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimishimaAoi en-aut-sei=Kimishima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsamiYukihiro en-aut-sei=Asami en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HidaShigeaki en-aut-sei=Hida en-aut-mei=Shigeaki 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=OnozakiKikuo en-aut-sei=Onozaki en-aut-mei=Kikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=2 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=3 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=4 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=5 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I?CARE) kn-affil= affil-num=6 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I?CARE) kn-affil= affil-num=7 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=8 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=9 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=11 en-affil=Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=12 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= en-keyword=Mycobacterium tuberculosis kn-keyword=Mycobacterium tuberculosis en-keyword=pyroptosis kn-keyword=pyroptosis en-keyword=caspase kn-keyword=caspase en-keyword=RNA-Seq kn-keyword=RNA-Seq en-keyword=cytokine kn-keyword=cytokine en-keyword=fibroblasts kn-keyword=fibroblasts END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=11 article-no= start-page=348 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Coronal Cementum and Reduced Enamel Epithelium on Occlusal Surface of Impacted Wisdom Tooth in a Human en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: There is only limited research on the coronal cementum of a tooth, and the mechanisms of its forming process are not well-defined. This report presents a coronal cementum on the occlusal surfaces of enamel in an impacted wisdom tooth in a human, which is not nearly the cervical portion. Materials and Methods: The tooth (Tooth #1) was derived from a 46-year-old female. Histological analysis, including hematoxylin and eosin (HE) and toluidine blue (TB) staining, and Scanning Electron Microscopy and Energy Dispersive X-ray Spectrometer (SEM-EDS) analysis of the extracted tooth were conducted. Radiographic examination showed that Tooth #1 was horizontally impacted in the maxilla and had the apex of a single root placed between the buccal and palatal roots of Tooth #2. Results: Coronal cementum was distributed widely on the enamel, and reduced enamel epithelium was also found with enamel matrix proteins histologically. The formation of acellular cementum was observed to be more predominant than that of the cellular cementum in Tooth #1. SEM showed that the occlusal cementum connected directly with enamel. Calcium mapping revealed an almost similar occlusal cementum and enamel. In addition, the spectrum of elements in coronal cementum resembled the primary cementum according to SEM-EDS. Discussion: Thus, coronal cementogenesis in impacted human teeth might be related to the existence of reduced enamel epithelium. en-copyright= kn-copyright= en-aut-name=HorieNaohiro en-aut-sei=Horie en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurataMasaru en-aut-sei=Murata en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MinamidaYasuhito en-aut-sei=Minamida en-aut-mei=Yasuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagayasuHiroki en-aut-sei=Nagayasu en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimoTsuyoshi en-aut-sei=Shimo en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkazawaToshiyuki en-aut-sei=Akazawa en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujigiwaHidetsugu en-aut-sei=Tsujigiwa en-aut-mei=Hidetsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaikelYoussef en-aut-sei=Haikel en-aut-mei=Youssef kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=2 en-affil=Division of Regenerative Medicine, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=3 en-affil=Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=4 en-affil=Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=5 en-affil=Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido kn-affil= affil-num=6 en-affil=Industrial Technology and Environment Research Development, Hokkaido Research Organization kn-affil= affil-num=7 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=8 en-affil=Department of Biomaterials and Bioengineering, Institut National de la Sant? et de la Recherche m?dicale Unit? Mixte de Recherche (INSERM UMR) _S 1121, University of Strasbourg kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=coronal cementum kn-keyword=coronal cementum en-keyword=human kn-keyword=human en-keyword=reduced epithelium kn-keyword=reduced epithelium en-keyword=impacted tooth kn-keyword=impacted tooth END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=hcaf176 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Disseminated Mycobacterium chelonae infection predominantly involving the facial region of an immunocompromised elderly patient en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SazumiYosuke en-aut-sei=Sazumi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MuenrayaPoowadon en-aut-sei=Muenraya en-aut-mei=Poowadon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiharaSatoru en-aut-sei=Sugihara en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawakamiYoshio en-aut-sei=Kawakami en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=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 Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=779 cd-vols= no-issue= article-no= start-page=152453 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=1,2-naphthoquinone enhances IFN-ƒÁ-induced MHC-I expression in dendritic cells, thereby inducing CD8 T cell activation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells play a crucial role in immune responses by capturing pathogens and presenting antigens to T cells via major histocompatibility complex (MHC) molecules, thus triggering adaptive immune responses. 1,2-naphthoquinone (1,2-NQ), a quinone found in diesel exhaust and cigarette smoke, has various physiological functions. In this study, we investigated the effect of 1,2-NQ on the expression of antigen presentation-related molecules in the dendritic cell line DC2.4. The results revealed that 1,2-NQ enhanced the IFN-ƒÁ-induced upregulation of MHC-I expression at the transcriptional level. Moreover, it upregulated the expression of NLRC5, a transcriptional activator of MHC-I. 1,2-NQ is a reactive oxygen species (ROS) producing reagent. The 1,2-NQ-induced upregulation of MHC-I expression and downregulation of MHC-II expression were abolished by the ROS scavenger N-acetylcysteine. Similar effects on MHC expression were also observed with ROS-inducing reagents, such as paraquat and diethyl maleate. In addition, dendritic cells stimulated with 1,2-NQ exhibited enhanced efficacy in CD8 T cell activation, which was accompanied by increased IFN-ƒÁ production by T cells. These findings demonstrate that 1,2-NQ enhances the IFN-ƒÁ-induced activation of dendritic cells and promotes the activation of CD8 T cells. en-copyright= kn-copyright= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazatoKanon en-aut-sei=Miyazato en-aut-mei=Kanon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobataKai en-aut-sei=Kobata en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=1,2-Napthoquinone kn-keyword=1,2-Napthoquinone en-keyword=Dendritic cell kn-keyword=Dendritic cell en-keyword=IFN-ƒÁ kn-keyword=IFN-ƒÁ en-keyword=MHC-I kn-keyword=MHC-I en-keyword=CD8 T cell kn-keyword=CD8 T cell END start-ver=1.4 cd-journal=joma no-vol=122 cd-vols= no-issue=32 article-no= start-page=e2501933122 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250805 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural insights into a citrate transporter that mediates aluminum tolerance in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=HvAACT1 is a major aluminum (Al)-tolerance gene in barley, encoding a citrate transporter that belongs to the multidrug and toxic compound extrusion (MATE) family. This transporter facilitates citrate secretion from the roots, thereby detoxifying external Al ions?a major constraint of crop production on acidic soils. In this study, we present the outward-facing crystal structure of HvAACT1, providing insights into a citrate transport mechanism. The putative citrate binding site consists of three basic residues?K126 in transmembrane helix 2 (TM2), R358 in TM7, and R535 in TM12?creating substantial positive charges in the C-lobe cavity. Proton coupling for substrate transport may involve two pairs of aspartate residues in the N-lobe cavity, one of which corresponds to the essential Asp pair found in prokaryotic H+-coupled MATE transporters belonging to the DinF subfamily. Structural coupling between proton uptake in the N-lobe and citrate extrusion in the C-lobe can be enabled by an extensive, unique hydrogen-bonding network at the extracellular half of the N-lobe. Mutation-based functional analysis, structural comparisons, molecular dynamics simulation, and phylogenic analysis suggest an evolutionary link between citrate MATE transporters and the DinF MATE subfamily. Our findings provide a solid structural basis for citrate transport by HvAACT1 in barley and contribute to a broader understanding of citrate transporter structures in other plant species. en-copyright= kn-copyright= en-aut-name=Nguyen ThaoTran en-aut-sei=Nguyen Thao en-aut-mei=Tran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Mitani-UenoNamiki en-aut-sei=Mitani-Ueno en-aut-mei=Namiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UranoRyo en-aut-sei=Urano en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitohYasunori en-aut-sei=Saitoh en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangPeitong en-aut-sei=Wang en-aut-mei=Peitong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=ShinodaWataru en-aut-sei=Shinoda en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Division of Superconducting and Functional Materials, Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=5 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=8 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=9 en-affil=Research Core for Plant Stress Science, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=10 en-affil=Degree Program in Interdisciplinary Sciences, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= en-keyword=barley kn-keyword=barley en-keyword=aluminum resistance kn-keyword=aluminum resistance en-keyword=membrane protein structure kn-keyword=membrane protein structure en-keyword=citrate transporter kn-keyword=citrate transporter en-keyword=MATE transporter kn-keyword=MATE transporter END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=8 article-no= start-page=3474 end-page=3475 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250806 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gene replacement therapy for centronuclear myopathy: A breakthrough in complex genetic muscle disease en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakedaTetsuya en-aut-sei=Takeda en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=90 cd-vols= no-issue=1 article-no= start-page=29 end-page=36 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=Elucidation of the phylogenetic relationships among <i>Alpinia</i> species native to the Nansei Islands, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Alpinia species (A. intermedia, A. zerumbet, A. formosana, A. uraiensis, and unidentified strains native to the Daito Islands), which are native to the Nansei Islands, Japan are ornamental plants that can be used as resources to produce seasonings and antibacterial and antiviral substances. Despite the usefulness of these plants, little scientific research has been conducted on their phylogenetic relationships. In this study, their phylogenetic relationships were examined based on genomic and chloroplast DNA polymorphisms, repetitive sequence abundance, and cytogenetic perspectives. The results indicated that A. formosana is most likely the outcome of a hybrid of A. zerumbet and A. intermedia, and the unidentified strains native to the Daito Islands are the outcomes of a hybrid of A. zerumbet and A. uraiensis. Immunostaining with a newly produced anti-centromere-specific histone H3 (CENH3) antibody revealed that the number of chromosomes in these species was 2n=48. en-copyright= kn-copyright= en-aut-name=NagakiKiyotaka en-aut-sei=Nagaki en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NarusakaMari en-aut-sei=Narusaka en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NarusakaYoshihiro en-aut-sei=Narusaka en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Okayama Prefectural Technology Center for Agriculture, Forestry, and Fisheries, Research Institute for Biological Sciences (RIBS) kn-affil= affil-num=3 en-affil=Okayama Prefectural Technology Center for Agriculture, Forestry, and Fisheries, Research Institute for Biological Sciences (RIBS) kn-affil= en-keyword=Alpinia kn-keyword=Alpinia en-keyword=Nansei Islands kn-keyword=Nansei Islands en-keyword=Chromosome number kn-keyword=Chromosome number en-keyword=CENH3 (centromere-specific histone H3) kn-keyword=CENH3 (centromere-specific histone H3) END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=12 article-no= start-page=e202402802 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Chromosome-specific barcode system with centromeric repeat in cultivated soybean and wild progenitor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Wild soybean Glycine soja is the progenitor of cultivated soybean Glycine max. Information on soybean functional centromeres is limited despite extensive genome analysis. These species are an ideal model for studying centromere dynamics for domestication and breeding. We performed a detailed chromatin immunoprecipitation analysis using centromere-specific histone H3 protein to delineate two distinct centromeric DNA sequences with unusual repeating units with monomer sizes of 90?92 bp (CentGm-1) and 413-bp (CentGm-4) shorter and longer than standard nucleosomes. These two unrelated DNA sequences with no sequence similarity are part of functional centromeres in both species. Our results provide a comparison of centromere properties between a cultivated and a wild species under the effect of the same kinetochore protein. Possible sequence homogenization specific to each chromosome could highlight the mechanism for evolutionary conservation of centromeric properties independent of domestication and breeding. Moreover, a unique barcode system to track each chromosome is developed using CentGm-4 units. Our results with a unifying centromere composition model using CentGm-1 and CentGm-4 superfamilies could have far-reaching implications for comparative and evolutionary genome research. en-copyright= kn-copyright= en-aut-name=TekAhmet L en-aut-sei=Tek en-aut-mei=Ahmet L kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagakiKiyotaka en-aut-sei=Nagaki en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Y?ld?z Akkam??H?meyra en-aut-sei=Y?ld?z Akkam?? en-aut-mei=H?meyra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaKeisuke en-aut-sei=Tanaka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHisato en-aut-sei=Kobayashi en-aut-mei=Hisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Agricultural Genetic Engineering, Ayhan ?ahenk Faculty of Agricultural Sciences and Technologies, Ni?de ?mer Halisdemir University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Department of Agricultural Genetic Engineering, Ayhan ?ahenk Faculty of Agricultural Sciences and Technologies, Ni?de ?mer Halisdemir University kn-affil= affil-num=4 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= affil-num=5 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=8 article-no= start-page=522 end-page=532 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis and biochemical characterization of naphthoquinone derivatives targeting bacterial histidine kinases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Waldiomycin is an inhibitor of histidine kinases (HKs). Although most HK inhibitors target the ATP-binding region, waldiomycin binds to the intracellular dimerization domain (DHp domain) with its naphthoquinone moiety presumed to interact with the conserved H-box region. To further develop inhibitors targeting the H-box, various 2-aminonaphthoquinones with cyclic, aliphatic, or aromatic amino groups and naphtho [2,3-d] isoxazole-4,9-diones were synthesized. These compounds were tested for their inhibitory activity (IC50) against WalK, an essential HK for Bacillus subtilis growth, and their minimum inhibitory concentrations (MIC) against B. subtilis. As a result, 11 novel HK inhibitors were obtained as naphthoquinone derivatives (IC50: 12.6?305??M, MIC: 0.5?128??g?ml?1). The effect of representative compounds on the expression of WalK/WalR regulated genes in B. subtilis was investigated. Four naphthoquinone derivatives induced the expression of iseA (formerly yoeB), whose expression is negatively regulated by the WalK/WalR system. This suggests that these compounds inhibit WalK in B. subtilis cells, resulting in antibacterial activity. Affinity selection/mass spectrometry analysis was performed to identify whether these naphthoquinone derivatives interact with WalK in a manner similar to waldiomycin. Three compounds were found to competitively inhibit the binding of waldiomycin to WalK, suggesting that they bind to the H-box region conserved in HKs and inhibit HK activity. en-copyright= kn-copyright= en-aut-name=IshikawaTeruhiko en-aut-sei=Ishikawa en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EguchiYoko en-aut-sei=Eguchi en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IgarashiMasayuki en-aut-sei=Igarashi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkajimaToshihide en-aut-sei=Okajima en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitaKohei en-aut-sei=Mita en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamasakiYuri en-aut-sei=Yamasaki en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SumikuraKaho en-aut-sei=Sumikura en-aut-mei=Kaho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkumuraTaisei en-aut-sei=Okumura en-aut-mei=Taisei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TabuchiYuna en-aut-sei=Tabuchi en-aut-mei=Yuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HayashiChigusa en-aut-sei=Hayashi en-aut-mei=Chigusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=PasquaMartina en-aut-sei=Pasqua en-aut-mei=Martina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ColucciaMarco en-aut-sei=Coluccia en-aut-mei=Marco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ProssedaGianni en-aut-sei=Prosseda en-aut-mei=Gianni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ColonnaBianca en-aut-sei=Colonna en-aut-mei=Bianca kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KohayakawaChie en-aut-sei=Kohayakawa en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TaniAkiyoshi en-aut-sei=Tani en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HarutaJun-ichi en-aut-sei=Haruta en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UtsumiRyutaro en-aut-sei=Utsumi en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=2 en-affil=Department of Science and Technology on Food Safety, Faculty of Biology-Oriented Science and Technology, Kindai University kn-affil= affil-num=3 en-affil=Institute of Microbial Chemistry (BIKAKEN) kn-affil= affil-num=4 en-affil=SANKEN (The Institute of Scientific and Industrial Research), Osaka University kn-affil= affil-num=5 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=10 en-affil=Institute of Microbial Chemistry (BIKAKEN) kn-affil= affil-num=11 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, gC. Darwinh, Sapienza University of Rome kn-affil= affil-num=12 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, gC. Darwinh, Sapienza University of Rome kn-affil= affil-num=13 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, gC. Darwinh, Sapienza University of Rome kn-affil= affil-num=14 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, gC. Darwinh, Sapienza University of Rome kn-affil= affil-num=15 en-affil=Department of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=16 en-affil=Compound Library Screening Center, Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=17 en-affil=Department of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=18 en-affil=SANKEN (The Institute of Scientific and Industrial Research), Osaka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=11 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250707 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dual roles of suberin deposition at the endodermal Casparian strip in manganese uptake of rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice roots are characterized by having two Casparian strips (CSs) at the exodermis and endodermis, where transporters for mineral nutrients are expressed. However, the exact role of the CS in expression of the transporters and subsequent nutrient uptake is poorly understood. Here, we first investigated the role of the CS in manganese (Mn) uptake by using a rice mutant (oscasp1) defective in formation of the endodermal CS. Knockout of OsCASP1 resulted in decreased Mn uptake under limited Mn conditions, but increased Mn uptake at high Mn concentration. Immunostaining revealed that knockout of OsCASP1 did not affect the cell specificity of localization of two transporters (OsNramp5 and OsMTP9) required for Mn uptake, but decreased the protein abundance of these transporters at the endodermis regardless of Mn concentrations tested. Furthermore, we found that overaccumulation of suberin at the endodermis of the mutants suppressed the expression of two transporters; the expression of the two transporters was only observed in the endodermal cells without suberin deposition, but not in the cells with suberin deposition. Taken together, our results indicate that there are two roles for the CS in Mn uptake; maintaining normal expression of the transporters at limited Mn concentration and preventing Mn diffusion to the stele at high Mn concentration. en-copyright= kn-copyright= en-aut-name=FujiiToshiki en-aut-sei=Fujii en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Casparian strip kn-keyword=Casparian strip en-keyword=endodermis kn-keyword=endodermis en-keyword=manganese transporter kn-keyword=manganese transporter en-keyword=rice kn-keyword=rice en-keyword=root kn-keyword=root en-keyword=suberin deposition kn-keyword=suberin deposition END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=3 article-no= start-page=99 end-page=117 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Generation and characterization of cerebellar granule neurons specific knockout mice of Golli-MBP en-subtitle= kn-subtitle= en-abstract= kn-abstract=Golli?myelin basic proteins, encoded by the myelin basic protein gene, are widely expressed in neurons and oligodendrocytes in the central nervous system. Further, prior research has shown that Golli?myelin basic protein is necessary for myelination and neuronal maturation during central nervous system development. In this study, we established Golli?myelin basic protein-floxed mice to elucidate the cell-type-specific effects of Golli?myelin basic protein knockout through the generation of conditional knockout mice (Golli?myelin basic proteinsfl/fl; E3CreN), in which Golli?myelin basic proteins were specifically deleted in cerebellar granule neurons, where Golli?myelin basic proteins are expressed abundantly in wild-type mice. To investigate the role of Golli?myelin basic proteins in cerebellar granule neurons, we further performed histopathological analyses of these mice, with results indicating no morphological changes or degeneration of the major cellular components of the cerebellum. Furthermore, behavioral analysis showed that Golli?myelin basic proteinsfl/fl; E3CreN mice were healthy and did not display any abnormal behavior. These results suggest that the loss of Golli?myelin basic proteins in cerebellar granule neurons does not lead to cerebellar perturbations or behavioral abnormalities. This mouse model could therefore be employed to analyze the effect of Golli?myelin basic protein deletion in specific cell types of the central nervous system, such as other neuronal cells and oligodendrocytes, or in lymphocytes of the immune system. en-copyright= kn-copyright= en-aut-name=MiyazakiHaruko en-aut-sei=Miyazaki en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiokaSaki en-aut-sei=Nishioka en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamanakaTomoyuki en-aut-sei=Yamanaka en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeManabu en-aut-sei=Abe en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImamuraYukio en-aut-sei=Imamura en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyasakaTomohiro en-aut-sei=Miyasaka en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KakudaNobuto en-aut-sei=Kakuda en-aut-mei=Nobuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimogoriTomomi en-aut-sei=Shimogori en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamakawaKazuhiro en-aut-sei=Yamakawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IkawaMasahito en-aut-sei=Ikawa en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NukinaNobuyuki en-aut-sei=Nukina en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University kn-affil= affil-num=3 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= affil-num=4 en-affil=Department of Animal Model Development, Brain Research Institute, Niigata University kn-affil= affil-num=5 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= affil-num=6 en-affil=Faculty of Life and Medical Sciences, Doshisha University kn-affil= affil-num=7 en-affil=Faculty of Life and Medical Sciences, Doshisha University kn-affil= affil-num=8 en-affil=Department of Molecular Biology and Biochemistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Laboratory for Molecular Mechanisms of Brain Development, RIKEN Center for Brain Science kn-affil= affil-num=10 en-affil=Laboratory for Neurogenetics, RIKEN Center for Brain Science kn-affil= affil-num=11 en-affil=Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University kn-affil= affil-num=12 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= en-keyword=Golli-MBP kn-keyword=Golli-MBP en-keyword=Cerebellar granule neuron kn-keyword=Cerebellar granule neuron en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=Conditional knockout kn-keyword=Conditional knockout END start-ver=1.4 cd-journal=joma no-vol=218 cd-vols= no-issue= article-no= start-page=104922 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alteration of perineuronal nets and parvalbumin interneurons in prefrontal cortex and hippocampus, and correlation with blood corticosterone in activity-based anorexia model mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anorexia nervosa (AN) is an eating disorder characterized by restricted energy intake, severely underweight status, and frequent hyperactivity. Previous research has shown structural and functional alterations in the medial prefrontal cortex (mPFC) and hippocampus of AN patients. To investigate the pathological mechanism of AN, we analyzed the expression and distribution of parvalbumin (PV) interneurons and perineuronal nets (PNNs), which are implicated in the pathology of neuropsychiatric disorders, in the mPFC and hippocampus dorsal (HPCd) and ventral (HPCv) using an activity-based anorexia (ABA) mouse model. We found that PNN expression and density increased in the mPFC, with minor alterations in the HPCd and HPCv of ABA mice. The expression and distribution of PV neurons were unchanged in the brains of ABA mice, except for a regional decrease in PV-expressing neuron density in the HPCd. Co-localization analysis showed an increased number of PNNs enwrapping PV-negative neurons in the mPFC of ABA mice. Furthermore, the upregulation of PNN expression in the mPFC was positively correlated with elevated blood corticosterone levels, a well-known stress indicator, in ABA mice. Our findings suggest that the increased expression and distribution of PNNs surrounding PV-negative neurons in the mPFC may indicate the pathological mechanisms of AN. en-copyright= kn-copyright= en-aut-name=NguyenHoang Duy en-aut-sei=Nguyen en-aut-mei=Hoang Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiHaruko en-aut-sei=Miyazaki en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaiHiroki en-aut-sei=Kawai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anorexia nervosa kn-keyword=anorexia nervosa en-keyword=activity-based anorexia kn-keyword=activity-based anorexia en-keyword=perineuronal nets kn-keyword=perineuronal nets en-keyword=parvalbumin kn-keyword=parvalbumin en-keyword=corticosterone kn-keyword=corticosterone en-keyword=prefrontal cortex kn-keyword=prefrontal cortex en-keyword=hippocampus kn-keyword=hippocampus 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=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electrostatically]Driven Collapse of Polyelectrolytes: The?Role of the Solvent's Dielectric Constant en-subtitle= kn-subtitle= en-abstract= kn-abstract=We experimentally confirm a longstanding theoretical prediction of counterion-induced polyelectrolyte collapse in low dielectric media. The scattering behavior of polystyrene sulfonate in different solvents with dielectric permittivities in the range of ƒÃ ? 12 ? 180 is investigated. For high and intermediate ƒÃ media, typical polyelectrolyte behavior is observed: the correlation length (ƒÌ) scales with concentration (c) as ƒÌ ? c?1?2, as predicted by various theories. When the dielectric constant of the solvent decreases below ? 22, a scaling of ƒÌ ? c?1?3, characteristic of partially collapsed polyelectrolytes, is observed. For these solvents, the correlation peak disappears at high concentrations. Interestingly, polyelectrolyte collapse is observed under both solvophilic and solvophobic conditions, supporting the existence of attractive electrostatic interactions. These results are in qualitative agreement with theoretical predictions which expect chain collapse in low dielectric media due to the influence of condensed counterions, either via dipolar attraction and/or charge-correlation-induced attractions. en-copyright= kn-copyright= en-aut-name=GulatiAnish en-aut-sei=Gulati en-aut-mei=Anish kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MengLingzi en-aut-sei=Meng en-aut-mei=Lingzi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeTakaichi en-aut-sei=Watanabe en-aut-mei=Takaichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LopezCarlos G. en-aut-sei=Lopez en-aut-mei=Carlos G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Institute of Physical Chemistry, RWTH Aachen University kn-affil= affil-num=2 en-affil=Materials Science and Engineering Department, The Pennsylvania State University, State College kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University kn-affil= affil-num=4 en-affil=Materials Science and Engineering Department, The Pennsylvania State University, State College kn-affil= en-keyword=counterion kn-keyword=counterion en-keyword=dipole kn-keyword=dipole en-keyword=polyelectrolyte kn-keyword=polyelectrolyte en-keyword=SANS kn-keyword=SANS en-keyword=SAXS kn-keyword=SAXS en-keyword=scattering kn-keyword=scattering END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=e70146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Gastric Atypical Lipomatous Tumor/Well]Differentiated Liposarcoma With Endoscopic Morphological Changes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Atypical lipomatous tumor/well-differentiated liposarcoma is a locally aggressive mesenchymal neoplasm composed of adipocytes and stromal cells. Gastric cases are exceedingly rare, and their malignant potential remains unclear. We report a case of a woman in her 60s who was found to have multiple submucosal tumor-like lesions of the stomach. Over time, the tumors increased in size, requiring a laparoscopic partial gastrectomy. Histological examination revealed a tumor composed of both fatty tissue and fibrous stroma with nuclear atypia. Immunohistochemistry showed positivity for CDK4 and MDM2, and fluorescence in situ hybridization confirmed MDM2 amplification, leading to a diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma. This case presented an unusual gastric manifestation, with multiple submucosal tumor-like lesions on endoscopy and exhibiting progressive morphological changes over several years. en-copyright= kn-copyright= en-aut-name=OmoteRika en-aut-sei=Omote en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmoteShizuma en-aut-sei=Omote en-aut-mei=Shizuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SonobeHiroshi en-aut-sei=Sonobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamanoRyosuke en-aut-sei=Hamano en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaShinya en-aut-sei=Otsuka en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InagakiMasaru en-aut-sei=Inagaki en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Fukuyama Minami Hospital kn-affil= affil-num=3 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Gastroenterology, NHO Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=atypical lipomatous tumor kn-keyword=atypical lipomatous tumor en-keyword=CDK4 kn-keyword=CDK4 en-keyword=MDM2 kn-keyword=MDM2 en-keyword=stomach kn-keyword=stomach en-keyword=well-differentiated liposarcoma kn-keyword=well-differentiated liposarcoma END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue= article-no= start-page=104719 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Near-infrared photoimmunotherapy for recurrent cancer at the base of the tongue en-subtitle= kn-subtitle= en-abstract= kn-abstract=Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapeutic approach that targets epidermal growth factor receptor (EGFR). In NIR-PIT, administration of cetuximab sarotalocan sodium is followed by laser irradiation of the affected area, which theoretically should induce tumor cell death. However, residual tumors are occasionally observed. This study investigated factors that influence the therapeutic efficacy of NIR-PIT in cases of recurrence of cancer at the base of the tongue. Six patients undergoing 11 treatment cycles were analyzed, focusing on the puncture interval of cylindrical diffusers and the expression of EGFR in tumors. The results demonstrated that a puncture interval of ?12 mm significantly enhanced therapeutic efficacy, with one case achieving complete response. EGFR expression was positive in all cases and expression score showed no significant change between before and after treatment. These findings suggest that puncture interval plays a critical role in therapeutic outcomes, whereas EGFR expression may not directly influence treatment efficacy. en-copyright= kn-copyright= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoJunya en-aut-sei=Matsumoto en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimotoShohei en-aut-sei=Fujimoto en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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 Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Hematopathology, Okayama University Graduate School of Health 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= affil-num=5 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=ear-infrared photoimmunotherapy (NIR-PIT) kn-keyword=ear-infrared photoimmunotherapy (NIR-PIT) en-keyword=Epidermal growth factor receptor (EGFR) kn-keyword=Epidermal growth factor receptor (EGFR) en-keyword=Cylindrical diffuser kn-keyword=Cylindrical diffuser en-keyword=Puncture interval kn-keyword=Puncture interval en-keyword=Base of tongue cancer kn-keyword=Base of tongue cancer END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=26752 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250723 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ADAR1 as a prognostic marker for patients with colorectal cancer and synchronous liver metastasis and a predictor of chemotherapy efficacy en-subtitle= kn-subtitle= en-abstract= kn-abstract=RNA editing by adenosine deaminase acting on RNA (ADAR) enzymes plays a role in cancer progression. However, its clinical significance in metastatic colorectal cancer (CRC) remains unclear. This study aimed to evaluate whether ADAR1 expression predicts prognosis and treatment response in colorectal cancer (CRC) with synchronous liver metastasis. This study included 40 patients with stage IV CRC and synchronous liver metastases. ADAR1 expression in tumor tissues was evaluated using immunohistochemistry. Expression levels were quantified using the immunoreactive score, and associations with clinicopathological features, overall survival (OS), and chemotherapy response were examined. High ADAR1 expression was significantly associated with multiple liver metastases (P?=?0.0206), lymph node metastasis (P = 0.0241), and reduced response to chemotherapy (P?=?0.0224). Significantly shorter OS was observed in patients with high ADAR1 expression in the nucleus (P?=?0.0458). ADAR1 expression was an independent prognostic factor comparable to the presence of extrahepatic metastases. Low ADAR1 expression was correlated with a higher likelihood of achieving a response to chemotherapy. ADAR1 expression can reflect tumor aggressiveness and chemotherapy resistance in patients with CRC and synchronous liver metastasis. ADAR1 has considerable potential as a dual-purpose biomarker for stratifying patients based on prognosis and optimizing treatment intensity. en-copyright= kn-copyright= en-aut-name=NittaKaori en-aut-sei=Nitta en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UmedaHibiki en-aut-sei=Umeda en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriwakeKazuya en-aut-sei=Moriwake en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakedaSho en-aut-sei=Takeda en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KishimotoHiroyuki en-aut-sei=Kishimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KayanoMasashi en-aut-sei=Kayano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraShunsuke en-aut-sei=Nakamura en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KondoYuhei en-aut-sei=Kondo en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MiyakeEiki en-aut-sei=Miyake en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=17 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=24 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=25 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=RNA editing kn-keyword=RNA editing en-keyword=Liver metastasis kn-keyword=Liver metastasis en-keyword=Chemotherapy kn-keyword=Chemotherapy en-keyword=Biomarker kn-keyword=Biomarker en-keyword=Colorectal cancer kn-keyword=Colorectal cancer END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=158 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oncolytic virus-mediated p53 activation boosts the antitumor immunity of a p53-transduced dendritic cell vaccine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells (DCs) transduced with replication-deficient, wild-type human p53-expressing adenovirus Ad-p53 (Ad-p53 DCs) induce p53-targeting cytotoxic T lymphocytes (CTLs). However, the antitumor efficacy of Ad-p53 DCs is diminished by weak p53 immunogenicity in tumor cells and poor immune responses. We developed a p53-armed oncolytic adenovirus, OBP-702, to induce tumor-specific p53 expression and antitumor immune response, suggesting a role for OBP-702 in enhancing the antitumor efficacy of Ad-p53 DCs. The combined effect of Ad-p53 DCs and OBP-702 was investigated using murine colon cancer (CC) tumor models. Ad-p53 DCs were obtained by stimulating bone marrow-derived cells with granulocyte-macrophage colony-stimulating factor, interleukin-4, and Ad-p53. Subcutaneous tumor models of CT26 (p53 wild-type) and MC38 (p53 mutant-type) murine CC cell lines were used to evaluate the therapeutic potential of combination therapy in the terms of tumor growth, abscopal effect, antitumor immune response, and presentation of p53 peptides in tumor cells. Combination therapy with Ad-p53 DCs and OBP-702 significantly suppressed the growth of p53-intact CT26 tumors at treated and untreated sites by inducing tumor-infiltration of CD8+ CTLs and CD11c+ DCs. OBP-702-infected tumor cells presented human p53 epitopes in the context of major histocompatibility complex molecules, which were recognized by CTLs induced by Ad-p53 DCs. Combination therapy significantly suppressed the growth of p53-mutant MC38 tumors by activating the antitumor immune response. Our results suggest that OBP-702-mediated presentation of p53 epitopes on tumor cells enhances the antitumor efficacy of Ad-p53 DCs against murine CC tumors by attracting p53-targeting CTLs. en-copyright= kn-copyright= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuemoriKanto en-aut-sei=Suemori en-aut-mei=Kanto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkadaNaohiro en-aut-sei=Okada en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KajiwaraYoshinori en-aut-sei=Kajiwara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InoueHiroaki en-aut-sei=Inoue en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HashimotoNaoyuki en-aut-sei=Hashimoto en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Neutron Therapy Research Center, Okayama University Hospital kn-affil= affil-num=14 en-affil=Oncolys BioPharma, Inc kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=199 cd-vols= no-issue= article-no= start-page=108027 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=Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.
Materials and methods: Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan?Meier method.
Results: Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy?61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group?42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group?37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).
Conclusion: This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era. en-copyright= kn-copyright= en-aut-name=HorinouchiHidehito en-aut-sei=Horinouchi en-aut-mei=Hidehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurakamiHaruyasu en-aut-sei=Murakami en-aut-mei=Haruyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaHideyuki en-aut-sei=Harada en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SobueTomotaka en-aut-sei=Sobue en-aut-mei=Tomotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTomohiro en-aut-sei=Kato en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AtagiShinji en-aut-sei=Atagi en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TokitoTakaaki en-aut-sei=Tokito en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OizumiSatoshi en-aut-sei=Oizumi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SeikeMasahiro en-aut-sei=Seike en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=MioTadashi en-aut-sei=Mio en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SoneTakashi en-aut-sei=Sone en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwaoChikako en-aut-sei=Iwao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwaneTakeshi en-aut-sei=Iwane en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KotoRyo en-aut-sei=Koto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsuboiMasahiro en-aut-sei=Tsuboi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=3 en-affil=Division of Radiation Therapy, Shizuoka Cancer Center kn-affil= affil-num=4 en-affil=Division of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Hospital Organization Himeji Medical Cente kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center kn-affil= affil-num=10 en-affil=Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, National Hospital Organization Kyoto Medical Center kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=14 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=15 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=16 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=17 en-affil=Department of Thoracic Surgery, National Cancer Center Hospital East kn-affil= en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=Surgery kn-keyword=Surgery en-keyword=Adjuvant therapy kn-keyword=Adjuvant therapy en-keyword=Neoadjuvant therapy kn-keyword=Neoadjuvant therapy en-keyword=Chemoradiotherapy kn-keyword=Chemoradiotherapy en-keyword=Observational study kn-keyword=Observational study en-keyword=Retrospective study kn-keyword=Retrospective study END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=40 article-no= start-page=3355- end-page=3364 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plain language summary: tarlatamab for patients with previously treated small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=AhnMyung-Ju en-aut-sei=Ahn en-aut-mei=Myung-Ju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChoByoung Chul en-aut-sei=Cho en-aut-mei=Byoung Chul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KorantzisIppokratis en-aut-sei=Korantzis en-aut-mei=Ippokratis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MajemMargarita en-aut-sei=Majem en-aut-mei=Margarita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Juan-VidalOscar en-aut-sei=Juan-Vidal en-aut-mei=Oscar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HandzhievSabin en-aut-sei=Handzhiev en-aut-mei=Sabin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IzumiHiroki en-aut-sei=Izumi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LeeJong-Seok en-aut-sei=Lee en-aut-mei=Jong-Seok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DziadziuszkoRafal en-aut-sei=Dziadziuszko en-aut-mei=Rafal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WolfJ?rgen en-aut-sei=Wolf en-aut-mei=J?rgen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=BlackhallFiona en-aut-sei=Blackhall en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ReckMartin en-aut-sei=Reck en-aut-mei=Martin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AlvarezJean Bustamante en-aut-sei=Alvarez en-aut-mei=Jean Bustamante kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HummelHorst-Dieter en-aut-sei=Hummel en-aut-mei=Horst-Dieter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DingemansAnne-Marie C. en-aut-sei=Dingemans en-aut-mei=Anne-Marie C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SandsJacob en-aut-sei=Sands en-aut-mei=Jacob kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AkamatsuHiroaki en-aut-sei=Akamatsu en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OwonikokoTaofeek K. en-aut-sei=Owonikoko en-aut-mei=Taofeek K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=RamalingamSuresh S. en-aut-sei=Ramalingam en-aut-mei=Suresh S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=BorghaeiHossein en-aut-sei=Borghaei en-aut-mei=Hossein kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=JohnsonMelissa L. en-aut-sei=Johnson en-aut-mei=Melissa L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HuangShuang en-aut-sei=Huang en-aut-mei=Shuang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=MukherjeeSujoy en-aut-sei=Mukherjee en-aut-mei=Sujoy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MinochaMukul en-aut-sei=Minocha en-aut-mei=Mukul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=JiangTony en-aut-sei=Jiang en-aut-mei=Tony kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MartinezPablo en-aut-sei=Martinez en-aut-mei=Pablo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=AndersonErik S. en-aut-sei=Anderson en-aut-mei=Erik S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=Paz-AresLuis en-aut-sei=Paz-Ares en-aut-mei=Luis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Samsung Medical Center, Sungkyunkwan University School of Medicine kn-affil= affil-num=2 en-affil=Yonsei Cancer Center, Yonsei University College of Medicine kn-affil= affil-num=3 en-affil=Vall dfHebron University Hospital and Vall dfHebron Institute of Oncology kn-affil= affil-num=4 en-affil=Department of Medical Oncology, Saint Loukas Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Hospital de la Santa Creu i Sant Pau kn-affil= affil-num=7 en-affil= kn-affil= affil-num=8 en-affil=Klinische Abteilung f?r Pneumologie, Universit?tsklinikum Krems kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East kn-affil= affil-num=10 en-affil=Seoul National University Bundang Hospital kn-affil= affil-num=11 en-affil=Department of Oncology and Radiotherapy and Early Phase Clinical Trials Center, Medical University of Gdansk kn-affil= affil-num=12 en-affil=Department of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne kn-affil= affil-num=13 en-affil=Christie NHS Foundation Trust and University of Manchester kn-affil= affil-num=14 en-affil=Lungen Clinic, Airway Research Center North, German Center for Lung Research kn-affil= affil-num=15 en-affil=West Virginia University Health Sciences Center kn-affil= affil-num=16 en-affil=Translational Oncology?Early Clinical Trial Unit, Comprehensive Cancer Center Mainfranken and Bavarian Cancer Research Center, Universit?tsklinikum W?rzburg kn-affil= affil-num=17 en-affil=Department of Pulmonary Medicine, Erasmus MC Cancer Institute kn-affil= affil-num=18 en-affil=Dana?Farber Cancer Institute, Harvard Medical School kn-affil= affil-num=19 en-affil=Wakayama Medical University Hospital kn-affil= affil-num=20 en-affil=Division of Hematology?Oncology, Hillman Cancer Center, University of Pittsburgh Medical Center kn-affil= affil-num=21 en-affil=Winship Cancer Institute of Emory University kn-affil= affil-num=22 en-affil=Fox Chase Cancer Center kn-affil= affil-num=23 en-affil=Sarah Cannon Research Institute at Tennessee Oncology kn-affil= affil-num=24 en-affil=Amgen kn-affil= affil-num=25 en-affil=Amgen kn-affil= affil-num=26 en-affil=Amgen kn-affil= affil-num=27 en-affil=Amgen kn-affil= affil-num=28 en-affil=Amgen kn-affil= affil-num=29 en-affil=Amgen kn-affil= affil-num=30 en-affil=Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Complutense University and Ciberonc kn-affil= en-keyword=Clinical trials kn-keyword=Clinical trials en-keyword=DeLLphi-301 kn-keyword=DeLLphi-301 en-keyword=DLL3 kn-keyword=DLL3 en-keyword=Immunotherapy kn-keyword=Immunotherapy en-keyword=SCLC kn-keyword=SCLC en-keyword=Small cell lung cancer kn-keyword=Small cell lung cancer en-keyword=T cell kn-keyword=T cell en-keyword=Tarlatamab kn-keyword=Tarlatamab END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=24117 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250706 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Survival days of patients with metastatic spinal tumors of lung cancer requiring surgery: a prospective multicenter study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Surgery for metastatic spinal tumors has improved postoperative activities of daily living. A few studies reported on prognostic factors assessed in large multicenter prospective studies for metastatic spinal tumors of lung cancer origin. This study aimed to determine preoperative prognostic factors in patients undergoing surgery for metastatic spinal tumors associated with lung cancer. This prospective registry study included 74 patients diagnosed and operated with metastatic spine tumors derived from lung cancer in 39 high-volume cancer centers. We examined the postoperative survival period and the preoperative factors related to postoperative survival time. We conducted univariate and multivariate Cox regression analyses to determine preoperative prognostic factors. The mean postoperative survival period was 343 days. Multivariate Cox regression analysis revealed a higher feeding score of vitality index, indications for molecularly targeted therapy, and a higher mobility score of Barthel index as independent factors associated with postoperative survival time in metastatic spinal tumors derived from lung cancer. Patients with indications for molecular-targeted therapy and good vitality exhibited longer survival. These results may help in surgical selection for patients with metastatic spinal tumors derived from lung cancer. en-copyright= kn-copyright= en-aut-name=TakahashiTakuya en-aut-sei=Takahashi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraiTakashi en-aut-sei=Hirai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShirataniYuki en-aut-sei=Shiratani en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiAkinobu en-aut-sei=Suzuki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakutaniKenichiro en-aut-sei=Kakutani en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoSatoshi en-aut-sei=Kato en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TominagaHiroyuki en-aut-sei=Tominaga en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InoueHirokazu en-aut-sei=Inoue en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SawadaHirokatsu en-aut-sei=Sawada en-aut-mei=Hirokatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakegamiNorihiko en-aut-sei=Takegami en-aut-mei=Norihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakanishiKazuo en-aut-sei=Nakanishi en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakajimaHideaki en-aut-sei=Nakajima en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiharaMasayuki en-aut-sei=Ishihara en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OshigiriTsutomu en-aut-sei=Oshigiri en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FunayamaToru en-aut-sei=Funayama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IimuraTakuya en-aut-sei=Iimura en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TanishimaShinji en-aut-sei=Tanishima en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakashimaHiroaki en-aut-sei=Nakashima en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamabeDaisuke en-aut-sei=Yamabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HashimotoKo en-aut-sei=Hashimoto en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 ORCID= en-aut-name=FunabaMasahiro en-aut-sei=Funaba en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NagoshiNarihito en-aut-sei=Nagoshi en-aut-mei=Narihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KobayakawaKazu en-aut-sei=Kobayakawa en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YoshiiToshitaka en-aut-sei=Yoshii en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=WatanabeKazuyuki en-aut-sei=Watanabe en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamaeToshio en-aut-sei=Nakamae en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KaitoTakashi en-aut-sei=Kaito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=InoueGen en-aut-sei=Inoue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ImagamaShiro en-aut-sei=Imagama en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=WatanabeKota en-aut-sei=Watanabe en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=FuruyaTakeo en-aut-sei=Furuya en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Institute of Science Tokyo kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Institute of Science Tokyo kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Osaka Metropolitan University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=8 en-affil=Rehabilitation Center, Jichi Medical University Hospital kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Nihon University School of Medicine kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Mie University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Kawasaki Medical School kn-affil= affil-num=12 en-affil=Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=13 en-affil=Department of Orthopaedic surgery, Kansai Medical University Hospital kn-affil= affil-num=14 en-affil=Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine kn-affil= affil-num=15 en-affil=Department of Orthopaedic Surgery Institute of Medicine, University of Tsukuba kn-affil= affil-num=16 en-affil=Department of Orthopaedic Surgery, Dokkyo Medical University kn-affil= affil-num=17 en-affil=Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=18 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Orthopaedic Surgery, Iwate Medical University kn-affil= affil-num=20 en-affil=Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine kn-affil= affil-num=23 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=24 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=25 en-affil=Department of Orthopedic Surgery, Institute of Science Tokyo kn-affil= affil-num=26 en-affil=Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine kn-affil= affil-num=27 en-affil=Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=28 en-affil=Department of Orthopedic Surgery, Osaka University Graduate School of Medicine kn-affil= affil-num=29 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=30 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=31 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=32 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University kn-affil= en-keyword=Metastatic spinal tumor kn-keyword=Metastatic spinal tumor en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Postoperative survival period kn-keyword=Postoperative survival period en-keyword=Barthel index kn-keyword=Barthel index en-keyword=Vitality index kn-keyword=Vitality index en-keyword=Molecularly targeted therapy kn-keyword=Molecularly targeted therapy END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=5 article-no= start-page=594 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=Review Article: Diagnostic Paradigm Shift in Spine Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Meticulous clinical examination is essential for spinal disorders to utilize the diagnostic methods and technologies that strongly support physicians and enhance clinical practice. A significant change in the approach to diagnosing spinal disorders has occurred in the last three decades, which has enhanced a more nuanced understanding of spine pathology. Traditional radiographic methods such as conventional and functional X-rays and CT scans are still the first line in the diagnosis of spinal disorders due to their low cost and accessibility. As more advanced imaging technologies become increasingly available worldwide, there is a constantly increasing trend in MRI scans for detecting spinal pathologies and making treatment decisions. Not only do MRI scans have superior diagnostic capabilities, but they also assist surgeons in performing meticulous preoperative planning, making them currently the most widely used diagnostic tool for spinal disorders. Positron Emission Tomography (PET) can help detect inflammatory lesions, infections, and tumors. Other advanced diagnostic tools such as CT/MRI fusion image, Functional Magnetic Resonance Imaging (fMRI), Upright and Kinetic MRI, magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) could play an important role when it comes to detecting more special pathologies. However, some technical difficulties in the daily praxis and their high costs act as obstacles to their further spread. Integrating artificial intelligence and advancements in data analytics and virtual reality promises to enhance spinal proceduresf precision, safety, and efficacy. As these technologies continue to develop, they will play a critical role in transforming spinal surgery. This paradigm shift emphasizes the importance of continuous innovation and adaptability in improving the diagnosis and treatment of spinal disorders. en-copyright= kn-copyright= en-aut-name=LeventAras Efe en-aut-sei=Levent en-aut-mei=Aras Efe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaMasato en-aut-sei=Tanaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KumawatChetan en-aut-sei=Kumawat en-aut-mei=Chetan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HengChristian en-aut-sei=Heng en-aut-mei=Christian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NikolaosSalamalikis en-aut-sei=Nikolaos en-aut-mei=Salamalikis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LatkaKajetan en-aut-sei=Latka en-aut-mei=Kajetan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyamotoAkiyoshi en-aut-sei=Miyamoto en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KomatsubaraTadashi en-aut-sei=Komatsubara en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AratakiShinya en-aut-sei=Arataki en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OdaYoshiaki en-aut-sei=Oda en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShinoharaKensuke en-aut-sei=Shinohara en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= en-keyword=diagnosis kn-keyword=diagnosis en-keyword=spine surgery kn-keyword=spine surgery en-keyword=innovative technique kn-keyword=innovative technique en-keyword=MRI kn-keyword=MRI en-keyword=myelography kn-keyword=myelography END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=4 article-no= start-page=2286 end-page=2299 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Palliative Surgical Treatment for Spinal Metastases on the Patientfs Quality of Life With a Focus on the Segment of the Metastasis: A Prospective Multicenter Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Study Design: Prospective multicenter study.
Objectives: Palliative surgery is crucial for maintaining the quality of life (QOL) in patients with spinal metastases. This study aimed to compare the short-term outcomes of QOL after palliative surgery between patients with metastatic spinal tumors at different segments.
Methods: We prospectively compared the data of 203 patients with spinal metastases at 2-3 consecutive segments who were divided into the following three groups: cervical, patients with cervical spine lesions; thoracic, patients with upper?middle thoracic spine lesions; and TL/L/S, patients with lesions at the thoracolumbar junction and lumbar and sacral regions. Preoperative and postoperative EuroQol 5-dimension (EQ5D) 5-level were compared.
Results: All groups exhibited improvement in the Frankel grade, performance status, pain, Barthel index, EQ5D health state utility value (HSUV), and EQ5D visual analog scale (VAS) postoperatively. Although preoperative EQ5D HSUVs did not significantly differ between the groups (cervical, 0.461 } 0.291; thoracic, 0.321 } 0.292; and TL/L/S, 0.376 } 0.272), the thoracic group exhibited significantly lower postoperative EQ5D HSUVs than the other two groups (cervical, 0.653 } 0.233; thoracic, 0.513 } 0.252; and TL/L/S, 0.624 } 0.232). However, postoperative EQ5D VAS was not significantly different between the groups (cervical, 63.4 } 25.8; thoracic, 54.7 } 24.5; and TL/L/S, 61.7 } 21.9).
Conclusions: Palliative surgery for metastatic spinal tumors provided comparable QOL improvement, irrespective of the spinal segment involved. Patients with upper and middle thoracic spinal metastases had poorer QOL outcomes than those with metastases in other segments; however, sufficient QOL improvement was achieved. en-copyright= kn-copyright= en-aut-name=SegiNaoki en-aut-sei=Segi en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakashimaHiroaki en-aut-sei=Nakashima en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoSadayuki en-aut-sei=Ito en-aut-mei=Sadayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OuchidaJun en-aut-sei=Ouchida en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShirataniYuki en-aut-sei=Shiratani en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimizuTakaki en-aut-sei=Shimizu en-aut-mei=Takaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzukiAkinobu en-aut-sei=Suzuki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TeraiHidetomi en-aut-sei=Terai en-aut-mei=Hidetomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KakutaniKenichiro en-aut-sei=Kakutani en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KandaYutaro en-aut-sei=Kanda en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TominagaHiroyuki en-aut-sei=Tominaga en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawamuraIchiro en-aut-sei=Kawamura en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiharaMasayuki en-aut-sei=Ishihara en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=PakuMasaaki en-aut-sei=Paku en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakahashiYohei en-aut-sei=Takahashi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FunabaMasahiro en-aut-sei=Funaba en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FunayamaToru en-aut-sei=Funayama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakajimaHideaki en-aut-sei=Nakajima en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AkedaKoji en-aut-sei=Akeda en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HiraiTakashi en-aut-sei=Hirai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=InoueHirokazu en-aut-sei=Inoue en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=NakanishiKazuo en-aut-sei=Nakanishi en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FunaoHaruki en-aut-sei=Funao en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OshigiriTsutomu en-aut-sei=Oshigiri en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=OtsukiBungo en-aut-sei=Otsuki en-aut-mei=Bungo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KobayakawaKazu en-aut-sei=Kobayakawa en-aut-mei=Kazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TanishimaShinji en-aut-sei=Tanishima en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=HashimotoKo en-aut-sei=Hashimoto en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=IimuraTakuya en-aut-sei=Iimura en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SawadaHirokatsu en-aut-sei=Sawada en-aut-mei=Hirokatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 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=31 ORCID= en-aut-name=ManabeHiroaki en-aut-sei=Manabe en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=IwaiChizuo en-aut-sei=Iwai en-aut-mei=Chizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=YamabeDaisuke en-aut-sei=Yamabe en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=HiyamaAkihiko en-aut-sei=Hiyama en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=SekiShoji en-aut-sei=Seki en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=GotoYuta en-aut-sei=Goto en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=MiyazakiMasashi en-aut-sei=Miyazaki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=WatanabeKazuyuki en-aut-sei=Watanabe en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=NakamaeToshio en-aut-sei=Nakamae en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=KaitoTakashi en-aut-sei=Kaito en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=NagoshiNarihito en-aut-sei=Nagoshi en-aut-mei=Narihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=KatoSatoshi en-aut-sei=Kato en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=WatanabeKota en-aut-sei=Watanabe en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=ImagamaShiro en-aut-sei=Imagama en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=InoueGen en-aut-sei=Inoue en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=FuruyaTakeo en-aut-sei=Furuya en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Chiba University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Osaka Metropolitan University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Osaka Metropolitan University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Kansai Medial University Hospital kn-affil= affil-num=14 en-affil=Department of Orthopaedic Surgery, Kansai Medial University Hospital kn-affil= affil-num=15 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=16 en-affil=Department of Orthopaedics Surgery, Yamaguchi University Graduate school of Medicine kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Institute of Medicine, University of Tsukuba kn-affil= affil-num=18 en-affil=Department of Orthopaedics and Rehabilitation Medicine, University of Fukui Faculty of Medical Sciences kn-affil= affil-num=19 en-affil=Department of Orthopaedic Surgery, Mie University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Orthopedic Surgery, Tokyo Medical and Dental University kn-affil= affil-num=21 en-affil=Rehabilitation Center, Jichi Medical University Hospital kn-affil= affil-num=22 en-affil=Department of Orthopaedic Surgery, Kawasaki Medical School kn-affil= affil-num=23 en-affil=Department of Orthopaedic Surgery, International University of Health and Welfare Narita Hospital kn-affil= affil-num=24 en-affil=Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine kn-affil= affil-num=25 en-affil=Department of Orthopaedic Surgery, Kyoto University Hospital kn-affil= affil-num=26 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=27 en-affil=Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=28 en-affil=Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=29 en-affil=Department of Orthopaedic Surgery, Dokkyo Medical University kn-affil= affil-num=30 en-affil=Department of Orthopaedic Surgery, Nihon University School of Medicine kn-affil= affil-num=31 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=32 en-affil=Department of Orthopedics, Tokushima University kn-affil= affil-num=33 en-affil=Department of Orthopaedic Surgery, Gifu University Hospital kn-affil= affil-num=34 en-affil=Department of Orthopaedic Surgery, Iwate Medical University kn-affil= affil-num=35 en-affil=Department of Orthopaedic Surgery, Tokai University School of Medicine kn-affil= affil-num=36 en-affil=Department of Orthopaedic Surgery, University of Toyama kn-affil= affil-num=37 en-affil=Department of Orthopaedic Surgery, Nagoya City University kn-affil= affil-num=38 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Oita University kn-affil= affil-num=39 en-affil=Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine kn-affil= affil-num=40 en-affil=Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=41 en-affil=Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine kn-affil= affil-num=42 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=43 en-affil=Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=44 en-affil=Department of Orthopaedic Surgery, Keio University kn-affil= affil-num=45 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=46 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=47 en-affil=Department of Orthopaedic Surgery, Chiba University Hospital kn-affil= en-keyword=spinal metastasis kn-keyword=spinal metastasis en-keyword=metastasis segment kn-keyword=metastasis segment en-keyword=palliative surgery kn-keyword=palliative surgery en-keyword=quality of life kn-keyword=quality of life en-keyword=activities of daily living kn-keyword=activities of daily living en-keyword=pain kn-keyword=pain en-keyword=anxiety kn-keyword=anxiety END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=23 article-no= start-page=2715 end-page= 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= kn-title=Predicting Surgical Site Infections in Spine Surgery: Association of Postoperative Lymphocyte Reduction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Postoperative lymphopenia is reported as an excellent indicator to predict surgical-site infection (SSI) after spine surgery. However, there is still controversy concerning which serological markers can predict spinal SSI. This study aims to evaluate excellent and early indicators for detecting SSI, focusing on spine instrumented surgery. Materials and Methods: This study included 268 patients who underwent spinal instrumented surgery from January 2022 to December 2023 (159 female and 109 male, average 62.9 years). The SSI group included 20 patients, and the non-SSI group comprised 248 patients. Surgical time, intraoperative blood loss, and glycemic levels were measured in both groups. The complete blood cell counts, differential counts, albumin, and C-reactive protein (CRP) levels were measured pre-surgery and postoperative on Days 1, 3, and 7. In comparing the groups, the Mann?Whitney U test analysis was used for continuous variables, while the chi-squared test and Fisherfs exact test were used for dichotomous variables. Results: The incidence of SSI after spinal instrumentation was 7.46% and was relatively higher in scoliosis surgery. The SSI group had significantly longer surgical times (248 min vs. 180 min, p = 0.0004) and a higher intraoperative blood loss (772 mL vs. 372 mL, p < 0.0001) than the non-SSI group. In the SSI group, the Day 3 (10.5 } 6.2% vs. 13.8 } 6.0%, p = 0.012) and Day 7 (14.4 } 4.8% vs. 18.8 } 7.1%, p = 0.012) lymphocyte ratios were lower than the non-SSI group. Albumin levels on Day 1 in the SSI group were lower than in the non-SSI group (2.94 } 0.30 mg/dL vs. 3.09 } 0.38 mg/dL, p = 0.045). There is no difference in CRP and lymphocyte count between the two groups. Conclusions: SSI patients had lower lymphocyte percentages than non-SSI patients, which was a risk factor for SSI, with constant high inflammation. The Day 3 lymphocyte percentage may predict SSI after spinal instrumented surgery. en-copyright= kn-copyright= en-aut-name=MiyamotoAkiyoshi en-aut-sei=Miyamoto en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaMasato en-aut-sei=Tanaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FloresAngel Oscar Paz en-aut-sei=Flores en-aut-mei=Angel Oscar Paz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YuDongwoo en-aut-sei=Yu en-aut-mei=Dongwoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=JainMukul en-aut-sei=Jain en-aut-mei=Mukul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HengChristan en-aut-sei=Heng en-aut-mei=Christan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KomatsubaraTadashi en-aut-sei=Komatsubara en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AratakiShinya en-aut-sei=Arataki en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OdaYoshiaki en-aut-sei=Oda en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShinoharaKensuke en-aut-sei=Shinohara en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= en-keyword=surgical site infection kn-keyword=surgical site infection en-keyword=spine surgery kn-keyword=spine surgery en-keyword=instrumentation kn-keyword=instrumentation en-keyword=diagnosis kn-keyword=diagnosis en-keyword=lymphocyte kn-keyword=lymphocyte END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=209 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exercise hemodynamic evaluation in the management of dasatinib-related pulmonary arterial hypertension: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Dasatinib-related pulmonary arterial hypertension is a rare complication of chronic therapy for hematological malignancies. Pulmonary hypertension often persists despite drug discontinuation and might require vasodilators. Normalizing pulmonary hemodynamics and avoiding the long-term use of vasodilators is challenging.
Case presentation Patient was a 55-year-old Japanese man complaining of progressive dyspnea on effort and fatigue. He had a history of hypertension and chronic myeloid leukemia treated with dasatinib. He was diagnosed with dasatinib-related pulmonary arterial hypertension by a right heart catheterization at rest, demonstrating a mean pulmonary artery pressure of 31 mmHg and a normal pulmonary arterial wedge pressure of 6 mmHg. Symptoms and hemodynamics significantly improved after the discontinuation of dasatinib and the initiation of upfront combination therapy of vasodilators. An exercise right heart catheterization, performed more than 2 years after the initiation of vasodilators, showed a mean pulmonary artery pressure of 15 mmHg at rest and 29 mmHg at peak exercise (normal reference value,? Conclusions The evaluation of pulmonary microcirculation by exercise right heart catheterization can be useful for withdrawing pulmonary vasodilators safely in the management of patients with dasatinib-related pulmonary arterial hypertension. en-copyright= kn-copyright= en-aut-name=YamashitaShuhei en-aut-sei=Yamashita en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraideTakahiro en-aut-sei=Hiraide en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiraishiYasuyuki en-aut-sei=Shiraishi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsumataYoshinori en-aut-sei=Katsumata en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KataokaMasaharu en-aut-sei=Kataoka en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukuiShogo en-aut-sei=Fukui en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawakamiMichiyuki en-aut-sei=Kawakami en-aut-mei=Michiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=OkamotoShinichiro en-aut-sei=Okamoto en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukudaKeiichi en-aut-sei=Fukuda en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IedaMasaki en-aut-sei=Ieda en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=4 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=6 en-affil=Department of Rehabilitation, Keio University Hospital kn-affil= affil-num=7 en-affil=Department of Rehabilitation, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology, Keio University School of Medicine kn-affil= affil-num=10 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=11 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= en-keyword=Case report kn-keyword=Case report en-keyword=Dasatinib kn-keyword=Dasatinib en-keyword=Drug-induced kn-keyword=Drug-induced en-keyword=Exercise-induced pulmonary hypertension kn-keyword=Exercise-induced pulmonary hypertension en-keyword=Pulmonary arterial hypertension kn-keyword=Pulmonary arterial hypertension END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=2 article-no= start-page=euaf024 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SCN5A variant type-dependent risk prediction in Brugada syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims The variant in SCN5A with the loss of function (LOF) effect in the cardiac Na+ channel (Nav1.5) is the definitive cause for Brugada syndrome (BrS), and the functional analysis data revealed that LOF variants are associated with poor prognosis. However, which variant types (e.g. missense or non-missense) affect the prognoses of those variant carriers remain unelucidated.
Methods and results We defined SCN5A LOF variants as all non-missense and missense variants that produce peak INa < 65% of wild-type previously confirmed by patch-clamp studies. The study population consisted of 76 Japanese BrS patients (74% patients were male and the median age [IQR] at diagnosis was 28 [14?45] years) with LOF type of SCN5A variants: 40 with missense and 36 with non-missense variants. Non-missense variant carriers presented significantly more severe cardiac conduction disorder compared to the missense variant carriers. During follow-up periods of 9.0 [5.0?14.0] years, compared to missense variants, non-missense variants were significant risk factors of lifetime lethal arrhythmia events (LAEs) (P = 0.023). When focusing only on the missense variants that produce no peak INa, these missense variant carriers exhibited the same clinical outcomes as those with non-missense (log-rank P = 0.325). After diagnosis, however, both variant types were comparable in risk of LAEs (P = 0.155).
Conclusion We identified, for the first time, that SCN5A non-missense variants were associated with higher probability of LAE than missense variants in BrS patients though it did not change significantly after diagnosis. en-copyright= kn-copyright= en-aut-name=AizawaTakanori en-aut-sei=Aizawa en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakiyamaTakeru en-aut-sei=Makiyama en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangHai en-aut-sei=Huang en-aut-mei=Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImamuraTomohiko en-aut-sei=Imamura en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuyamaMegumi en-aut-sei=Fukuyama en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SonodaKeiko en-aut-sei=Sonoda en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatoKoichi en-aut-sei=Kato en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraYuko en-aut-sei=Nakamura en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HoshinoKenji en-aut-sei=Hoshino en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OzawaJunichi en-aut-sei=Ozawa en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SuzukiHiroshi en-aut-sei=Suzuki en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YasudaKazushi en-aut-sei=Yasuda en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AokiHisaaki en-aut-sei=Aoki en-aut-mei=Hisaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KuritaTakashi en-aut-sei=Kurita en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YoshidaYoko en-aut-sei=Yoshida en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SuzukiTsugutoshi en-aut-sei=Suzuki en-aut-mei=Tsugutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakamuraYoshihide en-aut-sei=Nakamura en-aut-mei=Yoshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OgawaYoshiharu en-aut-sei=Ogawa en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamagamiShintaro en-aut-sei=Yamagami en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FukudaMasakazu en-aut-sei=Fukuda en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OnoMakoto en-aut-sei=Ono en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KondoHidekazu en-aut-sei=Kondo en-aut-mei=Hidekazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=TakahashiNaohiko en-aut-sei=Takahashi en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=OhnoSeiko en-aut-sei=Ohno en-aut-mei=Seiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakagawaYoshihisa en-aut-sei=Nakagawa en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=OnoKoh en-aut-sei=Ono en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HorieMinoru en-aut-sei=Horie en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine , 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 , kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Medical Genome Center, National Cerebral and Cardiovascular Center kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=Department of Public Health, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Tsuchiura Kyodo General Hospital kn-affil= affil-num=10 en-affil=Department of Cardiology, Saitama Childrenfs Medical Center kn-affil= affil-num=11 en-affil=Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=12 en-affil=Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital kn-affil= affil-num=13 en-affil=Department of Pediatric Cardiology, Aichi Childrenfs Health and Medical Center kn-affil= affil-num=14 en-affil=Department of Pediatric Cardiology, Osaka Womenfs and Childrenfs Hospital kn-affil= affil-num=15 en-affil=Division of Cardiovascular Center, Kindai University School of Medicine kn-affil= affil-num=16 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=17 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=18 en-affil=Division of Pediatric Cardiology and Electrophysiology, Osaka City General Hospital kn-affil= affil-num=19 en-affil=Division of Cardiology, Hyogo Prefectural Kobe Childrenfs Hospital kn-affil= affil-num=20 en-affil=Department of Cardiology, Tenri Hospital kn-affil= affil-num=21 en-affil=Department of Cardiovascular Therapeutics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=22 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=24 en-affil=Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=25 en-affil=Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University kn-affil= affil-num=26 en-affil=Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University kn-affil= affil-num=27 en-affil=Medical Genome Center, National Cerebral and Cardiovascular Center kn-affil= affil-num=28 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= affil-num=29 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=30 en-affil=Department of Cardiovascular Medicine, Shiga University of Medical Science kn-affil= en-keyword=Brugada syndrome kn-keyword=Brugada syndrome en-keyword=SCN5A kn-keyword=SCN5A en-keyword=Lethal arrhythmia event kn-keyword=Lethal arrhythmia event en-keyword=Variant type kn-keyword=Variant type en-keyword=Loss of function kn-keyword=Loss of function END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=2 article-no= start-page=395 end-page=412.e6 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tissue-level oscillation is achieved by tissue-intrinsic clocks along with network-dependent signals originating from distal organs and organismal behavior. Yet, it remains unexplored whether maternal circadian rhythms during pregnancy influence fetal rhythms and impact long-term susceptibility to dietary challenges in offspring. Here, we demonstrate that circadian disruption during pregnancy decreased placental and neonatal weight yet retained transcriptional and structural maturation. Intriguingly, diet-induced obesity was exacerbated in parallel with arrhythmic feeding behavior, hypothalamic leptin resistance, and hepatic circadian reprogramming in offspring of chronodisrupted mothers. In utero circadian desynchrony altered the phase-relationship between the mother and fetus and impacted placental efficiency. Temporal feeding restriction in offspring failed to fully prevent obesity, whereas the circadian alignment of caloric restriction with the onset of the active phase virtually ameliorated the phenotype. Thus, maternal circadian rhythms during pregnancy confer adaptive properties to metabolic functions in offspring and provide insights into the developmental origins of health and disease. en-copyright= kn-copyright= en-aut-name=YaoNa en-aut-sei=Yao en-aut-mei=Na kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinouchiKenichiro en-aut-sei=Kinouchi en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatohManami en-aut-sei=Katoh en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AshtianiKousha Changizi en-aut-sei=Ashtiani en-aut-mei=Kousha Changizi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbdelkarimSherif en-aut-sei=Abdelkarim en-aut-mei=Sherif kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimotoHiroyuki en-aut-sei=Morimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TorimitsuTakuto en-aut-sei=Torimitsu en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KozumaTakahide en-aut-sei=Kozuma en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwaharaAkihide en-aut-sei=Iwahara en-aut-mei=Akihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KosugiShotaro en-aut-sei=Kosugi en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KomuroJin en-aut-sei=Komuro en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KatoKyosuke en-aut-sei=Kato en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TonomuraShun en-aut-sei=Tonomura en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakamuraToshifumi en-aut-sei=Nakamura en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItohArata en-aut-sei=Itoh en-aut-mei=Arata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamaguchiShintaro en-aut-sei=Yamaguchi en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YoshinoJun en-aut-sei=Yoshino en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IrieJunichiro en-aut-sei=Irie en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HashimotoHisayuki en-aut-sei=Hashimoto en-aut-mei=Hisayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SatohAkiko en-aut-sei=Satoh en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MikamiYohei en-aut-sei=Mikami en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=UchidaShusaku en-aut-sei=Uchida en-aut-mei=Shusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=UekiTakatoshi en-aut-sei=Ueki en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NomuraSeitaro en-aut-sei=Nomura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=BaldiPierre en-aut-sei=Baldi en-aut-mei=Pierre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=HayashiKaori en-aut-sei=Hayashi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=ItohHiroshi en-aut-sei=Itoh en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Computer Science, University of California kn-affil= affil-num=5 en-affil=Department of Computer Science, University of California kn-affil= affil-num=6 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=7 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=10 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=11 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=12 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=13 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=16 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=17 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=19 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=20 en-affil=Department of Cardiovascular Medicine, Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=21 en-affil=Department of Integrative Physiology, Institute of Development, Aging and Cancer, Tohoku University kn-affil= affil-num=22 en-affil=Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=23 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=24 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=25 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=26 en-affil=Department of Computer Science, University of California kn-affil= affil-num=27 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=28 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= en-keyword=circadian rhythm kn-keyword=circadian rhythm en-keyword=metabolism kn-keyword=metabolism en-keyword=circadian clock kn-keyword=circadian clock en-keyword=pregnancy kn-keyword=pregnancy en-keyword=developmental origins of health and disease kn-keyword=developmental origins of health and disease en-keyword=obesity kn-keyword=obesity en-keyword=leptin kn-keyword=leptin en-keyword=time-restricted feeding kn-keyword=time-restricted feeding en-keyword=caloric restriction kn-keyword=caloric restriction en-keyword=eating behavior kn-keyword=eating behavior END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002112 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Animal dsRNA and ssRNA(?) Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=RNA viruses are ubiquitous in the environment and are important pathogens of humans, animals and plants. In 2024, the International Committee on Taxonomy of Viruses Animal dsRNA and ssRNA(?) Viruses Subcommittee submitted 18 taxonomic proposals for consideration. These proposals expanded the known virosphere by classifying 9 new genera and 88 species for newly detected virus genomes. Of note, newly established species expand the large family of Rhabdoviridae to 580 species. A new species in the family Arenaviridae includes a virus detected in Antarctic fish with a unique split nucleoprotein ORF. Additionally, four new species were established for historically isolated viruses with previously unsequenced genomes. Furthermore, three species were abolished due to incomplete genome sequence information, and one family was moved from being unassigned in the phylum Negarnaviricota into a subphylum and order. Herein, we summarize the 18 ratified taxonomic proposals and the general features of the current taxonomy, thereby supporting public and animal health responses. en-copyright= kn-copyright= en-aut-name=HughesHolly R. en-aut-sei=Hughes en-aut-mei=Holly R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BallingerMatthew J. en-aut-sei=Ballinger en-aut-mei=Matthew J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BaoYiming en-aut-sei=Bao en-aut-mei=Yiming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BlasdellKim R. en-aut-sei=Blasdell en-aut-mei=Kim R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BrieseThomas en-aut-sei=Briese en-aut-mei=Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BrignoneJulia en-aut-sei=Brignone en-aut-mei=Julia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CarreraJean Paul en-aut-sei=Carrera en-aut-mei=Jean Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=De ConinckLander en-aut-sei=De Coninck en-aut-mei=Lander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=de SouzaWilliam Marciel en-aut-sei=de Souza en-aut-mei=William Marciel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=D?rrwaldRalf en-aut-sei=D?rrwald en-aut-mei=Ralf kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ErdinMert en-aut-sei=Erdin en-aut-mei=Mert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FooksAnthony R. en-aut-sei=Fooks en-aut-mei=Anthony R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ForbesKristian M. en-aut-sei=Forbes en-aut-mei=Kristian M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Freitas-Ast?aJuliana en-aut-sei=Freitas-Ast?a en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=GarciaJorge B. en-aut-sei=Garcia en-aut-mei=Jorge B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=GeogheganJemma L. en-aut-sei=Geoghegan en-aut-mei=Jemma L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GrimwoodRebecca M. en-aut-sei=Grimwood en-aut-mei=Rebecca M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HorieMasayuki en-aut-sei=Horie en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HyndmanTimothy H. en-aut-sei=Hyndman en-aut-mei=Timothy H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=JohneReimar en-aut-sei=Johne en-aut-mei=Reimar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KlenaJohn D. en-aut-sei=Klena en-aut-mei=John D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 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=25 ORCID= en-aut-name=KooninEugene V. en-aut-sei=Koonin en-aut-mei=Eugene V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KostygovAlexei Y. en-aut-sei=Kostygov en-aut-mei=Alexei Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=LetkoMichael en-aut-sei=Letko en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=LiJun-Min en-aut-sei=Li en-aut-mei=Jun-Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=LiuYiyun en-aut-sei=Liu en-aut-mei=Yiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=MartinMaria Laura en-aut-sei=Martin en-aut-mei=Maria Laura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MullNathaniel en-aut-sei=Mull en-aut-mei=Nathaniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NazarYael en-aut-sei=Nazar en-aut-mei=Yael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=NowotnyNorbert en-aut-sei=Nowotny en-aut-mei=Norbert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NunesM?rcio Roberto Teixeira en-aut-sei=Nunes en-aut-mei=M?rcio Roberto Teixeira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=?klandArnfinn Lodden en-aut-sei=?kland en-aut-mei=Arnfinn Lodden kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=RubbenstrothDennis en-aut-sei=Rubbenstroth en-aut-mei=Dennis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=RussellBrandy J. en-aut-sei=Russell en-aut-mei=Brandy J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=SchottEric en-aut-sei=Schott en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=SeifertStephanie en-aut-sei=Seifert en-aut-mei=Stephanie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SenCarina en-aut-sei=Sen en-aut-mei=Carina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=ShedroffElizabeth en-aut-sei=Shedroff en-aut-mei=Elizabeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=SironenTarja en-aut-sei=Sironen en-aut-mei=Tarja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=SmuraTeemu en-aut-sei=Smura en-aut-mei=Teemu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=TavaresCamila Prestes Dos Santos en-aut-sei=Tavares en-aut-mei=Camila Prestes Dos Santos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=TeshRobert B. en-aut-sei=Tesh en-aut-mei=Robert B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=TilstonNatasha L. en-aut-sei=Tilston en-aut-mei=Natasha L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=TordoNo?l en-aut-sei=Tordo en-aut-mei=No?l kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=VasilakisNikos en-aut-sei=Vasilakis en-aut-mei=Nikos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=WangFei en-aut-sei=Wang en-aut-mei=Fei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=WhitmerShannon L.M. en-aut-sei=Whitmer en-aut-mei=Shannon L.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=WolfYuri I. en-aut-sei=Wolf en-aut-mei=Yuri I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=XiaHan en-aut-sei=Xia en-aut-mei=Han kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=YeGong-Yin en-aut-sei=Ye en-aut-mei=Gong-Yin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=YeZhuangxin en-aut-sei=Ye en-aut-mei=Zhuangxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=YurchenkoVyacheslav en-aut-sei=Yurchenko en-aut-mei=Vyacheslav kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=ZhaoMingli en-aut-sei=Zhao en-aut-mei=Mingli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= affil-num=1 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=2 en-affil=Biological Sciences, Mississippi State University kn-affil= affil-num=3 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Consejo Nacional de Investigaciones Cient?ficas y T?cnicas (CONICET) and Instituto Nacional de Tecnolog?a Agropecuaria (INTA) kn-affil= affil-num=5 en-affil=CSIRO Health and Biosecurity kn-affil= affil-num=6 en-affil=Center for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University kn-affil= affil-num=7 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=8 en-affil=Instituto Conmemorativo Gorgas de Estudios de la Salud kn-affil= affil-num=9 en-affil=Division of Clinical and Epidemiological Virology, KU Leuven kn-affil= affil-num=10 en-affil=Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky kn-affil= affil-num=11 en-affil=Instituto Nacional de Tecnolog?a Agropecuaria (INTA) kn-affil= affil-num=12 en-affil=QAAFI, The University of Queensland kn-affil= affil-num=13 en-affil=Robert Koch Institut kn-affil= affil-num=14 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=15 en-affil=Animal and Plant Health Agency (APHA) kn-affil= affil-num=16 en-affil=Department of Biological Sciences, University of Arkansas kn-affil= affil-num=17 en-affil=Embrapa Cassava and Fruits kn-affil= affil-num=18 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=19 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=20 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=21 en-affil=Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University kn-affil= affil-num=22 en-affil=School of Veterinary Medicine, Murdoch University kn-affil= affil-num=23 en-affil=German Federal Institute for Risk Assessment kn-affil= affil-num=24 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=25 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=26 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=27 en-affil=University of Ostrava kn-affil= affil-num=28 en-affil=Institut Pasteur, Universit? Paris Cit?, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=29 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=30 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=31 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=32 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=33 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=34 en-affil=Department of Natural Sciences, Shawnee State University kn-affil= affil-num=35 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=36 en-affil=College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health kn-affil= affil-num=37 en-affil=Universidade Federal do Par? kn-affil= affil-num=38 en-affil=Pharmaq Analytiq kn-affil= affil-num=39 en-affil=Institute of Diagnostic Virology, Friedrich-Loeffler-Institut kn-affil= affil-num=40 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=41 en-affil=Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science kn-affil= affil-num=42 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=43 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=44 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=45 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=46 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=47 en-affil=Integrated Group of Aquaculture and Environmental Studies, Federal University of Paran? kn-affil= affil-num=48 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=49 en-affil=Department of Microbiology and Immunology, Indiana University School of Medicine kn-affil= affil-num=50 en-affil=Institut Pasteur kn-affil= affil-num=51 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=52 en-affil=University of Queensland kn-affil= affil-num=53 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=54 en-affil=North Carolina State University kn-affil= affil-num=55 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=56 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=57 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=58 en-affil=Institute of Insect Sciences, Zhejiang University kn-affil= affil-num=59 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=60 en-affil=University of Ostrava kn-affil= affil-num=61 en-affil=Department of Pathobiology and Population Sciences, Royal Veterinary College kn-affil= END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002114 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses from the Plant Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In March 2025, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote, newly proposed taxa were added to those under the mandate of the Plant Viruses Subcommittee. In brief, 1 new order, 3 new families, 6 new genera, 2 new subgenera and 206 new species were created. Some taxa were reorganized. Genus Cytorhabdovirus in the family Rhabdoviridae was abolished and its taxa were redistributed into three new genera Alphacytorhabdovirus, Betacytorhabdovirus and Gammacytorhabdovirus. Genus Waikavirus in the family Secoviridae was reorganized into two subgenera (Actinidivirus and Ritunrivirus). One family and four previously unaffiliated genera were moved to the newly established order Tombendovirales. Twelve species not assigned to a genus were abolished. To comply with the ICTV mandate of a binomial format for virus species, eight species were renamed. Demarcation criteria in the absence of biological information were defined in the genus Ilarvirus (family Bromoviridae). This article presents the updated taxonomy put forth by the Plant Viruses Subcommittee and ratified by the ICTV. en-copyright= kn-copyright= en-aut-name=RubinoLuisa en-aut-sei=Rubino en-aut-mei=Luisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AbrahamianPeter en-aut-sei=Abrahamian en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AnWenxia en-aut-sei=An en-aut-mei=Wenxia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArandaMiguel A. en-aut-sei=Aranda en-aut-mei=Miguel A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Ascencio-Iba?ezJos? T. en-aut-sei=Ascencio-Iba?ez en-aut-mei=Jos? T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BlouinArnaud G. en-aut-sei=Blouin en-aut-mei=Arnaud G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CandresseThierry en-aut-sei=Candresse en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CantoTomas en-aut-sei=Canto en-aut-mei=Tomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=CaoMengji en-aut-sei=Cao en-aut-mei=Mengji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=CarrJohn P. en-aut-sei=Carr en-aut-mei=John P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ChoWon Kyong en-aut-sei=Cho en-aut-mei=Won Kyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ConstableFiona en-aut-sei=Constable en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=DasguptaIndranil en-aut-sei=Dasgupta en-aut-mei=Indranil kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DigiaroMichele en-aut-sei=Digiaro en-aut-mei=Michele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DonaireLivia en-aut-sei=Donaire en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ElbeainoToufic en-aut-sei=Elbeaino en-aut-mei=Toufic kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FargetteDenis en-aut-sei=Fargette en-aut-mei=Denis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FilardoFiona en-aut-sei=Filardo en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FischerMatthias G. en-aut-sei=Fischer en-aut-mei=Matthias G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FontdevilaNuria en-aut-sei=Fontdevila en-aut-mei=Nuria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FoxAdrian en-aut-sei=Fox en-aut-mei=Adrian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=Freitas-AstuaJuliana en-aut-sei=Freitas-Astua en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FuchsMarc en-aut-sei=Fuchs en-aut-mei=Marc kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=GeeringAndrew D.W. en-aut-sei=Geering en-aut-mei=Andrew D.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=GhafariMahan en-aut-sei=Ghafari en-aut-mei=Mahan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=Hafr?nAnders en-aut-sei=Hafr?n en-aut-mei=Anders kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HammondJohn en-aut-sei=Hammond en-aut-mei=John kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=HammondRosemarie en-aut-sei=Hammond en-aut-mei=Rosemarie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=Hasi?w-JaroszewskaBeata en-aut-sei=Hasi?w-Jaroszewska en-aut-mei=Beata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=HebrardEugenie en-aut-sei=Hebrard en-aut-mei=Eugenie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=Hern?ndezCarmen en-aut-sei=Hern?ndez en-aut-mei=Carmen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=HilyJean-Michel en-aut-sei=Hily en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=HosseiniAhmed en-aut-sei=Hosseini en-aut-mei=Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=HullRoger en-aut-sei=Hull en-aut-mei=Roger kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=Inoue-NagataAlice K. en-aut-sei=Inoue-Nagata en-aut-mei=Alice K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=JordanRamon en-aut-sei=Jordan en-aut-mei=Ramon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 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=40 ORCID= en-aut-name=KreuzeJan F. en-aut-sei=Kreuze en-aut-mei=Jan F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=KubotaKenji en-aut-sei=Kubota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=LeisnerScott en-aut-sei=Leisner en-aut-mei=Scott kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=LettJean-Michel en-aut-sei=Lett en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=LiChengyu en-aut-sei=Li en-aut-mei=Chengyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=LiFan en-aut-sei=Li en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=LiJun Min en-aut-sei=Li en-aut-mei=Jun Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=L?pez-LambertiniPaola M. en-aut-sei=L?pez-Lambertini en-aut-mei=Paola M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=Lopez-MoyaJuan J. en-aut-sei=Lopez-Moya en-aut-mei=Juan J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=MaclotFrancois en-aut-sei=Maclot en-aut-mei=Francois kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=M?kinenKristiina en-aut-sei=M?kinen en-aut-mei=Kristiina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=MartinDarren en-aut-sei=Martin en-aut-mei=Darren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=MassartSebastien en-aut-sei=Massart en-aut-mei=Sebastien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=MillerW. Allen en-aut-sei=Miller en-aut-mei=W. Allen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=MohammadiMusa en-aut-sei=Mohammadi en-aut-mei=Musa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=MollovDimitre en-aut-sei=Mollov en-aut-mei=Dimitre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=MullerEmmanuelle en-aut-sei=Muller en-aut-mei=Emmanuelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=NagataTatsuya en-aut-sei=Nagata en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=Navas-CastilloJes?s en-aut-sei=Navas-Castillo en-aut-mei=Jes?s kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= en-aut-name=NeriyaYutaro en-aut-sei=Neriya en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=62 ORCID= en-aut-name=Ochoa-CoronaFrancisco M. en-aut-sei=Ochoa-Corona en-aut-mei=Francisco M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=63 ORCID= en-aut-name=OhshimaKazusato en-aut-sei=Ohshima en-aut-mei=Kazusato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=64 ORCID= en-aut-name=Pall?sVicente en-aut-sei=Pall?s en-aut-mei=Vicente kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=65 ORCID= en-aut-name=PappuHanu en-aut-sei=Pappu en-aut-mei=Hanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=66 ORCID= en-aut-name=PetrzikKarel en-aut-sei=Petrzik en-aut-mei=Karel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=67 ORCID= en-aut-name=PoogginMikhail en-aut-sei=Pooggin en-aut-mei=Mikhail kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=68 ORCID= en-aut-name=PrigigalloMaria Isabella en-aut-sei=Prigigallo en-aut-mei=Maria Isabella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=69 ORCID= en-aut-name=Ramos-Gonz?lezPedro L. en-aut-sei=Ramos-Gonz?lez en-aut-mei=Pedro L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=70 ORCID= en-aut-name=RibeiroSimone en-aut-sei=Ribeiro en-aut-mei=Simone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=71 ORCID= en-aut-name=Richert-P?ggelerKatja R. en-aut-sei=Richert-P?ggeler en-aut-mei=Katja R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=72 ORCID= en-aut-name=RoumagnacPhilippe en-aut-sei=Roumagnac en-aut-mei=Philippe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=73 ORCID= en-aut-name=RoyAvijit en-aut-sei=Roy en-aut-mei=Avijit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=74 ORCID= en-aut-name=SabanadzovicSead en-aut-sei=Sabanadzovic en-aut-mei=Sead kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=75 ORCID= en-aut-name=?af??ov?Dana en-aut-sei=?af??ov? en-aut-mei=Dana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=76 ORCID= en-aut-name=SaldarelliPasquale en-aut-sei=Saldarelli en-aut-mei=Pasquale kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=77 ORCID= en-aut-name=Sanfa?onH?l?ne en-aut-sei=Sanfa?on en-aut-mei=H?l?ne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=78 ORCID= en-aut-name=SarmientoCecilia en-aut-sei=Sarmiento en-aut-mei=Cecilia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=79 ORCID= en-aut-name=SasayaTakahide en-aut-sei=Sasaya en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=80 ORCID= en-aut-name=ScheetsKay en-aut-sei=Scheets en-aut-mei=Kay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=81 ORCID= en-aut-name=SchravesandeWillem E.W. en-aut-sei=Schravesande en-aut-mei=Willem E.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=82 ORCID= en-aut-name=SealSusan en-aut-sei=Seal en-aut-mei=Susan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=83 ORCID= en-aut-name=ShimomotoYoshifumi en-aut-sei=Shimomoto en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=84 ORCID= en-aut-name=S?meraMerike en-aut-sei=S?mera en-aut-mei=Merike kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=85 ORCID= en-aut-name=StavoloneLivia en-aut-sei=Stavolone en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=86 ORCID= en-aut-name=StewartLucy R. en-aut-sei=Stewart en-aut-mei=Lucy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=87 ORCID= en-aut-name=TeycheneyPierre-Yves en-aut-sei=Teycheney en-aut-mei=Pierre-Yves kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=88 ORCID= en-aut-name=ThomasJohn E. en-aut-sei=Thomas en-aut-mei=John E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=89 ORCID= en-aut-name=ThompsonJeremy R. en-aut-sei=Thompson en-aut-mei=Jeremy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=90 ORCID= en-aut-name=TiberiniAntonio en-aut-sei=Tiberini en-aut-mei=Antonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=91 ORCID= en-aut-name=TomitakaYasuhiro en-aut-sei=Tomitaka en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=92 ORCID= en-aut-name=TzanetakisIoannis en-aut-sei=Tzanetakis en-aut-mei=Ioannis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=93 ORCID= en-aut-name=UmberMarie en-aut-sei=Umber en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=94 ORCID= en-aut-name=UrbinoCica en-aut-sei=Urbino en-aut-mei=Cica kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=95 ORCID= en-aut-name=van den BurgHarrold A. en-aut-sei=van den Burg en-aut-mei=Harrold A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=96 ORCID= en-aut-name=Van der VlugtRen? A.A. en-aut-sei=Van der Vlugt en-aut-mei=Ren? A.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=97 ORCID= en-aut-name=VarsaniArvind en-aut-sei=Varsani en-aut-mei=Arvind kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=98 ORCID= en-aut-name=VerhageAdriaan en-aut-sei=Verhage en-aut-mei=Adriaan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=99 ORCID= en-aut-name=VillamorDan en-aut-sei=Villamor en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=100 ORCID= en-aut-name=von BargenSusanne en-aut-sei=von Bargen en-aut-mei=Susanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=101 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=102 ORCID= en-aut-name=WetzelThierry en-aut-sei=Wetzel en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=103 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=104 ORCID= en-aut-name=WylieStephen J. en-aut-sei=Wylie en-aut-mei=Stephen J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=105 ORCID= en-aut-name=YangCaixia en-aut-sei=Yang en-aut-mei=Caixia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=106 ORCID= en-aut-name=ZerbiniF. Murilo en-aut-sei=Zerbini en-aut-mei=F. Murilo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=107 ORCID= en-aut-name=ZhangSong en-aut-sei=Zhang en-aut-mei=Song kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=108 ORCID= affil-num=1 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=2 en-affil=USDA-ARS, BARC, National Germplasm Resources Laboratory kn-affil= affil-num=3 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=4 en-affil=Centro de Edafolog?a y Biolog?a Aplicada del Segura-CSIC kn-affil= affil-num=5 en-affil=Department of Molecular and Structural Biochemistry, North Carolina State University kn-affil= affil-num=6 en-affil=Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=7 en-affil=Plant Protection Department kn-affil= affil-num=8 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=9 en-affil=Margarita Salas Center for Biological Research (CIB-CSIC) Spanish Council for Scientific Research (CSIC) kn-affil= affil-num=10 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= affil-num=11 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=12 en-affil=Agriculture and Life Sciences Research Institute, Kangwon National University kn-affil= affil-num=13 en-affil=Agriculture Victoria Research, Department of Energy, Environment and Climate Action and School of Applied Systems Biology, La Trobe University kn-affil= affil-num=14 en-affil=University of Delhi South Campu kn-affil= affil-num=15 en-affil=Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=16 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=17 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=18 en-affil=Centro de Edafolog?a y Biolog?a Aplicada del Segura-CSIC kn-affil= affil-num=19 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=20 en-affil=Virus South Data kn-affil= affil-num=21 en-affil=Queensland Department of Primary Industries kn-affil= affil-num=22 en-affil=Max Planck Institute for Marine Microbiology kn-affil= affil-num=23 en-affil=Plant Protection Department kn-affil= affil-num=24 en-affil=Fera Science Ltd (Fera), York Biotech Campus kn-affil= affil-num=25 en-affil=Embrapa Cassava and Fruits, Brazilian Agricultural Research Corporation kn-affil= affil-num=26 en-affil=Plant Pathology, Cornell University kn-affil= affil-num=27 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=28 en-affil=Department of Biology, University of Oxford kn-affil= affil-num=29 en-affil=Swedish University of Agriculture kn-affil= affil-num=30 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=31 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory kn-affil= affil-num=32 en-affil=Institute of Plant Protection-NRI kn-affil= affil-num=33 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=34 en-affil=Instituto de Biolog?a Molecular y Celular de Plantas (IBMCP), Universitat Polit?cnica de Valencia-CSIC kn-affil= affil-num=35 en-affil=Institut Fran?ais de la Vigne et du Vin kn-affil= affil-num=36 en-affil=Vali-e-Asr University of Rafsanjan, Department of Plant Protection kn-affil= affil-num=37 en-affil=Retired from John Innes Centre kn-affil= affil-num=38 en-affil=Embrapa Hortali?as kn-affil= affil-num=39 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=40 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=41 en-affil=International Potato Center (CIP) kn-affil= affil-num=42 en-affil=Institut Pasteur, Universit? Paris Cit?, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=43 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=44 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=45 en-affil=Department of Biological Sciences, University of Toledo kn-affil= affil-num=46 en-affil=CIRAD, UMR PVBMT kn-affil= affil-num=47 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=48 en-affil=State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University kn-affil= affil-num=49 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=50 en-affil=Instituto de Patolog?a Vegetal (IPAVE), INTA, Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=51 en-affil=Centre for Research in Agricultural Genomics, CRAG (CSIC-IRTA-UAB-UB) kn-affil= affil-num=52 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=53 en-affil=Department of Agricultural Sciences, University of Helsinki kn-affil= affil-num=54 en-affil=Institute of Infectious Disease and Molecular Medicine, University of Cape Town kn-affil= affil-num=55 en-affil=Plant Pathology Laboratory, TERRA Gembloux Agro-Bio Tech, University of Liege kn-affil= affil-num=56 en-affil=Department of Plant Pathology, Entomology and Microbiology, Iowa State University kn-affil= affil-num=57 en-affil=Department of Plant Protection, Gorgan University of Agricultural Sciences and Natural Resources kn-affil= affil-num=58 en-affil=USDA-APHIS, Plant Protection and Quarantine kn-affil= affil-num=59 en-affil=CIRAD, AGAP Institut; AGAP Institut, University of Montpellier; CIRAD, INRAE kn-affil= affil-num=60 en-affil=Instituto de Ci?ncias Biol?gicas, Universidade de Bras?lia kn-affil= affil-num=61 en-affil=Instituto de Hortofruticultura Subtropical y Mediterr?nea gLa Mayorah (IHSM-UMA-CSIC), Consejo Superior de Investigaciones Cient?ficas kn-affil= affil-num=62 en-affil=Utsunomiya University kn-affil= affil-num=63 en-affil=Oklahoma State University, Institute for Biosecurity & Microbial Forensics kn-affil= affil-num=64 en-affil=Saga University kn-affil= affil-num=65 en-affil=Instituto de Biolog?a Molecular y Celular de Plantas (IBMCP), Universitat Polit?cnica de Valencia-CSIC kn-affil= affil-num=66 en-affil=Department of Plant Pathology, Washington State University kn-affil= affil-num=67 en-affil=Institute of Plant Molecular Biology kn-affil= affil-num=68 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD kn-affil= affil-num=69 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=70 en-affil=Applied Molecular Biology Laboratory, Instituto Biol?gico de S?o Paulo kn-affil= affil-num=71 en-affil=Embrapa Recursos Gen?ticos e Biotecnologia kn-affil= affil-num=72 en-affil=Julius K?hn Institute, Federal Research Centre for Cultivated Plants, Institute for Epidemiology and Pathogen Diagnostics kn-affil= affil-num=73 en-affil=CIRAD, UMR PHIM kn-affil= affil-num=74 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory, Beltsville, MD, USA kn-affil= affil-num=75 en-affil=Department of Agricultural Science and Plant Protection, Mississippi State University kn-affil= affil-num=76 en-affil=Department of Cell Biology and Genetics, Faculty of Science, Palack? University Olomouc kn-affil= affil-num=77 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=78 en-affil=Summerland Research and Development Centre, Agriculture and Agri-Food Canada kn-affil= affil-num=79 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=80 en-affil=Strategic Planning Headquarters, NARO kn-affil= affil-num=81 en-affil=Department of Plant Pathology, Ecology and Evolution, Oklahoma State University kn-affil= affil-num=82 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=83 en-affil=Natural Resources Institute, University of Greenwich kn-affil= affil-num=84 en-affil=Kochi Agricultural Research Center kn-affil= affil-num=85 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=86 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=87 en-affil=Currently unaffiliated kn-affil= affil-num=88 en-affil=CIRAD, UMR PVBMT & UMR PVBMT, Universit? de la R?union kn-affil= affil-num=89 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=90 en-affil=Plant Health and Environment Laboratory kn-affil= affil-num=91 en-affil=Council for Agricultural Research and Economics, Research Centre for Plant Protection and Certification kn-affil= affil-num=92 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=93 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=94 en-affil=INRAE, UR ASTRO kn-affil= affil-num=95 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=96 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=97 en-affil=Wageningen University and Research kn-affil= affil-num=98 en-affil=The Biodesign Center for Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State University kn-affil= affil-num=99 en-affil=Rijk Zwaan Breeding B.V. kn-affil= affil-num=100 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=101 en-affil=Humboldt-Universit?t zu Berlin, Thaer-Institute of Agricultural and Horticultural Sciences kn-affil= affil-num=102 en-affil=The University of Queensland kn-affil= affil-num=103 en-affil=Dienstleistungszentrum L?ndlicher Raum Rheinpfalz kn-affil= affil-num=104 en-affil=North Carolina State University kn-affil= affil-num=105 en-affil=Food Futures Institute, Murdoch University kn-affil= affil-num=106 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=107 en-affil=Dep. de Fitopatologia/BIOAGRO, Universidade Federal de Vi?osa kn-affil= affil-num=108 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=12 article-no= start-page=2429 end-page=2437 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Discovery of a Compound That Inhibits IRE1ƒ¿ S-Nitrosylation and Preserves the Endoplasmic Reticulum Stress Response under Nitrosative Stress en-subtitle= kn-subtitle= en-abstract= kn-abstract=Inositol-requiring enzyme 1ƒ¿ (IRE1ƒ¿) is a sensor of endoplasmic reticulum (ER) stress and drives ER stress response pathways. Activated IRE1ƒ¿ exhibits RNase activity and cleaves mRNA encoding X-box binding protein 1, a transcription factor that induces the expression of genes that maintain ER proteostasis for cell survival. Previously, we showed that IRE1ƒ¿ undergoes S-nitrosylation, a post-translational modification induced by nitric oxide (NO), resulting in reduced RNase activity. Therefore, S-nitrosylation of IRE1ƒ¿ compromises the response to ER stress, making cells more vulnerable. We conducted virtual screening and cell-based validation experiments to identify compounds that inhibit the S-nitrosylation of IRE1ƒ¿ by targeting nitrosylated cysteine residues. We ultimately identified a compound (1ACTA) that selectively inhibits the S-nitrosylation of IRE1ƒ¿ and prevents the NO-induced reduction of RNase activity. Furthermore, 1ACTA reduces the rate of NO-induced cell death. Our research identified S-nitrosylation as a novel target for drug development for IRE1ƒ¿ and provides a suitable screening strategy. en-copyright= kn-copyright= en-aut-name=KurogiHaruna en-aut-sei=Kurogi en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KubotaSho en-aut-sei=Kubota en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KumarAshutosh en-aut-sei=Kumar en-aut-mei=Ashutosh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiTakehiro en-aut-sei=Suzuki en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DohmaeNaoshi en-aut-sei=Dohmae en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SawadaDaisuke en-aut-sei=Sawada en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZhangKam Y.J. en-aut-sei=Zhang en-aut-mei=Kam Y.J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN kn-affil= affil-num=5 en-affil=Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=6 en-affil=Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=7 en-affil=Department of Fine Organic Synthesis, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN kn-affil= affil-num=9 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=9 article-no= start-page=2604 end-page=2611 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240830 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rethinking Thin-Layer Chromatography for Screening Technetium-99m Radiolabeled Polymer Nanoparticles en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thin-layer chromatography (TLC) is commonly employed to screen technetium-99m labeled polymer nanoparticle batches for unreduced pertechnetate and radio-colloidal impurities. Although this method is widely accepted, our findings applying radiolabeled PLGA/PLA?PEG nanoparticles underscore its lack of transferability between different settings and its limitations as a standalone quality control tool. While TLC profiles may appear similar for purified and radiocolloid containing nanoparticle formulations, their in vivo behavior can vary significantly, as demonstrated by discrepancies between TLC results and single-photon emission computed tomography (SPECT) and biodistribution data. This highlights the urgent need for a case-by-case evaluation of TLC methods for each specific nanoparticle type. Our study revealed that polymeric nanoparticles cannot be considered analytically uniform entities in the context of TLC analysis, emphasizing the complex interplay between nanoparticle composition, radiolabeling conditions, and subsequent biological behavior. en-copyright= kn-copyright= en-aut-name=SchorrKathrin en-aut-sei=Schorr en-aut-mei=Kathrin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Arias-LozaAnahi Paula en-aut-sei=Arias-Loza en-aut-mei=Anahi Paula kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LangJohannes en-aut-sei=Lang en-aut-mei=Johannes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=GoepferichAchim en-aut-sei=Goepferich en-aut-mei=Achim kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pharmaceutical Technology, University of Regensburg kn-affil= affil-num=2 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital W?rzburg kn-affil= affil-num=5 en-affil=Department of Pharmaceutical Technology, University of Regensburg kn-affil= affil-num=6 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Technology, University of Regensburg kn-affil= en-keyword=polymer nanoparticles kn-keyword=polymer nanoparticles en-keyword=direct 99mTc-labeling kn-keyword=direct 99mTc-labeling en-keyword=single-photon emission computed tomography kn-keyword=single-photon emission computed tomography en-keyword=radio-thin layer chromatography kn-keyword=radio-thin layer chromatography en-keyword=radiocolloids kn-keyword=radiocolloids END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=2 article-no= start-page=294 end-page=300 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluating the Patterns of FAPI Uptake in the Shoulder Joint: a Preliminary Study Comparing with FDG Uptake in Oncological Studies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Fibroblast activation protein inhibitor (FAPI) targeting PET has been introduced as a novel molecular imaging modality for visualizing cancer-associated fibroblasts. There have also been reports suggesting incidental findings of localized accumulation in the shoulder joints. However, further characterization in a larger patient cohort is still lacking.
Methods 77 consecutive patients (28 females; mean age, 63.1?}?11.6) who underwent Ga-68 FAPI-04 PET/CT for diagnosis of solid tumors were included. The incidence and localization of tracer uptake in shoulder joints were investigated and compared with available F-18 FDG scans serving as reference.
Results Ga-68 FAPI-04 uptake was evaluated in 77 patients (154 shoulder joints), of whom 54 subjects (108 shoulder joints) also had available F-18 FDG scans for head-to-head comparison. On FAPI-targeted imaging, 67/154 shoulders (43.5%) demonstrated increased radiotracer accumulation in target lesions, which were distributed as follows: acromioclavicular (AC) joints in 25/67 (37.3%), followed by glenohumeral and subacromial (GH?+?SA) joints in 23/67 (34.3%), or both (AC and GH?+?SA joints) in the remaining 19/67 (28.4%). Ga-68 FAPI-04 correlated with quantified F-18 FDG uptake (r?=?0.69, p? Conclusion Our study revealed focal accumulation of Ga-68 FAPI-04 in the shoulders, particularly in the AC joints, with higher uptake compared to the inflammatory-directed PET radiotracer F-18 FDG in oncological studies. As a result, further trials are warranted to investigate the potential of FAPI-directed molecular imaging in identifying chronic remodeling in shoulder joints. This could have implications for initiating anti-FAP targeted photodynamic therapy based on PET signal strength. en-copyright= kn-copyright= en-aut-name=MatsusakaYohji en-aut-sei=Matsusaka en-aut-mei=Yohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WernerRudolf A. en-aut-sei=Werner en-aut-mei=Rudolf A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SerflingSebastian E. en-aut-sei=Serfling en-aut-mei=Sebastian E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BuckAndreas K. en-aut-sei=Buck en-aut-mei=Andreas K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KosmalaAleksander en-aut-sei=Kosmala en-aut-mei=Aleksander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WeichAlexander en-aut-sei=Weich en-aut-mei=Alexander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of W?rzburg kn-affil= affil-num=2 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of W?rzburg kn-affil= affil-num=3 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of W?rzburg kn-affil= affil-num=4 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of W?rzburg kn-affil= affil-num=5 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of W?rzburg kn-affil= affil-num=6 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (CHFC), Molecular Imaging of the Heart, University Hospital of W?rzburg kn-affil= affil-num=8 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Fibroblast activation inhibitor kn-keyword=Fibroblast activation inhibitor en-keyword=Shoulder kn-keyword=Shoulder en-keyword=Acromioclavicular joints kn-keyword=Acromioclavicular joints en-keyword=F-18 fluorodeoxyglucose kn-keyword=F-18 fluorodeoxyglucose en-keyword=Positron emission tomography kn-keyword=Positron emission tomography en-keyword=FAP kn-keyword=FAP en-keyword=Ga-68 FAPI-04 kn-keyword=Ga-68 FAPI-04 en-keyword=Rheumatoid arthritis kn-keyword=Rheumatoid arthritis en-keyword=Osteoarthritis kn-keyword=Osteoarthritis END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=6 article-no= start-page=466 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial Intelligence Approach in Machine Learning-Based Modeling and Networking of the Coronavirus Pathogenesis Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=The coronavirus pathogenesis pathway, which consists of severe acute respiratory syndrome (SARS) coronavirus infection and signaling pathways, including the interferon pathway, the transforming growth factor beta pathway, the mitogen-activated protein kinase pathway, the apoptosis pathway, and the inflammation pathway, is activated upon coronaviral infection. An artificial intelligence approach based on machine learning was utilized to develop models with images of the coronavirus pathogenesis pathway to predict the activation states. Data on coronaviral infection held in a database were analyzed with Ingenuity Pathway Analysis (IPA), a network pathway analysis tool. Data related to SARS coronavirus 2 (SARS-CoV-2) were extracted from more than 100,000 analyses and datasets in the IPA database. A total of 27 analyses, including nine analyses of SARS-CoV-2-infected human-induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes and fibroblasts, and a total of 22 analyses of SARS-CoV-2-infected lung adenocarcinoma (LUAD), were identified as being related to ghumanh and gSARS coronavirus 2h in the database. The coronavirus pathogenesis pathway was activated in SARS-CoV-2-infected iPSC-derived cells and LUAD cells. A prediction model was developed in Python 3.11 using images of the coronavirus pathogenesis pathway under different conditions. The prediction model of activation states of the coronavirus pathogenesis pathway may aid in treatment identification. en-copyright= kn-copyright= en-aut-name=TanabeShihori en-aut-sei=Tanabe en-aut-mei=Shihori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=QuaderSabina en-aut-sei=Quader en-aut-mei=Sabina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoRyuichi en-aut-sei=Ono en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoAkihisa en-aut-sei=Yamamoto en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaMotohiro en-aut-sei=Kojima en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PerkinsEdward J. en-aut-sei=Perkins en-aut-mei=Edward J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion kn-affil= affil-num=3 en-affil=Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Mechanical Systems Engineering, Graduate School of Systems Design Tokyo Metropolitan University kn-affil= affil-num=6 en-affil=Department of Surgical Pathology, Kyoto Prefecture University of Medicine kn-affil= affil-num=7 en-affil=US Army Engineer Research and Development Center kn-affil= affil-num=8 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=coronavirus kn-keyword=coronavirus en-keyword=coronaviral infection kn-keyword=coronaviral infection en-keyword=machine learning kn-keyword=machine learning en-keyword=pathway analysis kn-keyword=pathway analysis en-keyword=predictionmodel kn-keyword=predictionmodel en-keyword=molecular network kn-keyword=molecular network en-keyword=molecular pathway image kn-keyword=molecular pathway image en-keyword=network analysis kn-keyword=network analysis END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=11 article-no= start-page=4984 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cardiomyopathies are a heterogeneous group of heart muscle diseases that can lead to heart failure, arrhythmias, and sudden cardiac death. Traditional animal models and in vitro systems have limitations in replicating the complex pathology of human cardiomyopathies. Induced pluripotent stem cells (iPSCs) offer a transformative platform by enabling the generation of patient-specific cardiomyocytes, thus opening new avenues for disease modeling, drug discovery, and regenerative therapy. This process involves reprogramming somatic cells into iPSCs and subsequently differentiating them into functional cardiomyocytes, which can be characterized using techniques such as electrophysiology, contractility assays, and gene expression profiling. iPSC-derived cardiomyocyte (iPSC-CM) platforms are also being explored for drug screening and personalized medicine, including high-throughput testing for cardiotoxicity and the identification of patient-tailored therapies. While iPSC-CMs already serve as valuable models for understanding disease mechanisms and screening drugs, ongoing advances in maturation and bioengineering are bringing iPSC-based therapies closer to clinical application. Furthermore, the integration of multi-omics approaches and artificial intelligence (AI) is enhancing the predictive power of iPSC models. iPSC-based technologies are paving the way for a new era of personalized cardiology, with the potential to revolutionize the management of cardiomyopathies through patient-specific insights and regenerative strategies. 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=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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 Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=induced pluripotent stem cells kn-keyword=induced pluripotent stem cells en-keyword=cardiomyopathy kn-keyword=cardiomyopathy en-keyword=disease modeling kn-keyword=disease modeling en-keyword=drug screening kn-keyword=drug screening en-keyword=regenerative therapy kn-keyword=regenerative therapy END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=13 article-no= start-page=7238 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250627 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protective Effects of the Ethyl Acetate Fraction of Distylium racemosum Against Metabolic Dysfunction-Associated Steatohepatitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as non-alcoholic steatohepatitis (NASH), which is a progressive non-alcoholic fatty liver disease, is accompanied by hepatic steatosis, inflammation, and fibrosis. Despite its increasing prevalence, available treatment options for MASH are limited. Here, we investigated the protective effects of the Distylium racemosum ethyl acetate fraction (DRE) using MASH models and explored its key physiologically active components. Palmitic acid (PA)-induced AML12 hepatocytes and high-fat methionine- and choline-deficient-fed C57BL/6 mice were used as MASH models. Lipid accumulation was evaluated via triglyceride measurement, oil red O staining, and histological analysis. Lipid accumulation, inflammation, and fibrosis-associated gene expression were evaluated via real-time polymerase chain reaction. The physiologically active components of DRE were identified via high-performance liquid chromatography. Lipid accumulation and triglyceride levels were significantly reduced in PA-treated AML12 cells following DRE treatment. Additionally, DRE inhibited the expression of genes involved in lipogenesis (FAS and SREBP1c), inflammation (CD68, IL-6, and MCP-1), and fibrosis (COL1A1, COL1A2, and TIMP1). DRE reduced the liver weight, liver-to-body weight ratio, and hepatic steatosis in MASH model mice. It increased carnitine palmitoyltransferase-1 levels and decreased CD36 and transforming growth factor-ƒÀ levels in the MASH mouse liver. High-performance liquid chromatography revealed that the extract contained rutin flavonoid family members. Overall, DRE was involved in lipid metabolism, inflammation, and fibrosis regulation, exerting potent hepatoprotective effects partly attributed to rutin and serving as a potential preventive candidate for MASH. en-copyright= kn-copyright= en-aut-name=LeeYoung-Hyeon en-aut-sei=Lee en-aut-mei=Young-Hyeon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YeoMin-Ho en-aut-sei=Yeo en-aut-mei=Min-Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChangKyung-Soo en-aut-sei=Chang en-aut-mei=Kyung-Soo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoonWeon-Jong en-aut-sei=Yoon en-aut-mei=Weon-Jong 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= en-aut-name=KimJongwan en-aut-sei=Kim en-aut-mei=Jongwan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimHye-Ran en-aut-sei=Kim en-aut-mei=Hye-Ran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=2 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=3 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=4 en-affil=Clean Bio Business Division, Biodiversity Research Institute (JBRI), Jeju Technopark (JTP) kn-affil= affil-num=5 en-affil=Department of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Anatomy, College of Medicine, Dongguk University kn-affil= affil-num=7 en-affil=Department of Biomedical Laboratory Science, Dong-Eui Institute of Technology kn-affil= en-keyword=metabolic dysfunction-associated steatohepatitis kn-keyword=metabolic dysfunction-associated steatohepatitis en-keyword=Distylium racemosum kn-keyword=Distylium racemosum en-keyword=ethyl acetate fraction kn-keyword=ethyl acetate fraction en-keyword=extract kn-keyword=extract END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=8 article-no= start-page=1621 end-page=1630 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Percutaneous cryoablation versus robot-assisted partial nephrectomy for small renal cell carcinoma: a retrospective cost analysis at Japanese single-institution en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: No direct cost comparison has been conducted between percutaneous cryoablation (PCA) and robot-assisted partial nephrectomy (RAPN) for clinical T1a renal cell carcinoma (RCC) in Japan. This study aimed to compare their costs.
Methods: We retrospectively analyzed data from 212 PCAs (including 155 with transcatheter arterial embolization) and 119 RAPN cases performed between December 2017 and May 2022.
Results: PCA patients were older with higher American Society of Anesthesiologists scores, Charlson Comorbidity Index, and history of previous RCC treatment, cardiovascular disease, and antithrombotic drug use than RAPN patients. PCA was associated with a significantly shorter procedure time and hospitalization duration with fewer major complications than those associated with RAPN. While PCA incurred a slightly lower total cost (1,123,000 vs. 1,155,000 yen), it had a significantly higher procedural cost (739,000 vs. 693,000 yen) and markedly worse total (? 93,000 vs. 249,000 yen) and procedural income-expenditure balance (? 189,000 vs. 231,000 yen) than those of RAPN. After statistical adjustment, PCA demonstrated significantly higher total (difference: 114,000 yen) and procedural costs (difference: 72,000 yen), alongside significantly worse total (difference: ? 358,000 yen) and procedural income-expenditure balances (difference: ? 439,000 yen). The incremental cost-effectiveness ratio was more favorable for PCA than for RAPN.
Conclusion: For high- risk patients, PCA demonstrated a safer option with shorter hospitalization duration than those of RAPN. Although PCA was more cost-effective, its higher procedural cost and unfavorable income-expenditure balance require careful evaluation, especially for large tumors that require three or more needles. en-copyright= kn-copyright= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GobaraHideo en-aut-sei=Gobara en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UmakoshiNoriyuki en-aut-sei=Umakoshi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawabataTakahiro en-aut-sei=Kawabata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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= 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 Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Medical Informatics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Renal cancer kn-keyword=Renal cancer en-keyword=Cryoablation kn-keyword=Cryoablation en-keyword=Robot-assisted partial nephrectomy kn-keyword=Robot-assisted partial nephrectomy en-keyword=Cost kn-keyword=Cost en-keyword=Cost effectiveness kn-keyword=Cost effectiveness END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=27163 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Eosinophils as a predictive marker of treatment-related adverse events in mRCC patients treated with first-line immune-checkpoint inhibitor combination therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade???3 TRAEs in mRCC patients undergoing ICI combination therapy. In this retrospective analysis across 21 hospitals in Japan, we examined 180 patients treated with ICI/ICI therapy and 216 patients treated with ICI/tyrosine kinase inhibitor (TKI) therapy. Grade???3 TRAEs occurred in 39.4% and 31.9% of patients in the ICI/ICI and ICI/TKI groups, respectively. An elevated eosinophil proportion of???2.0% (odds ratio [OR]: 2.36; 95% CI [confidence interval] 1.23?4.54, p?=?0.01) and a low neutrophil/eosinophil ratio (NER) of???40.0 (OR: 2.78, 95% CI 1.39?5.53, p?=?0.004) were significant predictors of severe TRAEs in the ICI/ICI group. However, no significant associations were found in the ICI/TKI group. These findings may help identify patients who suffer from grade???3 TRAEs and help determine individualized treatment strategies in patients with mRCC. 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=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KomuraKazumasa en-aut-sei=Komura en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujinoTakuya en-aut-sei=Tsujino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NukayaTakuhisa en-aut-sei=Nukaya en-aut-mei=Takuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InokiLan en-aut-sei=Inoki en-aut-mei=Lan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ToyodaShingo en-aut-sei=Toyoda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HashimotoTakeshi en-aut-sei=Hashimoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HirasawaYosuke en-aut-sei=Hirasawa en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 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=17 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=18 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=19 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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=22 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=23 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=24 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=25 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=26 ORCID= en-aut-name=KuroseKyohei en-aut-sei=Kurose en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KimuraTakahiro en-aut-sei=Kimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=AzumaHaruhito en-aut-sei=Azuma en-aut-mei=Haruhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ShirokiRyoichi en-aut-sei=Shiroki en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=FujitaKazutoshi en-aut-sei=Fujita en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=OhnoYoshio en-aut-sei=Ohno en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 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=33 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, The Jikei University School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=8 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=9 en-affil=Department of Urology, Fujita Health University School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Fujita Health University School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=14 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=24 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=25 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=27 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=28 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=29 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=30 en-affil=Department of Urology, Fujita Health University School of Medicine kn-affil= affil-num=31 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=32 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=33 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Renal cell carcinoma kn-keyword=Renal cell carcinoma en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor en-keyword=ICI kn-keyword=ICI en-keyword=Eosinophil kn-keyword=Eosinophil en-keyword=Immune-related adverse event kn-keyword=Immune-related adverse event en-keyword=Treatment-related adverse event kn-keyword=Treatment-related adverse event END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue=13 article-no= start-page=e172988 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250513 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=LAG3 regulates antibody responses in a murine model of kidney transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lymphocyte activation gene 3 (LAG3) is a coinhibitory receptor expressed by various immune cells. Although the immunomodulatory potential of LAG3 is being explored in cancer and autoimmunity, there is no information on its role after organ transplantation. Our study investigated the functions of LAG3 in a mouse model of renal allograft rejection. LAG3?/? recipients rapidly rejected MHC-mismatched renal allografts that were spontaneously accepted by WT recipients, with graft histology characteristic of antibody-mediated rejection. Depletion of recipient B cells but not CD8+ T cells significantly extended kidney allograft survival in LAG3?/? recipients. Treatment of WT recipients with an antagonistic LAG3 antibody enhanced anti-donor immune responses and induced kidney damage associated with chronic rejection. The studies of conditional LAG3?/? recipients and mixed bone marrow chimeras demonstrated that LAG3 expression on either T or B cells is sufficient to regulate anti-donor humoral immunity but not to induce acute allograft rejection. The numbers and proinflammatory functions of graft-infiltrating NK cells were markedly increased in LAG3?/? recipients, suggesting that LAG3 also regulates the effector stage of antibody-mediated rejection. These findings identified LAG3 as a regulator of immune responses to kidney allografts and a potential therapeutic target for antibody-mediated rejection prevention and treatment. en-copyright= kn-copyright= en-aut-name=NicosiaMichael en-aut-sei=Nicosia en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FanRan en-aut-sei=Fan en-aut-mei=Ran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LeeJuyeun en-aut-sei=Lee en-aut-mei=Juyeun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AllGabriella en-aut-sei=All en-aut-mei=Gabriella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GorbachevaVictoria en-aut-sei=Gorbacheva en-aut-mei=Victoria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ValenzuelaJos? I. en-aut-sei=Valenzuela en-aut-mei=Jos? I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoYosuke en-aut-sei=Yamamoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BeaversAshley en-aut-sei=Beavers en-aut-mei=Ashley kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DvorinaNina en-aut-sei=Dvorina en-aut-mei=Nina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=BaldwinWilliam M. en-aut-sei=Baldwin en-aut-mei=William M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ChuluyanEduardo en-aut-sei=Chuluyan en-aut-mei=Eduardo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=GaudetteBrian T. en-aut-sei=Gaudette en-aut-mei=Brian T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FairchildRobert L. en-aut-sei=Fairchild en-aut-mei=Robert L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MinBooki en-aut-sei=Min en-aut-mei=Booki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ValujskikhAnna en-aut-sei=Valujskikh en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=2 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=3 en-affil=Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=4 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=5 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=6 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=7 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=8 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=9 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=10 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=11 en-affil=Universidad de Buenos Aires, Consejo Nacional de Investigaciones Cient?ficas y T?cnicas, Centro de Estudios Farmacol?gicos y Bot?nicos (CEFYBO), Facultad de Medicina kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=14 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=15 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=16 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=5 article-no= start-page=468 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distribution of Fimbrial Genes and Their Association with Virulence and Levofloxacin Resistance/Extended-Spectrum Beta-Lactamase Production in Uropathogenic Escherichia coli en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Urinary tract infection (UTI) is predominantly caused by uropathogenic Escherichia coli (UPEC). Previous studies have reported that the fimbriae of UPEC are involved in virulence and antimicrobial resistance. We aimed to analyze the fimbrial gene profiles of UPEC and investigate the specificity of these expressions in symptomatic UTI, urinary device use, and levofloxacin (LVFX) resistance/extended-spectrum beta-lactamase (ESBL) production. Methods: A total of 120 UPEC strains were isolated by urine culture between 2019 and 2023 at our institution. They were subjected to an antimicrobial susceptibility test and polymerase chain reaction (PCR) to identify 14 fimbrial genes and their association with clinical outcomes or antimicrobial resistance. Results: The prevalence of the papG2 gene was significantly higher in the symptomatic UTI group by multivariate analyses (OR 5.850, 95% CI 1.390?24.70, p = 0.016). The prevalence of the c2395 gene tended to be lower in the symptomatic UTI group with urinary devices (all p < 0.05). In LVFX-resistant UPEC strains from both the asymptomatic bacteriuria (ABU) and the symptomatic UTI group, the expression of the papEF, papG3, c2395, and yadN genes tended to be lower (all p < 0.05). Conclusion: The fimbrial genes of UPEC are associated with virulence and LVFX resistance, suggesting that even UPEC with fewer motility factors may be more likely to ascend the urinary tract in the presence of the urinary devices. These findings may enhance not only the understanding of the virulence of UPEC but also the management of UTI. en-copyright= kn-copyright= en-aut-name=MitsuiMasao en-aut-sei=Mitsui en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaruhashiMai en-aut-sei=Maruhashi en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirakawaHidetada en-aut-sei=Hirakawa en-aut-mei=Hidetada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= 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 Bacteriology, Graduate School of Medicine, Gunma University kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Bacteriology, Graduate School of Medicine, Gunma University kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=fimbriae kn-keyword=fimbriae en-keyword=urinary tract infection kn-keyword=urinary tract infection en-keyword=drug resistance kn-keyword=drug resistance en-keyword=virulence kn-keyword=virulence en-keyword=uropathogenic Escherichia coli kn-keyword=uropathogenic Escherichia coli END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=107 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=Impact of concomitant medications on the oncologic efficacy of systemic therapy in patients with advanced or metastatic urothelial carcinoma: a systematic review and meta-analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Immune checkpoint inhibitors (ICI) and chemotherapy, including antibody-drug conjugates, are widely used for the treatment of patients with advanced unresectable or metastatic urothelial carcinoma (UC). The majority of elderly patients receive concomitant medications to address various comorbidities. We aimed to evaluate the impact of concomitant medications on oncological outcomes in patients with advanced unresectable or metastatic UC treated with systemic therapy.
Material & methods: In August 2024, three datasets were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic UC. The review protocol was registered in PROSPERO (CRD42024547335). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis depending on the heterogeneity.
Results: We identified 16 eligible studies (3 prospective and 13 retrospective) comprising 4,816 patients. Most reported concomitant medications included proton pump inhibitors (PPIs), antibiotics, steroids, and opioids. The use of concomitant PPIs, antibiotics, steroids or opioids during ICI therapy was associated with worsened OS (PPIs: HR: 1.43, 95% CI: 1.31?1.57, p? Conclusions: When treating advanced unresectable or metastatic UC with ICI therapy, we need to pay attention to concomitant medications, such as PPIs and antibiotics to avoid reducing the efficacy of ICI therapy. The mechanism of action of these drugs on ICI efficacy requires further examination. en-copyright= kn-copyright= en-aut-name=TsuboiIchiro en-aut-sei=Tsuboi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PariziMehdi Kardoust en-aut-sei=Parizi en-aut-mei=Mehdi Kardoust kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiszczykMarcin en-aut-sei=Miszczyk en-aut-mei=Marcin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FazekasTam?s en-aut-sei=Fazekas en-aut-mei=Tam?s kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SchulzRobert J en-aut-sei=Schulz en-aut-mei=Robert J kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LaukhtinaEkaterina en-aut-sei=Laukhtina en-aut-mei=Ekaterina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=RajwaPawel en-aut-sei=Rajwa en-aut-mei=Pawel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ObernederKatharina en-aut-sei=Oberneder en-aut-mei=Katharina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ChlostaPiotr en-aut-sei=Chlosta en-aut-mei=Piotr kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KarakiewiczPierre I. en-aut-sei=Karakiewicz en-aut-mei=Pierre I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=5 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=6 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=7 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=8 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=13 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=14 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=15 en-affil=Department of Urology, Medical College, Jagiellonian University kn-affil= affil-num=16 en-affil=Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre kn-affil= affil-num=17 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= en-keyword=Concomitant medications kn-keyword=Concomitant medications en-keyword=Proton pump inhibitors kn-keyword=Proton pump inhibitors en-keyword=Antibiotics kn-keyword=Antibiotics en-keyword=steroids kn-keyword=steroids en-keyword=Opioids kn-keyword=Opioids en-keyword=Histamine type-2 receptor antagonists kn-keyword=Histamine type-2 receptor antagonists en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Urothelial carcinoma kn-keyword=Urothelial carcinoma END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=3 article-no= start-page=258 end-page=263 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Postoperative infections after robotic]assisted radical prostatectomy in a single large institution: Effect of type and duration of prophylactic antibiotic administration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: We evaluated the incidence of and risk factors for postoperative infections after robotic-assisted radical prostatectomy (RARP) according to the type and duration of prophylactic antibiotic administration.
Methods: A total of 1038 patients underwent RARP at our institution from 2010 to 2021; 1026 patients (201 in the cefazolin [CEZ] group and 825 in the ampicillin/sulbactam [ABPC/SBT] group) were analyzed, and 12 who used other antibiotics were excluded. The primary endpoint was the incidence of urinary tract infection (UTI), surgical site infection (SSI), and remote infection (RI). T-tests, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed. Multivariate logistic regression analysis was performed to evaluate the effect of type and duration of prophylactic antibiotic administration.
Results: The incidence of UTI was 2.5% (5/201) in the CEZ group and 3.2% (26/825) in the ABPC/SBT group, with no significant difference between groups (p?=?0.622). The rates of SSI and RI were comparable between groups (p?=?0.680 and 0.906, respectively). Although the duration of antimicrobial therapy was longer in the ABPC/SBT group (p??0.05). Multivariate logistic regression analysis showed that neither the type of antibiotic nor the duration of administration affected the incidence of UTI/SSI/RI.
Conclusion: The risk of postoperative UTI/SSI/RI after RARP did not change with the type and duration of antimicrobial therapy. en-copyright= kn-copyright= en-aut-name=MitsuiMasao en-aut-sei=Mitsui en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagasakiNaoya en-aut-sei=Nagasaki en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SekitoTakanori en-aut-sei=Sekito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=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=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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= 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= en-keyword=cefazolin kn-keyword=cefazolin en-keyword=postoperative infections kn-keyword=postoperative infections en-keyword=prophylactic antibiotics kn-keyword=prophylactic antibiotics en-keyword=prostate kn-keyword=prostate en-keyword=robotic-assisted radical prostatectomy kn-keyword=robotic-assisted radical prostatectomy END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=4 article-no= start-page=48 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Influence of tumor?associated factors on the treatment selection between partial nephrectomy and ablation therapy for small renal tumors (Review) en-subtitle= kn-subtitle= en-abstract= kn-abstract=For small renal tumors, nephron?preserving treatment, including partial nephrectomy or ablation therapy, is recommended. According to major guidelines, ablation therapies are advised for patients who are deemed not suitable to undergo surgery due to an advanced age or the presence of comorbidities. However, compared with surgery, ablation therapy can result in superior safety and functional outcomes. The present review discusses the factors affecting decision?making as regards treatment options for small renal tumors. When determining an appropriate treatment option, tumor locations, as well as the condition and preferences of the patient, are considered. Scoring systems, such as the RENAL Nephrometry Score can assist in guiding treatment decisions. However, surgery may be the preferred approach for tumors near major vessels and collecting systems. For endophytic tumors, partial nephrectomy can be challenging due to the difficulty in visualizing intra?parenchymal tumors during the procedure, whereas ablation therapies may be inferior to partial nephrectomy. Although treatment selection for small renal tumors can be affected by tumor location, partial nephrectomy remains the gold standard for numerous cases. en-copyright= kn-copyright= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueShota en-aut-sei=Inoue en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=small renal mass kn-keyword=small renal mass en-keyword=partial nephrectomy kn-keyword=partial nephrectomy en-keyword=ablation therapy kn-keyword=ablation therapy en-keyword=tumor location kn-keyword=tumor location en-keyword=endophytic tumor kn-keyword=endophytic tumor END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=10 article-no= start-page=1444 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Canine c-kit Novel Mutation Isolated from a Gastrointestinal Stromal Tumor (GIST) Retains the Ability to Form Dimers but Lacks Autophosphorylation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that develop in the gastrointestinal tract; KIT mutations are present in both canine and human GISTs. In this study, genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) sections of 55 canine GIST cases, and mutation searches were performed for exons 8, 9, and 11. The results revealed novel mutations, A434T and F436S, in exon 8. In contrast to the A434T mutation without functional changes, the F436S mutant retained its dimerization ability, but lost its phosphorylation function and attenuated downstream Akt signaling, which is reflected in wound healing and migration activities. A comparison of the subcellular localization of WT KIT and the F436S mutant revealed no differences. In silico simulations indicated that the F436S mutation alters the structure of the near-membrane region and that its effects may extend to the transmembrane and intracellular domains compared to the WT. F436S is a point mutation that affects the entire molecule because co-mutation with the F436S mutation and the known autophosphorylation mutation reduces the autophosphorylation abilities. en-copyright= kn-copyright= en-aut-name=ShimakawaKei en-aut-sei=Shimakawa en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DogeSo en-aut-sei=Doge en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MichishitaMasaki en-aut-sei=Michishita en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanabeEri en-aut-sei=Tanabe en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TajimaTsuyoshi en-aut-sei=Tajima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiMasato en-aut-sei=Kobayashi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BonkobaraMakoto en-aut-sei=Bonkobara en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=OchiaiKazuhiko en-aut-sei=Ochiai en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaYoshikazu en-aut-sei=Tanaka en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=2 en-affil=Laboratory of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=3 en-affil=Laboratory of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=4 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=5 en-affil=Laboratory of Veterinary Pharmacology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=6 en-affil=Laboratory of Veterinary Reproduction, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=7 en-affil=Laboratory of Veterinary Clinical Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=8 en-affil=Laboratory of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=10 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= en-keyword=autophosphorylation kn-keyword=autophosphorylation en-keyword=canine kn-keyword=canine en-keyword=c-kit kn-keyword=c-kit en-keyword=GIST kn-keyword=GIST en-keyword=KIT kn-keyword=KIT en-keyword=loss-of-function mutation kn-keyword=loss-of-function mutation END start-ver=1.4 cd-journal=joma no-vol=144-145 cd-vols= no-issue= article-no= start-page=109001 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigating the fate of Zirconium-89 labelled antibody in cynomolgus macaques en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Preclinical pharmacokinetic studies of therapeutic antibodies in non-human primates are desired because of the difficulty in extrapolating ADME data from animal models to humans. We evaluated the pharmacokinetics of 89Zr (Zirconium-89) -labelled anti-KLH human IgG and its metabolites to confirm their non-specific/physiological accumulation in healthy cynomolgus macaques. The anti-KLH antibody was used as a negative control, ensuring that the observed distribution reflected general IgG behavior rather than antigen-specific accumulation. This provides a valuable reference for comparing the biodistribution of targeted antibodies.
Methods: Selected IgG was conjugated to desferrioxamine (DFO), labelled with 89Zr, and injected into healthy cynomolgus macaques. PET/CT images at the whole-body level were acquired at different time points, and standard uptake values (SUV) in regions of interest, such as the heart, liver, spleen, kidneys, bone, and muscles, were calculated. The distribution of a shortened antibody variant, 89Zr-labelled Fab, as well as that of [89Zr]Zr-DFO and [89Zr]Zr-oxalate, the expected metabolites of 89Zr- labelled IgG, was also assessed.
Results: After 89Zr-labelled IgG injection, the SUV in the heart, vertebral body, and muscle decreased, in line with the 89Zr concentration decrease in the circulation, whereas radioactivity increased over time in the kidneys and liver. Autoradiography of the renal sections indicated that most of the 89Zr- labelled IgG radioactivity accumulated in the renal cortex. Relatively high accumulation in the kidneys was also observed in 89Zr- labelled Fab-injected macaques, and renal autoradiographs of these animals showed that the renal cortex was the preferred accumulation site. However, [89Zr]Zr-DFO was rapidly excreted into the urine, whereas [89Zr]Zr-oxalate was highly accumulated in the epiphysis of the long bones and vertebral body.
Conclusion: In the non-human primate cynomolgus macaque, 89Zr- labelled IgG accumulated in the kidneys and the liver. However, [89Zr]Zr-DFO and 89Zr did not accumulate in these organs. This preclinical pharmacokinetic study performed with human IgG in a non-human primate model using PET is of great significance as it sheds light on the basic fate and distribution of 89Zr- labelled IgG. en-copyright= kn-copyright= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraSadaaki en-aut-sei=Kimura en-aut-mei=Sadaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NodaAkihiro en-aut-sei=Noda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurakamiYoshihiro en-aut-sei=Murakami en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiSosuke en-aut-sei=Miyoshi en-aut-mei=Sosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkehiMasaru en-aut-sei=Akehi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OchiaiKazuhiko en-aut-sei=Ochiai en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=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=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Astellas Pharma Inc. kn-affil= affil-num=3 en-affil=Astellas Pharma Inc. kn-affil= affil-num=4 en-affil=Astellas Pharma Inc. kn-affil= affil-num=5 en-affil=Astellas Pharma Inc. kn-affil= affil-num=6 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=8 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=PET imaging kn-keyword=PET imaging en-keyword=Zirconium-89 kn-keyword=Zirconium-89 en-keyword=Therapeutic antibodies kn-keyword=Therapeutic antibodies en-keyword=Non-human primates kn-keyword=Non-human primates END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=1 end-page=11 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=Evaluating Pericoronary Adipose Tissue?Attenuation to Predict Cardiovascular Events en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Pericoronary adipose tissue attenuation (PCATA) is a novel imaging biomarker of pericoronary inflammation associated with coronary artery disease. Several studies have reported the usefulness of PCATA among people of European ethnicity; however, data are lacking concerning those of Asian ethnicity.
Objectives: This multicenter study aimed to evaluate the effect of PCATA on prognosis in East Asian patients.
Methods: Between August 2011 and December 2016, 2,172 patients underwent clinically indicated coronary computed tomography angiography (CTA) at 4 hospitals in Japan. Among them, 1,270 patients were analyzed. PCATA was evaluated using coronary CTA to measure pericoronary adipose tissue density surrounding the 3 major coronary arteries. The outcomes were composite cardiovascular events, including cardiovascular death and acute coronary syndrome; 33 cardiovascular events observed during a median follow-up of 6.0 years (Q1-Q3: 3.6-8.2 years).
Results: Right coronary artery (RCA)-PCATA was significantly higher in patients with cardiovascular events than in those without (?63.7 } 8.9 HU vs ?67.4 } 9.1 HU, respectively; P = 0.021). High RCA-PCATA was significantly associated with cardiovascular events in a model that included the Hisayama risk score and adverse coronary CTA findings (HR: 1.55; 95% CI: 1.07-2.24; P = 0.019).
Conclusions: High RCA-PCATA showed significant association with future cardiovascular events after adjusting conventional risk factors and adverse coronary CTA findings in East Asian patients who underwent clinically indicated coronary CTA. en-copyright= kn-copyright= en-aut-name=NishiharaTakahiro en-aut-sei=Nishihara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=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=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukeSoichiro en-aut-sei=Fuke en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SeiyamaKousuke en-aut-sei=Seiyama en-aut-mei=Kousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DoiMasayuki en-aut-sei=Doi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MikiTakashi en-aut-sei=Miki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Center kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=6 en-affil=Department of Cardiology, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Cardiology, Kagawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=acute coronary syndrome(s) kn-keyword=acute coronary syndrome(s) en-keyword=coronary computed tomography angiography kn-keyword=coronary computed tomography angiography en-keyword=high-risk plaque kn-keyword=high-risk plaque en-keyword=obstructive stenosis kn-keyword=obstructive stenosis en-keyword=pericoronary adipose tissue attenuation kn-keyword=pericoronary adipose tissue attenuation END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=6 article-no= start-page=1711 end-page=1720 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=Dotinurad Treatment for Patients With Hyperuricemia Complicating CKD en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: The management of hyperuricemia is important to reduce cardiovascular risk and the progression of renal injury in chronic kidney disease (CKD). This study aimed to assess the efficacy and safety of dotinurad, a novel urate transporter-1 inhibitor, in patients with hyperuricemia and CKD.
Methods: In a nonrandomized, parallel interventional study, patients were grouped based on their estimated glomerular filtration rate (eGFR) at baseline. The starting dotinurad dose was 0.5 mg/d and titrated to a final dose of 2 mg/d to 4 mg/d. The primary end point was the noninferiority of the change in serum uric acid (UA) levels between the G1/G2 and G3/G4 groups at week 24. The main secondary end points were changes in eGFR and UA clearance-to-creatinine clearance ratio (CUA/CCr). Reported adverse events were also investigated.
Results: Ninety-eight patients continued the dose titration. The mean percentage reduction in serum UA level at week 24 were 47.2% and 42.8% for the G1/G2 and G3/G4 groups, respectively; the between-group difference was ?4.3% (95% confidence interval [CI], ?9.5% to 0.9%, noninferiority P = 0.0321), validating the noninferiority of treatment in the G3/G4 group to the G1/G2 group. eGFR tended to increase slightly through to week 24, suggesting that spontaneous eGFR decline was counteracted. Mean CUA/CCr generally increased over time from week 4 to week 24. No new safety issues of particular concern were identified; and there were no marked changes in urinary pH.
Conclusion: Dotinurad therapy may be well-tolerated in patients with hyperuricemia and may have efficacy comparable with existing standard treatment in patients with CKD stages G3/G4. Randomized controlled trials in larger patient groups are needed. en-copyright= kn-copyright= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NunoueTomokazu en-aut-sei=Nunoue en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItabashiNaoki en-aut-sei=Itabashi en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatayamaAkihiro en-aut-sei=Katayama en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraAkihiko en-aut-sei=Nakamura en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhbayashiHiroyuki en-aut-sei=Ohbayashi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=WatanabeKyoko en-aut-sei=Watanabe en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaruyamaKeisuke en-aut-sei=Maruyama en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HosoyaTakeshi en-aut-sei=Hosoya en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkadaShinichi en-aut-sei=Okada en-aut-mei=Shinichi 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= 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=Nunoue Clinic kn-affil= affil-num=3 en-affil=Itabashi Diabetes and Dermatology Medical Clinic kn-affil= affil-num=4 en-affil=NHO Okayama Medical Center kn-affil= affil-num=5 en-affil=Osafune Clinic kn-affil= affil-num=6 en-affil=Tohno Chuo Clinic 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=Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Okayama Saiseikai Outpatient Center Hospital kn-affil= affil-num=10 en-affil=Hosoya Clinic kn-affil= affil-num=11 en-affil=Okada Medical Clinic 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= en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=dotinurad kn-keyword=dotinurad en-keyword=efficacy kn-keyword=efficacy en-keyword=hyperuricemia kn-keyword=hyperuricemia en-keyword=safety kn-keyword=safety en-keyword=serum uric acid kn-keyword=serum uric acid END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=15 article-no= start-page=7275 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acquired Radioresistance Through Adaptive Evolution with Gamma Radiation as Selection Pressure: Increased Expression and Induction of Anti-Stress Genes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Elucidating the mechanisms of radioresistance in highly radiotolerant organisms can provide valuable insights into the adaptation and evolution of organisms. However, research has been limited on many naturally occurring radioresistant organisms due to a lack of information regarding their genetic and biochemical characteristics and the difficulty of handling them experimentally. To address this, we conducted an experiment on adaptive evolution using gamma radiation as the selection pressure to generate evolved Escherichia coli with gamma radiation resistance approximately one order of magnitude greater than that of wild-type E. coli. Gene expressions in all wild-type and evolved radioresistant E. coli in the presence or absence of gamma irradiation were analyzed and compared using RNA sequencing. Under steady-state conditions, the genes involved in survival, cell recovery, DNA repair, and response following stress exposure were upregulated in evolved E. coli compared with those in wild-type E. coli. Furthermore, the evolved E. coli induced these genes more efficiently following gamma irradiation and greater DNA repair activity than that in the wild-type E. coli. Our results indicate that an increased steady-state expression of various anti-stress genes, including DNA repair-related genes, and their highly efficient induction under irradiation are responsible for the remarkable radioresistance of evolved E. coli. en-copyright= kn-copyright= en-aut-name=SaitoTakeshi en-aut-sei=Saito en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeratoHiroaki en-aut-sei=Terato en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Division of Radiation Life Science, Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=2 en-affil=Department of Radiation Research, Advanced Science Research Center, Okayama University kn-affil= en-keyword=radioresistant bacteria kn-keyword=radioresistant bacteria en-keyword=Escherichia coli kn-keyword=Escherichia coli en-keyword=adaptive evolution kn-keyword=adaptive evolution en-keyword=gene expression changes kn-keyword=gene expression changes en-keyword=anti-stress genes kn-keyword=anti-stress genes en-keyword=DNA repair kn-keyword=DNA repair en-keyword=cell recovery kn-keyword=cell recovery END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=14 article-no= start-page=e2024GL114146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Unraveling the Complex Features of the Seismic Scatterers in the Mid]Lower Mantle Through Phase Transition of (Al, H)]Bearing Stishovite en-subtitle= kn-subtitle= en-abstract= kn-abstract=Small-scale scatterers observed in the mid-lower mantle beneath the subduction zones are thought to result from the phase transition of stishovite within subducted oceanic crusts. Here we investigate the phase transition of (Al, H)-bearing stishovite with four compositions at simultaneously high P-T conditions combining Raman spectroscopy and X-ray diffraction. These experimental results reveal that the incorporation of 0.01 a.p.f.u Al into stishovite with H/Al ratio of ?1/3 lowers the transition pressure by 6.7(3) GPa. However, the Clapeyron slope of this transition is nearly unaffected by changes in the Al content and has a value of 12.2?12.5(3) MPa/K. According to our results, Al content variation ranging from 0 to 0.07 a.p.f.u in SiO2 can reasonably explain the depth distribution from 800 to 1,900 km of the seismic scatterers observed in the circum-Pacific region. These results deepen our understanding on the complex features of mid-lower mantle seismic scatterers and corresponding dynamic processes. en-copyright= kn-copyright= en-aut-name=YuYingxin en-aut-sei=Yu en-aut-mei=Yingxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhangYouyue en-aut-sei=Zhang en-aut-mei=Youyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiLuo en-aut-sei=Li en-aut-mei=Luo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhangXinyue en-aut-sei=Zhang en-aut-mei=Xinyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangDenglei en-aut-sei=Wang en-aut-mei=Denglei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaoZhu en-aut-sei=Mao en-aut-mei=Zhu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SunNingyu en-aut-sei=Sun en-aut-mei=Ningyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZhangYanyao en-aut-sei=Zhang en-aut-mei=Yanyao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LiXinyang en-aut-sei=Li en-aut-mei=Xinyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LiWancai en-aut-sei=Li en-aut-mei=Wancai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SpezialeSergio en-aut-sei=Speziale en-aut-mei=Sergio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ZhangDongzhou en-aut-sei=Zhang en-aut-mei=Dongzhou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=LinJung]Fu en-aut-sei=Lin en-aut-mei=Jung]Fu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YoshinoTakashi en-aut-sei=Yoshino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=4 en-affil=Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=5 en-affil=Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=6 en-affil=Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=7 en-affil=Deep Space Exploration Laboratory, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=8 en-affil=Earth and Planetary Sciences, Stanford University kn-affil= affil-num=9 en-affil=State Key Laboratory of High Pressure and Superhard Materials, College of Physics, Jilin University kn-affil= affil-num=10 en-affil=CAS Key Laboratory of Crust]Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=11 en-affil=GFZ German Research Centre for Geosciences kn-affil= affil-num=12 en-affil=GeoSoilEnviroCARS, University of Chicago kn-affil= affil-num=13 en-affil=Department of Earth and Planetary Sciences, Jackson School of Geosciences, The University of Texas at Austin kn-affil= affil-num=14 en-affil=Institute for Planetary Materials, Okayama University kn-affil= en-keyword=(Al, H)-bearing stishovite kn-keyword=(Al, H)-bearing stishovite en-keyword=phase transition kn-keyword=phase transition en-keyword=mid-lower mantle kn-keyword=mid-lower mantle en-keyword=small-scale seismic scatterers kn-keyword=small-scale seismic scatterers END start-ver=1.4 cd-journal=joma no-vol=104 cd-vols= no-issue=3 article-no= start-page=104810 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=An ultra-simplified protocol for PCR template preparation from both unsporulated and sporulated Eimeria oocysts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Molecular biological techniques have enabled the accurate identification of the avian Eimeria parasite, however, the preparation of PCR template remains a bottleneck due to contaminants from feces and the robust oocyst's wall resistant to chemical and mechanical force. Generally, the preparation of PCR template involves three main steps: (1) pretreatment of oocysts; (2) disruption of oocysts; and (3) purification of genomic DNA. We prepared PCR templates from both unsporulated and sporulated E. tenella oocysts using various protocols, followed by species-specific PCR to define the limit of detection. Our data revealed that whereas neither pretreatment of oocysts with sodium hypochlorite nor purification of genomic DNA with commercial kits improved the limit of detection of PCR, disruption of oocysts was a critical step in the preparation of PCR templates. The most sensitive PCR assay was achieved with the template prepared by disrupting oocysts suspended in distilled water, followed by bead-beating and heating at 99‹C for 5 min, which detected 0.16 oocysts per PCR. This ultra-simplified protocol for preparation of PCR template, which does not require expensive reagents or equipment, will significantly enhance the sensitive and efficient molecular identification of Eimeria. It will improve our understanding of the prevalence of this parasite at the species level and contribute to the development of techniques for the control in the field. en-copyright= kn-copyright= en-aut-name=TakanoAruto en-aut-sei=Takano en-aut-mei=Aruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UmaliDennis V. en-aut-sei=Umali en-aut-mei=Dennis V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WardhanaApril H. en-aut-sei=Wardhana en-aut-mei=April H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SawitriDyah H. en-aut-sei=Sawitri en-aut-mei=Dyah H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TeramotoIsao en-aut-sei=Teramoto en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HatabuToshimitsu en-aut-sei=Hatabu en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KidoYasutoshi en-aut-sei=Kido en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanekoAkira en-aut-sei=Kaneko en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SasaiKazumi en-aut-sei=Sasai en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatohHiromitsu en-aut-sei=Katoh en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsubayashiMakoto en-aut-sei=Matsubayashi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Departments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan University kn-affil= affil-num=2 en-affil=Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of the Philippines Los Ba?os, College kn-affil= affil-num=3 en-affil=Research Center for Veterinary Science, National Research and Innovation Agency kn-affil= affil-num=4 en-affil=Research Center for Veterinary Science, National Research and Innovation Agency kn-affil= affil-num=5 en-affil=Departments of Virology and Parasitology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=6 en-affil=Laboratory of Animal Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Departments of Virology and Parasitology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=8 en-affil=Departments of Virology and Parasitology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=9 en-affil=Departments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan University kn-affil= affil-num=10 en-affil=Departments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan University kn-affil= affil-num=11 en-affil=Departments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan University kn-affil= en-keyword=Coccidian parasite kn-keyword=Coccidian parasite en-keyword=Eimeria tenella kn-keyword=Eimeria tenella en-keyword=Extraction kn-keyword=Extraction en-keyword=Molecular identification kn-keyword=Molecular identification en-keyword=Oocyst kn-keyword=Oocyst END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=7 article-no= start-page=koaf142 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pancentromere analysis of Allium species reveals diverse centromere positions in onion and gigantic centromeres in garlic en-subtitle= kn-subtitle= en-abstract= kn-abstract=In eukaryotes, centromeres interact with the kinetochore for distribution of genetic information in cell division, yet their sequence and size are diverse among species. However, their position on chromosomes is considered to be conserved within a species. In this study, we analyzed the centromeres of 3 Allium species, namely, Welsh onion (Allium fistulosum), onion (Allium cepa), and garlic (Allium sativum) via pancentromere analysis and repetitive sequence analysis of centromeres and their neighborhoods and revealed their mobility, sequence organization, and size. Among the 3 species, Welsh onion and garlic had stable centromeres, but the onion centromere appeared to be polymorphic and frequently differed in position by up to 28.0?Mb among cultivars and between multiple individuals of the same cultivar. This mobility was stabilized by hybridization with Welsh onions. Furthermore, these 3 species have very different centromere sequence organization, including differences in the existence and maturity of centromeric satellites, and differences in centromere size, with Welsh onion having a centromere of 1.9?Mb, and garlic having a centromere of ?10.6?Mb, the largest of any organism with monocentric chromosomes analyzed to date. Our pancentromere analysis of these Allium species reveals the variation in sequence organization, size, and position of this important chromosomal region. en-copyright= kn-copyright= en-aut-name=NagakiKiyotaka en-aut-sei=Nagaki en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=AkagiTakashi en-aut-sei=Akagi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaKeisuke en-aut-sei=Tanaka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHisato en-aut-sei=Kobayashi en-aut-mei=Hisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, 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 Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= affil-num=5 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=10 article-no= start-page=2401783 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biocompatibility of Water-Dispersible Pristine Graphene and Graphene Oxide Using a Close-to-Human Animal Model: A Pilot Study on Swine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Graphene-based materials (GBMs) are of considerable interest for biomedical applications, and the pilot study on the toxicological and immunological impact of pristine graphene (GR) and graphene oxide (GO) using swine as a close-to-human provides valuable insights. First, ex vivo experiments are conducted on swine blood cells, then GBMs are injected intraperitoneally (i.p.) into swine. Hematological and biochemical analyses at various intervals indicate that neither GO nor GR cause systemic inflammation, pro-coagulant responses, or renal or hepatic dysfunction. Importantly, no systemic toxicity is observed. Analysis of a panel of 84 immune-related genes shows minimal impact of GO and GR. The animals are sacrificed 21 days post-injection, and transient absorption imaging and Raman mapping show the presence of GO and GR in the mesentery only. Histological evaluation reveals no signs of alterations in other organs. Thus, clusters of both materials are detected in the mesentery, and GO aggregates are surrounded only by macrophages with the formation of granulomas. In contrast, modest local reactions are observed around the GR clusters. Overall, these results reveal that i.p. injection of GBMs resulted in a modest local tissue reaction without systemic toxicity. This study, performed in swine, provides essential guidance for future biomedical applications of graphene. en-copyright= kn-copyright= en-aut-name=NicolussiPaola en-aut-sei=Nicolussi en-aut-mei=Paola kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PiloGiovannantonio en-aut-sei=Pilo en-aut-mei=Giovannantonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CanceddaMaria Giovanna en-aut-sei=Cancedda en-aut-mei=Maria Giovanna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PengGuotao en-aut-sei=Peng en-aut-mei=Guotao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChauNgoc Do Quyen en-aut-sei=Chau en-aut-mei=Ngoc Do Quyen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=De la CadenaAlejandro en-aut-sei=De la Cadena en-aut-mei=Alejandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=VannaRenzo en-aut-sei=Vanna en-aut-mei=Renzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SamadYarjan Abdul en-aut-sei=Samad en-aut-mei=Yarjan Abdul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AhmedTanweer en-aut-sei=Ahmed en-aut-mei=Tanweer kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MarcellinoJeremia en-aut-sei=Marcellino en-aut-mei=Jeremia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TeddeGiuseppe en-aut-sei=Tedde en-aut-mei=Giuseppe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GiroLinda en-aut-sei=Giro en-aut-mei=Linda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YlmazerAcelya en-aut-sei=Ylmazer en-aut-mei=Acelya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=LoiFederica en-aut-sei=Loi en-aut-mei=Federica kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=CartaGavina en-aut-sei=Carta en-aut-mei=Gavina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SecchiLoredana en-aut-sei=Secchi en-aut-mei=Loredana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Dei GiudiciSilvia en-aut-sei=Dei Giudici en-aut-mei=Silvia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MacciocuSimona en-aut-sei=Macciocu en-aut-mei=Simona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=PolliDario en-aut-sei=Polli en-aut-mei=Dario kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 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=20 ORCID= en-aut-name=LigiosCiriaco en-aut-sei=Ligios en-aut-mei=Ciriaco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=CerulloGiulio en-aut-sei=Cerullo en-aut-mei=Giulio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FerrariAndrea en-aut-sei=Ferrari en-aut-mei=Andrea kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 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=24 ORCID= en-aut-name=FadeelBengt en-aut-sei=Fadeel en-aut-mei=Bengt kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FranzoniGiulia en-aut-sei=Franzoni en-aut-mei=Giulia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=DeloguLucia Gemma en-aut-sei=Delogu en-aut-mei=Lucia Gemma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=2 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=3 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=4 en-affil=Institute of Environmental Medicine, Karolinska Institutet kn-affil= affil-num=5 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry kn-affil= affil-num=6 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=7 en-affil=Istituto di Fotonica e Nanotecnologie ? CNR kn-affil= affil-num=8 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=9 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=10 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=11 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=12 en-affil=ImmuneNano Laboratory, Department of Biomedical Sciences kn-affil= affil-num=13 en-affil=Department of Biomedical Engineering, Ankara University kn-affil= affil-num=14 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=15 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=16 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=17 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=18 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=19 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=20 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=21 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=22 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=23 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=24 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry kn-affil= affil-num=25 en-affil=Institute of Environmental Medicine, Karolinska Institutet kn-affil= affil-num=26 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=27 en-affil=ImmuneNano Laboratory, Department of Biomedical Sciences kn-affil= en-keyword=2D materials kn-keyword=2D materials en-keyword=biocompatibility kn-keyword=biocompatibility en-keyword=immune system kn-keyword=immune system en-keyword=porcine model kn-keyword=porcine model en-keyword=toxicity kn-keyword=toxicity END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=4 article-no= start-page=263 end-page=272 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240607 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Light-Responsive and Antibacterial Graphenic Materials as a Holistic Approach to Tissue Engineering en-subtitle= kn-subtitle= en-abstract= kn-abstract=While the continuous development of advanced bioprinting technologies is under fervent study, enhancing the regenerative potential of hydrogel-based constructs using external stimuli for wound dressing has yet to be tackled. Fibroblasts play a significant role in wound healing and tissue implants at different stages, including extracellular matrix production, collagen synthesis, and wound and tissue remodeling. This study explores the synergistic interplay between photothermal activity and nanomaterial-mediated cell proliferation. The use of different graphene-based materials (GBM) in the development of photoactive bioinks is investigated. In particular, we report the creation of a skin-inspired dressing for wound healing and regenerative medicine. Three distinct GBM, namely, graphene oxide (GO), reduced graphene oxide (rGO), and graphene platelets (GP), were rigorously characterized, and their photothermal capabilities were elucidated. Our investigations revealed that rGO exhibited the highest photothermal efficiency and antibacterial properties when irradiated, even at a concentration as low as 0.05 mg/mL, without compromising human fibroblast viability. Alginate-based bioinks alongside human fibroblasts were employed for the bioprinting with rGO. The scaffold did not affect the survival of fibroblasts for 3 days after bioprinting, as cell viability was not affected. Remarkably, the inclusion of rGO did not compromise the printability of the hydrogel, ensuring the successful fabrication of complex constructs. Furthermore, the presence of rGO in the final scaffold continued to provide the benefits of photothermal antimicrobial therapy without detrimentally affecting fibroblast growth. This outcome underscores the potential of rGO-enhanced hydrogels in tissue engineering and regenerative medicine applications. Our findings hold promise for developing game-changer strategies in 4D bioprinting to create smart and functional tissue constructs with high fibroblast proliferation and promising therapeutic capabilities in drug delivery and bactericidal skin-inspired dressings. en-copyright= kn-copyright= en-aut-name=FerrerasAndrea en-aut-sei=Ferreras en-aut-mei=Andrea kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatesanzAna en-aut-sei=Matesanz en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MendizabalJabier en-aut-sei=Mendizabal en-aut-mei=Jabier kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArtolaKoldo en-aut-sei=Artola en-aut-mei=Koldo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=AcedoPablo en-aut-sei=Acedo en-aut-mei=Pablo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=JorcanoJos? L. en-aut-sei=Jorcano en-aut-mei=Jos? L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=RuizAmalia en-aut-sei=Ruiz en-aut-mei=Amalia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ReinaGiacomo en-aut-sei=Reina en-aut-mei=Giacomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Mart?nCristina en-aut-sei=Mart?n en-aut-mei=Cristina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Bioengineering, Universidad Carlos III de Madrid kn-affil= affil-num=2 en-affil=Department of Electronic Technology, Universidad Carlos III de Madrid kn-affil= affil-num=3 en-affil=Domotek ingenier?a prototipado y formaci?n S.L. kn-affil= affil-num=4 en-affil=Domotek ingenier?a prototipado y formaci?n S.L. kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Department of Electronic Technology, Universidad Carlos III de Madrid kn-affil= affil-num=7 en-affil=Department of Bioengineering, Universidad Carlos III de Madrid kn-affil= affil-num=8 en-affil=Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford kn-affil= affil-num=9 en-affil=Empa Swiss Federal Laboratories for Materials Science and Technology kn-affil= affil-num=10 en-affil=Department of Bioengineering, Universidad Carlos III de Madrid kn-affil= en-keyword=photothermal therapy kn-keyword=photothermal therapy en-keyword=graphene derivatives kn-keyword=graphene derivatives en-keyword=4D bioprinting kn-keyword=4D bioprinting en-keyword=alginate kn-keyword=alginate en-keyword=tissue engineering kn-keyword=tissue engineering END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=12 article-no= start-page=4932 end-page=4951 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The leucine-rich repeat receptor kinase QSK1 regulates PRR-RBOHD complexes targeted by the bacterial effector HopF2Pto en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plants detect pathogens using cell-surface pattern recognition receptors (PRRs) such as ELONGATION Factor-TU (EF-TU) RECEPTOR (EFR) and FLAGELLIN SENSING 2 (FLS2), which recognize bacterial EF-Tu and flagellin, respectively. These PRRs belong to the leucine-rich repeat receptor kinase (LRR-RK) family and activate the production of reactive oxygen species via the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD). The PRR-RBOHD complex is tightly regulated to prevent unwarranted or exaggerated immune responses. However, certain pathogen effectors can subvert these regulatory mechanisms, thereby suppressing plant immunity. To elucidate the intricate dynamics of the PRR-RBOHD complex, we conducted a comparative coimmunoprecipitation analysis using EFR, FLS2, and RBOHD in Arabidopsis thaliana. We identified QIAN SHOU KINASE 1 (QSK1), an LRR-RK, as a PRR-RBOHD complex-associated protein. QSK1 downregulated FLS2 and EFR abundance, functioning as a negative regulator of PRR-triggered immunity (PTI). QSK1 was targeted by the bacterial effector HopF2Pto, a mono-ADP ribosyltransferase, reducing FLS2 and EFR levels through both transcriptional and transcription-independent pathways, thereby inhibiting PTI. Furthermore, HopF2Pto transcriptionally downregulated PROSCOOP genes encoding important stress-regulated phytocytokines and their receptor MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2. Importantly, HopF2Pto requires QSK1 for its accumulation and virulence functions within plants. In summary, our results provide insights into the mechanism by which HopF2Pto employs QSK1 to desensitize plants to pathogen attack. en-copyright= kn-copyright= en-aut-name=GotoYukihisa en-aut-sei=Goto en-aut-mei=Yukihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KadotaYasuhiro en-aut-sei=Kadota en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MbengueMalick en-aut-sei=Mbengue en-aut-mei=Malick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LewisJennifer D en-aut-sei=Lewis en-aut-mei=Jennifer D kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MakiNoriko en-aut-sei=Maki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NgouBruno Pok Man en-aut-sei=Ngou en-aut-mei=Bruno Pok Man kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SklenarJan en-aut-sei=Sklenar en-aut-mei=Jan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DerbyshirePaul en-aut-sei=Derbyshire en-aut-mei=Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShibataArisa en-aut-sei=Shibata en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchihashiYasunori en-aut-sei=Ichihashi en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GuttmanDavid S en-aut-sei=Guttman en-aut-mei=David S kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakagamiHirofumi en-aut-sei=Nakagami en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SuzukiTakamasa en-aut-sei=Suzuki en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MenkeFrank L H en-aut-sei=Menke en-aut-mei=Frank L H kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=RobatzekSilke en-aut-sei=Robatzek en-aut-mei=Silke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DesveauxDarrell en-aut-sei=Desveaux en-aut-mei=Darrell kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ZipfelCyril en-aut-sei=Zipfel en-aut-mei=Cyril kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShirasuKen en-aut-sei=Shirasu en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=2 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=3 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=4 en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=7 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=8 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=9 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=10 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=11 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=12 en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto kn-affil= affil-num=13 en-affil=Plant Proteomics Research Unit, RIKEN CSRS kn-affil= affil-num=14 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=15 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=16 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=17 en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto kn-affil= affil-num=18 en-affil=Institute of Plant and Microbial Biology, Zurich-Basel Plant Science Center, University of Zurich kn-affil= affil-num=19 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electrochemical Generation of Sulfonamidyl Radicals via Anodic Oxidation of Hydrogen Bonding Complexes: Applications to Electrosynthesis of Benzosultams en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amidyl radicals and sulfonamidyl radicals are widely used in the field of organic synthesis. In particular, the electrochemical oxidation of amides in the presence of bases is one of the most practical methods for generating amidyl radicals. However, it is often difficult to observe the gtrueh radical precursor, such as an amide anion and/or a hydrogen bonding complex with an amide and a base. We found that a sulfonamide and Bu4NOAc form a 1:1 hydrogen bonding complex by spectroscopic experiments. Cyclic voltammetry suggested that 1:1 hydrogen bonding complexes should be oxidized predominantly under the optimized conditions to afford a sulfonamidyl radical via the proton-coupled electron transfer (PCET) process by the oxidation of the complex. Thus-generated sulfonamidyl radicals could be used in the electrochemical synthesis of a variety of benzosultams. en-copyright= kn-copyright= en-aut-name=OkumuraYasuyuki en-aut-sei=Okumura en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoEisuke en-aut-sei=Sato en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsudoKoichi en-aut-sei=Mitsudo en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=electrochemical generation kn-keyword=electrochemical generation en-keyword=sulfonamidyl radicals kn-keyword=sulfonamidyl radicals en-keyword=hydrogen bonding complexes kn-keyword=hydrogen bonding complexes en-keyword=anodic oxidation kn-keyword=anodic oxidation en-keyword=proton-coupled electron transfer kn-keyword=proton-coupled electron transfer en-keyword=electrosynthesis kn-keyword=electrosynthesis en-keyword=benzosultams kn-keyword=benzosultams en-keyword=cyclization kn-keyword=cyclization END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page=e88945 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Six-Year Remission With No Relapse After Four-Time Weekly Rituximab Only for Bilateral Ocular Adnexal Follicular Lymphoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Follicular lymphoma mostly takes an indolent course, and thus, observation with watchful waiting is a main therapeutic strategy. Recent long-term studies suggest earlier treatment with rituximab monotherapy may benefit patients by delaying the need for treatment in the later phase of exacerbation. In this study, we reported a patient with bilateral orbital follicular lymphoma who received four-time weekly rituximab monotherapy as an induction therapy only and maintained the remission for 5 years with no treatment. The patient was a 51-year-old woman who developed a right upper orbital mass and was diagnosed with follicular lymphoma grade 1 by the excisional biopsy. Two years later, at the age of 53 years, she developed a left lacrimal gland mass and underwent excision. The pathological diagnosis was follicular lymphoma grade 1. She did not have any other systemic lesions by fluorodeoxyglucose positron emission tomography. At the age of 54 years, she developed a new mass on the nasal side of the right orbit and underwent weekly rituximab monotherapy (375 mg/m2) four times a month, leading to the reduction of the mass in 3 months. Two high uptake sites on the temporal and nasal side of the right superior orbit by fluorodeoxyglucose positron emission tomography disappeared one year later at the age of 55 years. She was followed with no treatment for 6 years until the age of 60 years at the latest visit. In case of a local orbital relapse, local radiotherapy would be the standard, but rituximab monotherapy as an induction therapy only was chosen in the present patient. Rituximab monotherapy in place of local radiotherapy would be a treatment option for orbital follicular lymphoma. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, and Okayama University Hospital 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=Division of Transfusion and Cell Therapy, Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=claustrophobia kn-keyword=claustrophobia en-keyword=extranodal marginal zone b-cell lymphoma mucosa-associated lymphoid tissue (malt) type kn-keyword=extranodal marginal zone b-cell lymphoma mucosa-associated lymphoid tissue (malt) type en-keyword=fluorodeoxyglucose positron emission tomography kn-keyword=fluorodeoxyglucose positron emission tomography en-keyword=follicular lymphoma kn-keyword=follicular lymphoma en-keyword=magnetic resonance imaging kn-keyword=magnetic resonance imaging en-keyword=mucosaassociated lymphoid tissue (malt) lymphoma kn-keyword=mucosaassociated lymphoid tissue (malt) lymphoma en-keyword=ocular adnexa kn-keyword=ocular adnexa en-keyword=orbital mass kn-keyword=orbital mass en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=rituximab kn-keyword=rituximab END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=11 article-no= start-page=uhae248 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A low-cost dpMIG-seq method for elucidating complex inheritance in polysomic crops: a case study in tetraploid blueberry en-subtitle= kn-subtitle= en-abstract= kn-abstract=Next-generation sequencing (NGS) library construction often requires high-quality DNA extraction, precise adjustment of DNA concentration, and restriction enzyme digestion to reduce genome complexity, which results in increased time and cost in sample preparation and processing. To address these challenges, a PCR-based method for rapid NGS library preparation, named dpMIG-seq, has been developed and proven effective for high-throughput genotyping. However, the application of dpMIG-seq has been limited to diploid and polyploid species with disomic inheritance. In this study, we obtained genome-wide single nucleotide polymorphism (SNP) markers for tetraploid blueberry to evaluate genotyping and downstream analysis outcomes. Comparison of genotyping qualities inferred across samples with different DNA concentrations and multiple bioinformatics approaches revealed high accuracy and reproducibility of dpMIG-seq-based genotyping, with Pearson's correlation coefficients between replicates in the range of 0.91 to 0.98. Furthermore, we demonstrated that dpMIG-seq enables accurate genotyping of samples with low DNA concentrations. Subsequently, we applied dpMIG-seq to a tetraploid F1 population to examine the inheritance probability of parental alleles. Pairing configuration analysis supported the random meiotic pairing of homologous chromosomes on a genome-wide level. On the other hand, preferential pairing was observed on chr-11, suggesting that there may be an exception to the random pairing. Genotypic data suggested quadrivalent formation within the population, although the frequency of quadrivalent formation varied by chromosome and cultivar. Collectively, the results confirmed applicability of dpMIG-seq for allele dosage genotyping and are expected to catalyze the adoption of this cost-effective and rapid genotyping technology in polyploid studies. en-copyright= kn-copyright= en-aut-name=NagasakaKyoka en-aut-sei=Nagasaka en-aut-mei=Kyoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraKazusa en-aut-sei=Nishimura en-aut-mei=Kazusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotokiKo en-aut-sei=Motoki en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamagataKeigo en-aut-sei=Yamagata en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiyamaSoichiro en-aut-sei=Nishiyama en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamaneHisayo en-aut-sei=Yamane en-aut-mei=Hisayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaoRyutaro en-aut-sei=Tao en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoRyohei en-aut-sei=Nakano en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakazakiTetsuya en-aut-sei=Nakazaki en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Agriculture, Kyoto 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 Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=6 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=7 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=8 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=9 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=6 article-no= start-page=271 end-page=285 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=Effects of Sediment Microbial Fuel Cells on CH4 and CO2 Emissions from Straw Amended Paddy Soil en-subtitle= kn-subtitle= en-abstract= kn-abstract=Straw returning into paddy soil enhances soil organic matter which usually promotes the emission of greenhouse gases to the atmosphere. The application of sediment microbial fuel cells (SMFCs) to paddy soil activates power-generating microorganisms and enhances organic matter biodegradation. In the present study, rice straw addition in SMFCs was examined to determine its effect on CH4 and CO2 emissions. Columns (height, 25?cm; inner diameter, 9?cm) with four treatments: soil without and with rice straw under SMFC and without SMFC conditions were incubated at 25‹C for 70 days. Anodic potential values at 7?cm depth sediment were kept higher by SMFCs than those without SMFCs. Cumulative CH4 emission was significantly reduced by SMFC with straw amendment (p < 0.05) with no significant effect on CO2 emission. 16S rRNA gene analysis results showed that Firmicutes at the phylum, Closteridiales and Acidobacteriales at order level were dominant on the anode of straw-added SMFC, whereas Methanomicrobiales were in the treatment without SMFC, indicating that a certain group of methanogens were suppressed by SMFC. Our results suggest that the anodic redox environment together with the enrichment of straw-degrading bacteria contributed to a competitive advantage of electrogenesis over methanogenesis in straw-added SMFC system. en-copyright= kn-copyright= en-aut-name=BekeleAdhena Tesfau en-aut-sei=Bekele en-aut-mei=Adhena Tesfau kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaMorihiro en-aut-sei=Maeda en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkaoSatoshi en-aut-sei=Akao en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SomuraHiroaki en-aut-sei=Somura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoChiyu en-aut-sei=Nakano en-aut-mei=Chiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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 Science and Engineering, Doshisha University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Organization for Research Strategy and Development, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=straw kn-keyword=straw en-keyword=methane mitigation kn-keyword=methane mitigation en-keyword=SMFC kn-keyword=SMFC en-keyword=microorganisms kn-keyword=microorganisms en-keyword=current generation kn-keyword=current generation END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=7 article-no= start-page=001430 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250707 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic features of three major diarrhoeagenic Escherichia coli pathotypes in India en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background. Diarrhoea remains a major threat to children in developing nations, with diarrhoeagenic Escherichia coli (DEC) being the primary causative agent. Characterizing prevalent DEC strains is crucial, yet comprehensive genomic analyses of major DEC strains, including enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC) and enterotoxigenic E. coli (ETEC), are lacking in India.
Methods. We sequenced 24 EAEC and 23 EPEC strains from Indian patients with diarrhoea and conducted an extensive database search for DEC human isolates from India. Detailed phylogenetic analyses, virulence gene subtyping and examinations of accessory virulence and antimicrobial resistance (AMR) genes were performed.
Results. The analysed DEC strains included 32 EAEC, 25 EPEC, 32 ETEC and 1 each of the EPEC/ETEC-hybrid and ETEC/EAEC-hybrid pathotypes. These strains were predominantly classified into phylogroups A (35.2%) and B1 (41.8%) and dispersed within these phylogroups without pathotype-specific clustering. One ETEC strain was classified into cryptic clade 1. Subtypes of hallmark virulence genes varied substantially amongst strains in each pathotype, and 31 accessory virulence genes were detected either specifically within certain pathotypes or across multiple pathotypes at varying frequencies, indicating diversification of the virulence gene repertoire within each pathotype. Acquired AMR genes were found in 73.6% of the strains, with frequent identification of AMR genes for aminoglycosides (40.0%), ƒÀ-lactams (64.8%), sulphonamides (49.5%) and trimethoprim (42.9%). Known quinolone-resistant mutations were found in 74.7% of the strains, whereas AMR genes for macrolide (30.8%), phenicol (11.0%) and tetracycline (27.4%) were less frequent.
Conclusions. The diverse virulence potential and trends in AMR gene prevalence amongst major DEC strains in India are highlighted in this study. Continuous monitoring of DEC strain characteristics is essential for the effective control and treatment of DEC infections in India. en-copyright= kn-copyright= en-aut-name=HoshikoYuki en-aut-sei=Hoshiko en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=GhoshDebjani en-aut-sei=Ghosh en-aut-mei=Debjani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaganoDebora Satie en-aut-sei=Nagano en-aut-mei=Debora Satie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhnoAyumu en-aut-sei=Ohno en-aut-mei=Ayumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=OkunoMiki en-aut-sei=Okuno en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoTakeshi en-aut-sei=Yamamoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=OguraYoshitoshi en-aut-sei=Ogura en-aut-mei=Yoshitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=?Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine kn-affil= affil-num=2 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=3 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=4 en-affil=Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=5 en-affil=?Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine kn-affil= affil-num=6 en-affil=Collaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=7 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=?Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine kn-affil= affil-num=9 en-affil=?Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine kn-affil= affil-num=10 en-affil=?Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=11 en-affil=?Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases kn-affil= affil-num=12 en-affil=?Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine kn-affil= en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=diarrhoeagenic Escherichia coli kn-keyword=diarrhoeagenic Escherichia coli en-keyword=genome kn-keyword=genome en-keyword=India kn-keyword=India en-keyword=virulence gene kn-keyword=virulence gene END start-ver=1.4 cd-journal=joma no-vol=93 cd-vols= no-issue=4 article-no= start-page=335 end-page=343 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=Elucidation of Low-temperature Regulated Flavone Synthesis in Dahlia Variabilis and its Effects on Flower Color en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dahlia (Dahlia variabilis) flower colors are diverse and are determined by the accumulation of flavonoids. Cultivars with dark red flowers accumulate more anthocyanins in their petals. Flower color changes such as color fading often occur in some cultivars. In this study, low minimum temperature regulated flower color fading and flavonoid synthesis in dahlia eNesshof were investigated. The pigment contents and expression levels of flavonoid biosynthesis genes were investigated in detail under several growing environments in which color fading occurs. Flavones accumulate more in color-faded orange flowers than in dark red ray florets. The expression analysis of the anthocyanin synthesis pathway genes indicated that the upregulation of flavone synthase (DvFNS) gene expression correlated with the high accumulation of flavones in color-faded petals. DvFNS expression was also detected in young leaves, and the expression level was higher in winter than in summer. Seasonal changes in DvFNS expression in young leaves significantly correlated with color fading in petals. The change in DvFNS expression in young unexpanded leaves of relatively high-sensitive plants was significantly higher than that of low-sensitive plants before and after treatment under inductive conditions. In conclusion, low-temperature-inducible changes in the flavonoid accumulation in petals was suggested to reflect a change in DvFNS expression occurring in the meristem prior to flower bud formation. This temporal DvFNS expression in young unexpanded leaves of eNesshof dahlia could be an insight for the selection and breeding of non-color fading plants. en-copyright= kn-copyright= en-aut-name=K. MuthamiaEdna en-aut-sei=K. Muthamia en-aut-mei=Edna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaitoKoji en-aut-sei=Naito en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaHiromasa en-aut-sei=Okada en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KarasawaYukino en-aut-sei=Karasawa en-aut-mei=Yukino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikumuraTokuyu en-aut-sei=Kikumura en-aut-mei=Tokuyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaraTakuya en-aut-sei=Nara en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamauzuYasunori en-aut-sei=Hamauzu en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MotokiKo en-aut-sei=Motoki en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YasubaKen-ichiro en-aut-sei=Yasuba en-aut-mei=Ken-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshidaYuichi en-aut-sei=Yoshida en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KitamuraYoshikuni en-aut-sei=Kitamura en-aut-mei=Yoshikuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GotoTanjuro en-aut-sei=Goto en-aut-mei=Tanjuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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 Agriculture, Shinshu University kn-affil= affil-num=4 en-affil=Faculty of Agriculture, Shinshu University kn-affil= affil-num=5 en-affil=Faculty of Agriculture, Shinshu University kn-affil= affil-num=6 en-affil=Faculty of Agriculture, Shinshu University kn-affil= affil-num=7 en-affil=Faculty of Agriculture, Shinshu 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 Environmental and Life Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=12 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=anthocyanin kn-keyword=anthocyanin en-keyword=dahlia kn-keyword=dahlia en-keyword=flavone synthase kn-keyword=flavone synthase en-keyword=seasonal color fading kn-keyword=seasonal color fading en-keyword=young unexpanded leaves kn-keyword=young unexpanded leaves END start-ver=1.4 cd-journal=joma no-vol=238 cd-vols= no-issue= article-no= start-page=120296 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=Grafting-through functionalization of graphene oxide with cationic polymers for enhanced adsorption of anionic dyes and viruses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Graphene oxide (GO) is a sheet-like carbon material with abundant oxygen-containing functional groups on its surface. GO has been extensively studied as an adsorbent for heavy metals and organic compounds. However, effective strategies for negatively charged materials have yet to be established. This study aimed to synthesize composites of GO and cationic polymers for the selective adsorption of negatively charged materials; a challenge in this approach is the strong electrostatic interactions between GO and cationic polymers, which can lead to aggregation. This study addresses this issue by employing the grafting-through method. GO was initially modified with allylamine to introduce a polymerizable site, followed by radical polymerization to covalently bond polymers to the GO surface, effectively preventing aggregation. Adsorption experiments demonstrated that the GO-polymer composite selectively adsorbs anionic dye, such as methyl orange. Virus adsorption tests showed significantly enhanced performance compared to pristine GO. These results emphasize the critical role of controlled surface modification and charge manipulation in optimizing the adsorption performance of GO. This study establishes a simple and effective approach for synthesizing GO-cationic polymer composites, contributing to the development of advanced materials for water purification applications. en-copyright= kn-copyright= en-aut-name=KimuraRyota en-aut-sei=Kimura en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= 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=2 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=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=Research Core for Interdisciplinary Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Graphene oxide kn-keyword=Graphene oxide en-keyword=Virus adsorption kn-keyword=Virus adsorption en-keyword=Dye adsorption kn-keyword=Dye adsorption en-keyword=Cationic polymer composites kn-keyword=Cationic polymer composites en-keyword=Adsorbent kn-keyword=Adsorbent en-keyword=Aggregation kn-keyword=Aggregation 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=20250723 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of differences in computed tomography value-electron density/physical density conversion tables on calculate dose in low-density areas en-subtitle= kn-subtitle= en-abstract= kn-abstract=In radiotherapy treatment planning, the extrapolation of computed tomography (CT) values for low-density areas without known materials may differ between CT scanners, resulting in different calculated doses. We evaluated the differences in the percentage depth dose (PDD) calculated using eight CT scanners. Heterogeneous virtual phantoms were created using LN-300 lung and ??900 HU. For the two types of virtual phantoms, the PDD on the central axis was calculated using five energies, two irradiation field sizes, and two calculation algorithms (the anisotropic analytical algorithm and Acuros XB). For the LN-300 lung, the maximum CT value difference between the eight CT scanners was 51 HU for an electron density (ED) of 0.29 and 8.8 HU for an extrapolated ED of 0.05. The LN-300 lung CT values showed little variation in the CT-ED/physical density data among CT scanners. The difference in the point depth for the PDD in the LN-300 lung between the CT scanners was??5%, and the dose difference corresponding to an LN-300 lung CT value difference of?>?20 HU was?>?1% at a field size of 2?~?2 cm2. The study findings suggest that the calculated dose of low-density regions without known materials in the CT-ED conversion table introduces a risk of dose differences between facilities because of the calibration of the CT values, even when the same CT-ED phantom radiation treatment planning and treatment devices are used. en-copyright= kn-copyright= en-aut-name=NomuraMia en-aut-sei=Nomura en-aut-mei=Mia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GotoShunsuke en-aut-sei=Goto en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshiokaMizuki en-aut-sei=Yoshioka en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatoYuiko en-aut-sei=Kato en-aut-mei=Yuiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsunodaAyaka en-aut-sei=Tsunoda en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiokaKunio en-aut-sei=Nishioka en-aut-mei=Kunio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanabeYoshinori en-aut-sei=Tanabe en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Faculty of Health Sciences, Department of Radiological Technology, Okayama University Medical School, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Health Sciences, Department of Radiological Technology, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Health Sciences, Department of Radiological Technology, Okayama University Medical School, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Health Sciences, Department of Radiological Technology, Okayama University Medical School, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Health Sciences, Department of Radiological Technology, Okayama University Medical School, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiology, Tokuyama Central Hospital kn-affil= affil-num=7 en-affil=Faculty of Medicine, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Dose calculation kn-keyword=Dose calculation en-keyword=Inter-facility variation kn-keyword=Inter-facility variation en-keyword=Low-density regions kn-keyword=Low-density regions en-keyword=Percentage depth dose kn-keyword=Percentage depth dose en-keyword=Radiation therapy planning system kn-keyword=Radiation therapy planning system END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=14 article-no= start-page=6927 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gain-of-function gene alterations in rearranged during transfection (RET), a receptor tyrosine kinase, are observed in both sporadic and hereditary medullary thyroid cancers (MTCs) and pheochromocytomas and paragangliomas (PPGLs). Several tyrosine kinase inhibitors (TKIs) that target RET have been proven to be effective on MTCs and PCCs. Recently, TKIs, namely, sunitinib and selpercatinib, which were clinically used to target PPGLs, have been reported to decrease catecholamine levels without reducing tumor size. Our clinical case of metastatic medullary thyroid cancer, which is associated with RET mutations undergoing treatment with vandetanib, also suggests that vandetanib can decrease catecholamine levels. Therefore, we investigated the effect of vandetanib, a representative multi-targeted TKI for RET-related MTC, on cell proliferation and catecholamine synthesis in rat pheochromocytoma PC12 cells. Vandetanib reduced viable cells in a concentration-dependent manner. The dopamine and noradrenaline levels of the cell lysate were reduced in a concentration-dependent manner. They also decreased more prominently at lower concentrations of vandetanib compared to the inhibition of cell proliferation. The RNA knockdown study of Ret revealed that this inhibitory effect on catecholamine synthesis is mainly mediated by the suppression of RET signaling. Next, we focused on two signaling pathways downstream of RET, namely, ERK and AKT signaling. Treatment with vandetanib reduced both ERK and AKT phosphorylation in PC12 cells. Moreover, both an MEK inhibitor U0126 and a PI3K/AKT inhibitor LY294002 suppressed catecholamine synthesis without decreasing viable cells. This study in rat pheochromocytoma PC12 cells reveals the direct inhibitory effects of vandetanib on catecholamine synthesis via the suppression of RET-ERK and RET-AKT signaling. en-copyright= kn-copyright= en-aut-name=ItohYoshihiko en-aut-sei=Itoh en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InagakiKenichi en-aut-sei=Inagaki en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TerasakaTomohiro en-aut-sei=Terasaka en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimotoEisaku en-aut-sei=Morimoto en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiiTakahiro en-aut-sei=Ishii en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamaokaKimitomo en-aut-sei=Yamaoka en-aut-mei=Kimitomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujisawaSatoshi en-aut-sei=Fujisawa en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=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= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=tyrosine kinase inhibitor kn-keyword=tyrosine kinase inhibitor en-keyword=multiple endocrine neoplasia type 2 kn-keyword=multiple endocrine neoplasia type 2 en-keyword=paraganglioma kn-keyword=paraganglioma en-keyword=RET kn-keyword=RET en-keyword=ERK kn-keyword=ERK en-keyword=AKT kn-keyword=AKT END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=7 article-no= start-page=319 end-page=325 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nationwide Survey of Middle Meningeal Artery Embolization for Chronic Subdural Hematoma in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Middle meningeal artery embolization has increasingly been used to treat chronic subdural hematoma. However, the current state of its application and outcomes in Japan remains unclear. We conducted a multicenter observational study involving facilities affiliated with the Japanese Society for Neuroendovascular Therapy to assess current practices and clarify the usefulness and safety of middle meningeal artery embolization for chronic subdural hematoma. A total of 466 patients from 40 facilities were included. The mean age of the patients was 78.0 } 10.5 years, and bleeding risks, including antithrombotic therapy or bleeding predisposition, were present in 36.1% of patients. The most common timing for middle meningeal artery embolization was after the second burr hole surgery, accounting for 34.8% of cases. N-butyl-2-cyanoacrylate was used as the embolic material in 67% of cases. The complication rate was 5.2%, with complication-related morbidity at 0.9%. Hematomas were stable in 91.5% of cases at 30 days post-middle meningeal artery embolization. The symptomatic recurrence rate was 8.9%. Cases that underwent middle meningeal artery embolization after the second or subsequent burr hole surgeries were significantly associated with symptomatic recurrence. This study is the first nationwide survey investigating the real-world clinical practice of middle meningeal artery embolization for chronic subdural hematoma in Japan. While it included many elderly patients, recurrent cases, and those with bleeding risks, the safety and usefulness of middle meningeal artery embolization were deemed acceptable. However, symptomatic recurrence was common even in cases with middle meningeal artery embolization when performed after the second or subsequent burr hole surgeries. A further prospective study will be warranted to clarify treatment indications, optimal timing, and treatment techniques of middle meningeal artery embolization. en-copyright= kn-copyright= en-aut-name=MURAISatoshi en-aut-sei=MURAI en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EBISUDANIYuki en-aut-sei=EBISUDANI en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HARUMAJun en-aut-sei=HARUMA en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HIRAMATSUMasafumi en-aut-sei=HIRAMATSU en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HISHIKAWATomohito en-aut-sei=HISHIKAWA en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SATOWTetsu en-aut-sei=SATOW en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SUGIUKenji en-aut-sei=SUGIU en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Neurosurgery, Kawasaki Medical School 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 Neurosurgery, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Neurosurgery/Stroke Center, Kindai University Hospital kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=chronic subdural hematoma kn-keyword=chronic subdural hematoma en-keyword=endovascular therapy kn-keyword=endovascular therapy en-keyword=middle meningeal artery kn-keyword=middle meningeal artery END start-ver=1.4 cd-journal=joma no-vol=351 cd-vols= no-issue= article-no= start-page=199522 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=Evidence for the replication of a plant rhabdovirus in its arthropod mite vector en-subtitle= kn-subtitle= en-abstract= kn-abstract=Transmission of plant viruses that replicate in the insect vector is known as persistent-propagative manner. However, it remains unclear whether such virus-vector relationships also occur between plant viruses and other biological vectors such as arthropod mites. In this study, we investigated the possible replication of orchid fleck virus (OFV), a segmented plant rhabdovirus, within its mite vector (Brevipalpus californicus s.l.) using quantitative RT-qPCR, western blotting and next-generation sequencing. Time-course RT-qPCR and western blot analyses showed an increasing OFV accumulation pattern in mites after virus acquisition. Since OFV genome expression requires the transcription of polyadenylated mRNAs, polyadenylated RNA fractions extracted from the viruliferous mite samples and OFV-infected plant leaves were used for RNA-seq analysis. In the mite and plant datasets, a large number of sequence reads were aligned to genomic regions of OFV RNA1 and RNA2 corresponding to transcribed viral gene mRNAs. This includes the short polyadenylated transcripts originating from the leader and trailer regions at the ends of the viral genome, which are believed to play a crucial role in viral transcription/replication. In contrast, a low number of reads were mapped to the non-transcribed regions (gene junctions). These results strongly suggested that OFV gene expression occurs both in mites and plants. Additionally, deep sequencing revealed the accumulation of OFV-derived small RNAs in mites, although their size profiles differ from those found in plants. Taken together, our results indicated that OFV replicates within a mite vector and is targeted by the RNA-silencing mechanism. en-copyright= kn-copyright= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujitaMiki en-aut-sei=Fujita en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TelengechPaul en-aut-sei=Telengech en-aut-mei=Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruyamKazuyuki en-aut-sei=Maruyam en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HyodoKiwamu en-aut-sei=Hyodo en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TassiAline Daniele en-aut-sei=Tassi en-aut-mei=Aline Daniele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OchoaRonald en-aut-sei=Ochoa en-aut-mei=Ronald kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndikaIda Bagus en-aut-sei=Andika en-aut-mei=Ida Bagus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=6 en-affil=Tropical Research and Education Center, University of Florida kn-affil= affil-num=7 en-affil=Systematic Entomology Laboratory, USDA kn-affil= affil-num=8 en-affil=College of Plant Protection, Northwest A&F University kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Rhabdovirus kn-keyword=Rhabdovirus en-keyword=Plant kn-keyword=Plant en-keyword=Mite kn-keyword=Mite en-keyword=Vector kn-keyword=Vector en-keyword=Replication kn-keyword=Replication en-keyword=mRNA kn-keyword=mRNA en-keyword=Small RNA kn-keyword=Small RNA END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page=902 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250711 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of an Antimicrobial Coating Film for Denture Lining Materials en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Denture hygiene is essential for the prevention of oral candidiasis, a condition frequently associated with Candida albicans colonization on denture surfaces. Cetylpyridinium chloride (CPC)-loaded montmorillonite (CPC-Mont) has demonstrated antimicrobial efficacy in tissue conditioners and demonstrates potential for use in antimicrobial coatings. In this study, we aimed to develop and characterize CPC-Mont-containing coating films for dentures, focusing on their physicochemical behaviors and antifungal efficacies. Methods: CPC was intercalated into sodium-type montmorillonite to prepare CPC-Mont; thereafter, films containing CPC-Mont were fabricated using emulsions of different polymer types (nonionic, cationic, and anionic). CPC loading, release, and recharging behaviors were assessed at various temperatures, and activation energies were calculated using Arrhenius plots. Antimicrobial efficacy against Candida albicans was evaluated for each film using standard microbial assays. Results: X-ray diffraction analysis confirmed the expansion of montmorillonite interlayer spacing by approximately 3 nm upon CPC loading. CPC-Mont showed temperature-dependent release and recharging behavior, with higher temperatures enhancing its performance. The activation energy for CPC release was 38 kJ/mol, while that for recharging was 26 kJ/mol. Nonionic emulsions supported uniform CPC-Mont dispersion and successful film formation, while cationic and anionic emulsions did not. CPC-Mont-containing coatings maintained antimicrobial activity against Candida albicans on dentures. Conclusions: CPC-Mont can be effectively incorporated into nonionic emulsion-based films to create antimicrobial coatings for denture applications. The films exhibited temperature-responsive, reversible CPC release and recharging behaviors, while maintaining antifungal efficacy, findings which suggest the potential utility of CPC-Mont-containing films as a practical strategy to prevent denture-related candidiasis. en-copyright= kn-copyright= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KameyamaTakeru en-aut-sei=Kameyama en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Van MeerbeekBart en-aut-sei=Van Meerbeek en-aut-mei=Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkiharaTakumi en-aut-sei=Okihara en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Dental School, Advanced Research Center for Oral and Craniofacial Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=5 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=BIOMAT, Department of Oral Health Sciences, KU Leuvem kn-affil= affil-num=7 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=antimicrobial kn-keyword=antimicrobial en-keyword=denture liner kn-keyword=denture liner en-keyword=cetylpyridiniumchloride kn-keyword=cetylpyridiniumchloride en-keyword=drug release kn-keyword=drug release en-keyword=drug recharge kn-keyword=drug recharge END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=5 article-no= start-page=e70046 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spider mite tetranins elicit different defense responses in different host habitats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spider mites (Tetranychus urticae) are a major threat to economically important crops. Here, we investigated the potential of tetranins, in particular Tet3 and Tet4, as T. urticae protein-type elicitors that stimulate plant defense. Truncated Tet3 and Tet4 proteins showed efficacy in activating the defense gene pathogenesis-related 1 (PR1) and inducing phytohormone production in leaves of Phaseolus vulgaris. In particular, Tet3 caused a drastically higher Ca2+ influx in leaves, but a lower reactive oxygen species (ROS) generation compared to other tetranins, whereas Tet4 caused a low Ca2+ influx and a high ROS generation in the host plants. Such specific and non-specific elicitor activities were examined by knockdown of Tet3 and Tet4 expressions in mites, confirming their respective activities and in particular showing that they function additively or synergistically to induce defense responses. Of great interest is the fact that Tet3 and Tet4 expression levels were higher in mites on their preferred host, P. vulgaris, compared to the levels in mites on the less-preferred host, Cucumis sativus, whereas Tet1 and Tet2 were constitutively expressed regardless of their host. Furthermore, mites that had been hosted on C. sativus induced lower levels of PR1 expression, Ca2+ influx and ROS generation, i.e., Tet3- and Tet4-responsive defense responses, in both P. vulgaris and C. sativus leaves compared to the levels induced by mites that had been hosted on P. vulgaris. Taken together, these findings show that selected tetranins respond to variable host cues that may optimize herbivore fitness by altering the anti-mite response of the host plant. en-copyright= kn-copyright= en-aut-name=EndoYukiko en-aut-sei=Endo en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaMiku en-aut-sei=Tanaka en-aut-mei=Miku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UemuraTakuya en-aut-sei=Uemura en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanimuraKaori en-aut-sei=Tanimura en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DesakiYoshitake en-aut-sei=Desaki en-aut-mei=Yoshitake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzawaRika en-aut-sei=Ozawa en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BonzanoSara en-aut-sei=Bonzano en-aut-mei=Sara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaffeiMassimo E. en-aut-sei=Maffei en-aut-mei=Massimo E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShinyaTomonori en-aut-sei=Shinya en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GalisIvan en-aut-sei=Galis en-aut-mei=Ivan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ArimuraGen]ichiro en-aut-sei=Arimura en-aut-mei=Gen]ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=2 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=3 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=4 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=5 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=6 en-affil=Center for Ecological Research, Kyoto University kn-affil= affil-num=7 en-affil=Department of Life Sciences and Systems Biology, Plant Physiology Unit, University of Turin kn-affil= affil-num=8 en-affil=Department of Life Sciences and Systems Biology, Plant Physiology Unit, University of Turin kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=11 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= en-keyword=Cucumis sativus kn-keyword=Cucumis sativus en-keyword=elicitor kn-keyword=elicitor en-keyword=Phaseolus vulgaris kn-keyword=Phaseolus vulgaris en-keyword=spider mite (Tetranychus urticae) kn-keyword=spider mite (Tetranychus urticae) en-keyword=tetranin kn-keyword=tetranin END start-ver=1.4 cd-journal=joma no-vol=637 cd-vols= no-issue=8046 article-no= start-page=744 end-page=748 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= kn-title=Centrophilic retrotransposon integration via CENH3 chromatin in Arabidopsis en-subtitle= kn-subtitle= en-abstract= kn-abstract=In organisms ranging from vertebrates to plants, major components of centromeres are rapidly evolving repeat sequences, such as tandem repeats (TRs) and transposable elements (TEs), which harbour centromere-specific histone H3 (CENH3)1,2. Complete centromere structures recently determined in human and Arabidopsis suggest frequent integration and purging of retrotransposons within the TR regions of centromeres3,4,5. Despite the high impact of ecentrophilicf retrotransposons on the paradox of rapid centromere evolution, the mechanisms involved in centromere targeting remain poorly understood in any organism. Here we show that both Ty3 and Ty1 long terminal repeat retrotransposons rapidly turnover within the centromeric TRs of Arabidopsis species. We demonstrate that the Ty1/Copia element Tal1 (Transposon of Arabidopsis lyrata 1) integrates de novo into regions occupied by CENH3 in Arabidopsis thaliana, and that ectopic expansion of the CENH3 region results in spread of Tal1 integration regions. The integration spectra of chimeric TEs reveal the key structural variations responsible for contrasting chromatin-targeting specificities to centromeres versus gene-rich regions, which have recurrently converted during the evolution of these TEs. Our findings show the impact of centromeric chromatin on TE-mediated rapid centromere evolution, with relevance across eukaryotic genomes. en-copyright= kn-copyright= en-aut-name=TsukaharaSayuri en-aut-sei=Tsukahara en-aut-mei=Sayuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BousiosAlexandros en-aut-sei=Bousios en-aut-mei=Alexandros kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Perez-RomanEstela en-aut-sei=Perez-Roman en-aut-mei=Estela kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamaguchiSota en-aut-sei=Yamaguchi en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LeduqueBasile en-aut-sei=Leduque en-aut-mei=Basile kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoAimi en-aut-sei=Nakano en-aut-mei=Aimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaishMatthew en-aut-sei=Naish en-aut-mei=Matthew kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OsakabeAkihisa en-aut-sei=Osakabe en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyodaAtsushi en-aut-sei=Toyoda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHidetaka en-aut-sei=Ito en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EderaAlejandro en-aut-sei=Edera en-aut-mei=Alejandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TominagaSayaka en-aut-sei=Tominaga en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Juliarni en-aut-sei=Juliarni en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatoKae en-aut-sei=Kato en-aut-mei=Kae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OdaShoko en-aut-sei=Oda en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InagakiSoichi en-aut-sei=Inagaki en-aut-mei=Soichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Lorkovi?Zdravko en-aut-sei=Lorkovi? en-aut-mei=Zdravko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NagakiKiyotaka en-aut-sei=Nagaki en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=BergerFr?d?ric en-aut-sei=Berger en-aut-mei=Fr?d?ric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KawabeAkira en-aut-sei=Kawabe en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=QuadranaLeandro en-aut-sei=Quadrana en-aut-mei=Leandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HendersonIan en-aut-sei=Henderson en-aut-mei=Ian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KakutaniTetsuji en-aut-sei=Kakutani en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=2 en-affil=School of Life Sciences, University of Sussex kn-affil= affil-num=3 en-affil=School of Life Sciences, University of Sussex kn-affil= affil-num=4 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=Institute of Plant Sciences Paris]Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour lfAgriculture, lfAlimentation et lfEnvironnement, Universit? Evry, Universit? Paris kn-affil= affil-num=6 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=8 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=9 en-affil=Center for Genetic Resource Information, National Institute of Genetics kn-affil= affil-num=10 en-affil=Faculty of Science, Hokkaido University kn-affil= affil-num=11 en-affil=Institute of Plant Sciences Paris]Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour lfAgriculture, lfAlimentation et lfEnvironnement, Universit? Evry, Universit? Paris kn-affil= affil-num=12 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=13 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Integrated Genetics, National Institute of Genetics kn-affil= affil-num=15 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=16 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=17 en-affil=Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC) kn-affil= affil-num=18 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=19 en-affil=Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC) kn-affil= affil-num=20 en-affil=Faculty of Life Sciences, Kyoto Sangyo University kn-affil= affil-num=21 en-affil=Institute of Plant Sciences Paris]Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour lfAgriculture, lfAlimentation et lfEnvironnement, Universit? Evry, Universit? Paris kn-affil= affil-num=22 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=23 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=186 cd-vols= no-issue= article-no= start-page=118030 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=(+)-Terrein exerts anti-obesity and anti-diabetic effects by regulating the differentiation and thermogenesis of brown adipocytes in mice fed a high-fat diet en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: (+)-Terrein, a low-molecular-weight secondary metabolite from Aspergillus terreus, inhibits adipocyte differentiation in vitro. However, the precise mechanisms underlying the effects of (+)-terrein on adipocytes remain unclear. We hypothesized that (+)-terrein modulates adipogenesis and glucose homeostasis in obesity and diabetes via anti-inflammatory action and regulation of adipocyte differentiation. Hence, in this study, we aimed to investigate the in vivo anti-diabetic and anti-obesity effects of (+)-terrein.
Methods: Male C57BL/6?J mice were fed normal chow or high-fat (HF) diet and administered (+)-terrein (180?mg/kg) via intraperitoneal injection. Glucose and insulin tolerance tests, serum biochemical assays, and histological analyses were also performed. Rat brown preadipocytes, mouse brown preadipocytes (T37i cells), and inguinal white adipose tissue (ingWAT) preadipocytes were exposed to (+)-terrein during in vitro adipocyte differentiation. Molecular markers associated with thermogenesis and differentiation were quantified using real-time polymerase chain reaction and western blotting.
Results: (+)-Terrein-treated mice exhibited improved insulin sensitivity and reduced serum lipid and glucose levels, irrespective of the diet. Furthermore, (+)-terrein suppressed body weight gain and mitigated fat accumulation by activating brown adipose tissue in HF-fed mice. (+)-Terrein facilitated the in vitro differentiation of rat brown preadipocytes, T37i cells, and ingWAT preadipocytes by upregulating peroxisome proliferator-activated receptor-ƒÁ (PPARƒÁ). This effect was synergistic with that of a PPARƒÁ agonist.
Conclusion: This study demonstrated that (+)-terrein effectively induces PPARƒÁ expression and brown adipocyte differentiation, leading to reduced weight gain and improved glucose and lipid profiles in HF-fed mice. Thus, (+)-terrein is a potent novel agent with potential anti-obesity and anti-diabetic properties. en-copyright= kn-copyright= en-aut-name=Aoki-SaitoHaruka en-aut-sei=Aoki-Saito en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MandaiHiroki en-aut-sei=Mandai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakakuraTakashi en-aut-sei=Nakakura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiTsutomu en-aut-sei=Sasaki en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraTadahiro en-aut-sei=Kitamura en-aut-mei=Tadahiro 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=HisadaTakeshi en-aut-sei=Hisada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkadaShuichi en-aut-sei=Okada en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaMasanobu en-aut-sei=Yamada en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaitoTsugumichi en-aut-sei=Saito en-aut-mei=Tsugumichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=3 en-affil=Department of Anatomy, Teikyo University School of Medicine kn-affil= affil-num=4 en-affil=Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University 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=Gunma University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Diabetes, Soleiyu Asahi Clinic kn-affil= affil-num=9 en-affil=Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University kn-affil= affil-num=10 en-affil=Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei University kn-affil= en-keyword=(+)-Terrein kn-keyword=(+)-Terrein en-keyword=Brown adipose tissue kn-keyword=Brown adipose tissue en-keyword=Thermogenesis kn-keyword=Thermogenesis en-keyword=Obesity kn-keyword=Obesity en-keyword=PPARƒÁ kn-keyword=PPARƒÁ END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e00678 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alkoxy]Substituted Anthrabis(Thiadiazole)]Terthiophene Copolymers for Organic Photovoltaics: A Unique Wavy Backbone Enhances Aggregation, Molecular Order, and Device Efficiency en-subtitle= kn-subtitle= en-abstract= kn-abstract=Two polymer donors, PATz3T-o6BO and PATz3T-o6HD, incorporating alkoxy-substituted anthra[1,2-c:5,6-cŒ]bis([1,2,5]thiadiazole), were strategically designed and synthesized. The unique wavy backbone of these polymers effectively reduced aggregation, leading to enhanced solubility and significantly improved molecular ordering. Consequently, the PATz3T-o6HD:Y12-based solar cells achieved a power conversion efficiency (PCE) of 7.94%. These findings provide valuable insights into the molecular design of high-performance polymer donors for organic photovoltaics (OPVs). en-copyright= kn-copyright= en-aut-name=YanYi en-aut-sei=Yan en-aut-mei=Yi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriHiroki en-aut-sei=Mori en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshinoTomoki en-aut-sei=Yoshino en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InamiRyuki en-aut-sei=Inami en-aut-mei=Ryuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChangJiaxin en-aut-sei=Chang en-aut-mei=Jiaxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GaoJunqing en-aut-sei=Gao en-aut-mei=Junqing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiharaYasushi en-aut-sei=Nishihara en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, 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=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=Aggregation kn-keyword=Aggregation en-keyword=Backbone conformation kn-keyword=Backbone conformation en-keyword=Conjugated polymers kn-keyword=Conjugated polymers en-keyword=Organic solar cells kn-keyword=Organic solar cells en-keyword=Semiconducting polymers kn-keyword=Semiconducting polymers END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=10712 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Shoot-Silicon-Signal protein to regulate root silicon uptake in rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plants accumulate silicon to protect them from biotic and abiotic stresses. Especially in rice (Oryza sativa), a typical Si-accumulator, tremendous Si accumulation is indispensable for healthy growth and productivity. Here, we report a shoot-expressed signaling protein, Shoot-Silicon-Signal (SSS), an exceptional homolog of the flowering hormone gflorigenh differentiated in Poaceae. SSS transcript is only detected in the shoot, whereas the SSS protein is also detected in the root and phloem sap. When Si is supplied from the root, the SSS transcript rapidly decreases, and then the SSS protein disappears. In sss mutants, root Si uptake and expression of Si transporters are decreased to a basal level regardless of the Si supply. The grain yield of the mutants is decreased to 1/3 due to insufficient Si accumulation. Thus, SSS is a key phloem-mobile protein for integrating root Si uptake and shoot Si accumulation underlying the terrestrial adaptation strategy of grasses. en-copyright= kn-copyright= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Mitani-UenoNamiki en-aut-sei=Mitani-Ueno en-aut-mei=Namiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiToshiki en-aut-sei=Fujii en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinyaTomonori en-aut-sei=Shinya en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShaoJi Feng en-aut-sei=Shao en-aut-mei=Ji Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WatanukiShota en-aut-sei=Watanuki en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitohYasunori en-aut-sei=Saitoh en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture & Forestry 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=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=12857 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250414 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=OsPIP2;4 aquaporin water channel primarily expressed in roots of rice mediates both water and nonselective Na+ and K+ conductance en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aquaporin (AQP)-dependent water transport across membranes is indispensable in plants. Recent evidence shows that several AQPs, including plasma membrane intrinsic proteins (PIPs), facilitate the electrogenic transport of ions as well as water transport and are referred to as ion-conducting aquaporins (icAQPs). The present study attempted to identify icAQPs that exhibit cation transport activity among PIPs from rice. Electrophysiological experiments on 11 OsPIPs using Xenopus laevis oocytes revealed that OsPIP2;4 mediated the electrogenic transport of alkali monovalent cations with the selectivity sequence of Na+ ? K+ > Rb+ > Cs+ > Li+, suggesting non-selective cation conductance for Na+ and K+. Transcripts of OsPIP2;4 were abundant in the elongation and mature zones of roots with similar expression levels between the root stelar and remaining outer parts in the cultivar Nipponbare. Immunostaining using sections of the crown roots of Nipponbare plants revealed the expression of OsPIP2;4 in the exodermis and sclerenchyma of the surface region and in the endodermis and pericycle of the stelar region. The present results provide novel insights into OsPIP2;4-dependent non-selective Na+ and K+ transport and its physiological roles in rice. en-copyright= kn-copyright= en-aut-name=TranSen Thi Huong en-aut-sei=Tran en-aut-mei=Sen Thi Huong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitoYunosuke en-aut-sei=Mito en-aut-mei=Yunosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnishiAya en-aut-sei=Onishi en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HigaAyaka en-aut-sei=Higa en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnoShuntaro en-aut-sei=Ono en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PaulNewton Chandra en-aut-sei=Paul en-aut-mei=Newton Chandra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HorieRie en-aut-sei=Horie en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HaradaYoshihiko en-aut-sei=Harada en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HorieTomoaki en-aut-sei=Horie en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=8 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=9 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=10 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= en-keyword=Ion-conducting Aquaporins kn-keyword=Ion-conducting Aquaporins en-keyword=Non-selective cation channel kn-keyword=Non-selective cation channel en-keyword=Rice kn-keyword=Rice en-keyword=Roots kn-keyword=Roots 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=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amino Acid Substitutions in Loop C of Arabidopsis PIP2 Aquaporins Alters the Permeability of CO2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The transport of CO2 across biomembranes in plant cells is essential for efficient photosynthesis. Some aquaporins capable of CO2 transport, referred to as eCOOporinsf, are postulated to play a crucial role in leaf CO2 diffusion. However, the structural basis of CO2 permeation through aquaporins remains largely unknown. Here, we show that amino acids in loop C are critical for the CO2 permeability of Arabidopsis thaliana PIP2 aquaporins. We found that swapping tyrosine and serine in loop C to histidine and phenylalanine, which differ between AtPIP2;1 and AtPIP2;3, altered CO2 permeability when examined in the Xenopus laevis oocyte heterologous expression system. AlphaFold2 modelling indicated that these substitution induced a conformational shift in the sidechain of arginine in the aromatic/arginine (ar/R) selectivity filter and in lysine at the extracellular mouth of the monomeric pore in PIP2 aquaporins. Our findings demonstrate that distal amino acid substitutions can trigger conformational changes of the ar/R filter in the monomeric pore, modulating CO2 permeability. Additionally, phylogenetic analysis suggested that aquaporins capable of dual water/CO2 permeability are ancestral to those that are water-selective and CO2-impermeable, and CO2-selective and water impermeable. en-copyright= kn-copyright= en-aut-name=TaniaShaila Shermin en-aut-sei=Tania en-aut-mei=Shaila Shermin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UtsugiShigeko en-aut-sei=Utsugi en-aut-mei=Shigeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchiyaYoshiyuki en-aut-sei=Tsuchiya en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasanoShizuka en-aut-sei=Sasano en-aut-mei=Shizuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=CO2 transport kn-keyword=CO2 transport en-keyword=monomeric pore kn-keyword=monomeric pore en-keyword=PIP2 aquaporin kn-keyword=PIP2 aquaporin en-keyword=Xenopus laevis kn-keyword=Xenopus laevis END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=23 article-no= start-page=17720 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=A meta-linked isomer of ITIC: influence of aggregation patterns on open-circuit voltage in organic solar cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Improving the open-circuit voltage (VOC) of organic solar cells (OSCs) remains an important challenge. While it is known that the energy levels at the donor/acceptor (D/A) interface affect the VOC, the impact of aggregation patterns on the energy levels at the D/A interface has not been fully elucidated. Herein, we focus on ITIC, a widely used acceptor in OSCs, and designed a meta-linked isomer of ITIC (referred to as im-ITIC) to alter molecular symmetry and modify substitution arrangements. Concentration-dependent 1H NMR spectra revealed that im-ITIC shows stronger aggregation behavior in solution. Single-crystal X-ray analysis showed that im-ITIC forms both tail-to-tail (J-aggregation) and face-to-face (H-aggregation) stacking modes, whereas ITIC exclusively forms tail-to-tail stacking. OSCs based on PBDB-T:im-ITIC showed a high VOC value of 1.02 V, which is 0.12 V higher than that of those based on PBDB-T:ITIC. Time-resolved infrared measurements revealed the lifetime of free electrons for the pristine and blend films. The energy levels of the charge transfer state (ECT) for PBDB-T:im-ITIC- and PBDB-T:ITIC OSCs were determined to be 1.57 and 1.39 eV, respectively, correlating with the VOC values. Theoretical calculations indicated that pronounced H-aggregation in im-ITIC increases the ECT compared with J-aggregation, contributing to the improved VOC. This study underscores the critical impact of molecular aggregation patterns on energy alignment and VOC enhancement, offering insights into molecular design for achieving high VOC in OSCs. en-copyright= kn-copyright= en-aut-name=WangKai en-aut-sei=Wang en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JinnaiSeihou en-aut-sei=Jinnai en-aut-mei=Seihou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UesakaKaito en-aut-sei=Uesaka en-aut-mei=Kaito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamakataAkira en-aut-sei=Yamakata en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IeYutaka en-aut-sei=Ie en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka kn-affil= affil-num=2 en-affil=The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka kn-affil= affil-num=3 en-affil=Graduate School of Natural Science & Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science & Technology, Okayama University kn-affil= affil-num=5 en-affil=The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka kn-affil= END start-ver=1.4 cd-journal=joma no-vol=158 cd-vols= no-issue= article-no= start-page=107932 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trends in nontuberculous mycobacterial disease mortality based on 2000-2022 data from 83 countries en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To examine the international trends for nontuberculous mycobacterial-associated mortality rates, as nontuberculous mycobacterial infections are becoming increasingly prevalent and pose a significant public health challenge, especially in older populations.
Methods: This retrospective observational study used data from the World Health Organization mortality database, which included patients with nontuberculous mycobacterial infection in 83 countries. We stratified the data by sex, age, and geographic region and calculated crude and age-standardized mortality rates to estimate long-term mortality trends.
Results: In total, 42,182 nontuberculous mycobacterial infection-associated deaths (58.1% in women) were reported in 83 countries between 2000 and 2022. The locally weighted regression model estimation for the nontuberculous mycobacterial infection-associated mortality rate more than doubled?from 0.36 deaths per 1000,000 individuals in 2000 to 0.77 deaths per 1000,000 individuals in 2022. Eighty-six percent of nontuberculous mycobacterial infection-associated deaths occurred in people aged ?65 years. The mortality rate was the highest in the Western Pacific Region.
Conclusion: This study highlights the impact of emerging nontuberculous mycobacterial diseases and the importance of targeted interventions for managing and reducing mortality, particularly in vulnerable older populations. Further studies are warranted to determine the factors contributing to geographical disparity and treatment options. en-copyright= kn-copyright= en-aut-name=HaradaKo en-aut-sei=Harada en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=VuQuynh Thi en-aut-sei=Vu en-aut-mei=Quynh Thi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MinatoYusuke en-aut-sei=Minato en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=2 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Hematology/Oncology, Mayo Clinic kn-affil= affil-num=4 en-affil=Department of Education and Research Centre for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Center for Infectious Disease Research, Fujita Health University kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Population surveillance kn-keyword=Population surveillance en-keyword=Mortality kn-keyword=Mortality en-keyword=Nontuberculous mycobacterial infections kn-keyword=Nontuberculous mycobacterial infections END start-ver=1.4 cd-journal=joma no-vol=262 cd-vols= no-issue=2 article-no= start-page=385 end-page=395 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analysis of the effect of permeant solutes on the hydraulic resistance of the plasma membrane in cells of Chara corallina en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the cells of Chara corallina, permeant monohydric alcohols including methanol, ethanol and 1-propanol increased the hydraulic resistance of the membrane (Lpm?1). We found that the relative value of the hydraulic resistance (rLpm?1) was linearly dependent on the concentration (Cs) of the alcohol. The relationship is expressed in the equation: rLpm?1?=?ƒÏmCs?+?1, where ƒÏm is the hydraulic resistance modifier coefficient of the membrane. Ye et al. (2004) showed that membrane-permeant glycol ethers also increased Lp?1. We used their data to estimate Lpm?1 and rLpm?1. The values of rLpm?1 fit the above relation we found for alcohols. When we plotted the ƒÏm values of all the permeant alcohols and glycol ethers against their molecular weights (MW), we obtained a linear curve with a slope of 0.014 M?1/MW and with a correlation coefficient of 0.99. We analyzed the influence of the permeant solutes on the relative hydraulic resistance of the membrane (rLpm?1) as a function of the external (ƒÎ0) and internal (ƒÎi) osmotic pressures. The analysis showed that the hydraulic resistance modifier coefficients (ƒÏm) were linearly related to the MW of the permeant solutes with a slope of 0.012 M?1/MW and with a correlation coefficient of 0.84. The linear relationship between the effects of permeating solutes on the hydraulic resistance modifier coefficient (ƒÏm) and the MW can be explained in terms of the effect of the effective osmotic pressure on the hydraulic conductivity of water channels. The result of the analysis suggests that the osmotic pressure and not the size of the permeant solute as proposed by (Ye et al., J Exp Bot 55:449?461, 2004) is the decisive factor in a solutefs influence on hydraulic conductivity. Thus, characean water channels (aquaporins) respond to permeant solutes with essentially the same mechanism as to impermeant solutes. en-copyright= kn-copyright= en-aut-name=TazawaMasashi en-aut-sei=Tazawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WayneRandy en-aut-sei=Wayne en-aut-mei=Randy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Yoshida Biological Laboratory kn-affil= affil-num=2 en-affil=Laboratory of Natural Philosophy, Plant Biology Section, Cornell University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Chara corallina kn-keyword=Chara corallina en-keyword=Effective osmotic pressure kn-keyword=Effective osmotic pressure en-keyword=Hydraulic resistance kn-keyword=Hydraulic resistance en-keyword=Plasma membrane kn-keyword=Plasma membrane en-keyword=Reflection coefficient kn-keyword=Reflection coefficient END start-ver=1.4 cd-journal=joma no-vol=599 cd-vols= no-issue=13 article-no= start-page=1914 end-page=1924 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250525 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characterization of molecular mechanisms of CaMKKƒ¿/1 oligomerization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is an activating kinase for calcium/calmodulin-dependent protein kinase type 1 (CaMKI), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), RAC-alpha serine/threonine-protein kinase (PKB), and AMP-activated protein kinase (AMPK) that has been reported to form an active oligomer in cells. Glutathione S-transferase (GST) pulldown assay from the extracts of COS-7 cells expressing GST- and His6-CaMKKƒ¿/1 mutants showed that the C-terminal region containing the autoinhibitory and calmodulin (CaM)-binding sequence (residues 438?463) is required for CaMKKƒ¿/1 homo-oligomerization. This was confirmed by the fact that the GST-CaMKKƒ¿/1 C-terminal domain (residues 435?505) directly interacted with EGFP-CaMKKƒ¿/1 residues 435?505 as well as with wild-type CaMKKƒ¿/1. Notably, once oligomerized in cells, CaMKKƒ¿/1 is neither exchangeable between the oligomeric complexes nor dissociated by Ca2+/CaM binding. These results support stable oligomerization of CaMKK in the cells by intermolecular self-association of its C-terminal region containing a regulatory domain. en-copyright= kn-copyright= en-aut-name=UenoyamaShun en-aut-sei=Uenoyama en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NittaHayato en-aut-sei=Nitta en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuizuFutoshi en-aut-sei=Suizu en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokumitsuHiroshi en-aut-sei=Tokumitsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=3 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Medical Technology, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=6 en-affil= kn-affil= en-keyword=calmodulin kn-keyword=calmodulin en-keyword=calmodulin-kinase cascade kn-keyword=calmodulin-kinase cascade en-keyword=CaMKKa/ kn-keyword=CaMKKa/ en-keyword=oligomerization kn-keyword=oligomerization en-keyword=protein?protein interaction kn-keyword=protein?protein interaction en-keyword=regulatory domain kn-keyword=regulatory domain END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=5 article-no= start-page=705 end-page=721 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SHORT AND CROOKED AWN, encoding the epigenetic regulator EMF1, promotes barley awn development en-subtitle= kn-subtitle= en-abstract= kn-abstract=The awn is a bristle-like extension from the tip of the lemma in grasses. In barley, the predominant cultivars possess long awns that contribute to grain yield and quality through photosynthesis. In addition, various awn morphological mutants are available in barley, rendering it a useful cereal crop to investigate the mechanims of awn development. Here, we identified the gene causative of the short and crooked awn (sca) mutant, which exhibits a short and curved awn phenotype. Intercrossing experiments revealed that the sca mutant induced in the Japanese cultivar (cv.) gAkashinrikih is allelic to the independently isolated moderately short-awn mutant breviaristatum-a (ari-a). Map-based cloning and sequencing revealed that SCA encodes the Polycomb group?associated protein EMBRYONIC FLOWER 1. We found that SCA affects awn development through the promotion of cell proliferation, elongation, and cell wall synthesis. RNA sequencing of cv. Bowman backcross-derived near-isogenic lines of sca and ari-a6 alleles showed that SCA is directly or indirectly involved in promoting the expression of genes related to awn development. Additionally, SCA represses various transcription factors essential for floral organ development and plant architecture, such as MADS-box and Knotted1-like homeobox genes. Notably, the repression of the C-class MADS-box gene HvMADS58 by SCA in awns is associated with the accumulation of the repressive histone modification H3K27me3. These findings highlight the potential role of SCA-mediated gene regulation, including histone modification, as a novel pathway in barley awn development. en-copyright= kn-copyright= en-aut-name=NakamuraKoki en-aut-sei=Nakamura en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiYuichi en-aut-sei=Kikuchi en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiragaMizuho en-aut-sei=Shiraga en-aut-mei=Mizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KotakeToshihisa en-aut-sei=Kotake en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HyodoKiwamu en-aut-sei=Hyodo en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaketaShin en-aut-sei=Taketa en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkedaYoko en-aut-sei=Ikeda en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Science and Engineering, Saitama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=barley kn-keyword=barley en-keyword=awn development kn-keyword=awn development en-keyword=EMBRYONIC FLOWER 1 (EMF1) kn-keyword=EMBRYONIC FLOWER 1 (EMF1) en-keyword=homeotic genes kn-keyword=homeotic genes en-keyword=H3K27 trimethylation kn-keyword=H3K27 trimethylation en-keyword=epigenetic regulation kn-keyword=epigenetic regulation 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=20250710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tumor Microvessels with Specific Morphology as a Prognostic Factor in Esophageal Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Angiogenesis is essential for tumor progression. Microvessel density (MVD) is a widely used histological method to assess angiogenesis using immunostained sections, but its prognostic significance in esophageal cancer remains controversial. Recently, the evaluation of microvascular architecture has gained importance as a method to assess tumor aggressiveness. The present study aimed to identify the histological characteristics of tumor microvessels that are associated with the aggressiveness of esophageal squamous cell carcinoma.
Patients and Methods A total of 108 esophageal squamous cell carcinoma tissues were immunohistochemically stained with blood vessel markers and angiogenesis-related markers, including CD31, alpha smooth muscle actin, vascular endothelial growth factor A (VEGF-A), CD206, and D2-40. MVD, microvessel pericyte coverage index (MPI), and tumor vascular morphology were evaluated by microscopy.
Results MVD was significantly associated with patient outcomes, whereas neither MPI nor VEGF-A expression throughout the tumor showed a significant correlation. In addition, the presence of blood vessels encircling clusters of tumor cells, termed C-shaped microvessels, and excessively branching microvessels, termed X-shaped microvessels, was significantly associated with poor prognosis. These vessel types were also correlated with clinicopathological parameters, including deeper invasion of the primary tumor, presence of lymph node metastasis, advanced pathological stage, and distant metastasis. Focal VEGF-A immunoexpression in tumor cells was higher in areas containing C-shaped or X-shaped microvessels compared with areas lacking these vessel morphologies.
Conclusions The data suggest that tumor microvessels with specific morphologies (C-shaped and X-shaped microvessels) may serve as a promising prognostic factor in esophageal squamous cell carcinoma. en-copyright= kn-copyright= en-aut-name=TunHnin Thida en-aut-sei=Tun en-aut-mei=Hnin Thida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=NishimuraSeitaro en-aut-sei=Nishimura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi 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=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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 Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Esophageal neoplasms kn-keyword=Esophageal neoplasms en-keyword=Angiogenesis kn-keyword=Angiogenesis en-keyword=Microvessel density kn-keyword=Microvessel density en-keyword=Pericytes kn-keyword=Pericytes en-keyword=VEGF-A kn-keyword=VEGF-A en-keyword=Immunohistochemistry kn-keyword=Immunohistochemistry en-keyword=Prognosis kn-keyword=Prognosis END start-ver=1.4 cd-journal=joma no-vol=177 cd-vols= no-issue=4 article-no= start-page=e70396 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=CNGC2 Negatively Regulates Stomatal Closure and Is Not Required for flg22- and H2O2-Induced Guard Cell [Ca2+]cyt Elevation in Arabidopsis thaliana en-subtitle= kn-subtitle= en-abstract= kn-abstract=In guard cells, cytosolic Ca2+ acts as a second messenger that mediates abscisic acid (ABA)- and pathogen-associated molecular pattern (PAMP)-induced stomatal closure. It was reported that Arabidopsis cyclic nucleotide-gated ion channel 2 (CNGC2) functions as hydrogen peroxide (H2O2)- and PAMP-activated Ca2+-permeable channels at the plasma membrane of mesophyll cells and mediates Ca2+-dependent PAMP-triggered immunity. In this study, we examined the role of CNGC2 in the regulation of stomatal movement because CNGC2 is also expressed in guard cells. We found that stomata of the CNGC2 disruption mutant cngc2-3 are constitutively closed even in the absence of ABA or the flagellar-derived PAMP, flg22. Consistently, leaf temperatures of the cngc2-3 mutant were higher than those of wild-type (WT) plants. The stomatal phenotype of the cngc2-3 mutant was restored by complementation with wild-type CNGC2 under the control of the guard cell preferential promoter, pGC1. Elevation of cytosolic free Ca2+ concentration in guard cells induced by flg22 and H2O2 remained intact in the cngc2-3 mutant. The introduction of the ost1-3 mutation into the cngc2-3 background did not alter the stomatal phenotype. However, the stomatal phenotype of the cngc2-3 mutant was successfully rescued in the double disruption mutant cngc2-3aba2-2. Taken together, these results suggest that CNGC2 negatively regulates stomatal closure response and does not function as flg22? and H2O2-activated Ca2+ channels in guard cells. Though CNGC2 is responsive for H2O2- and flg22-induced [Ca2+]cyt elevation in mesophyll cells, the involvement of CNGC2 in the response to H2O2 and flg22 in guard cells is questionable. en-copyright= kn-copyright= en-aut-name=AkterRojina en-aut-sei=Akter en-aut-mei=Rojina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueYasuhiro en-aut-sei=Inoue en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MasumotoSaori en-aut-sei=Masumoto en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MimataYoshiharu en-aut-sei=Mimata en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuuraTakakazu en-aut-sei=Matsuura en-aut-mei=Takakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraToshiyuki en-aut-sei=Nakamura en-aut-mei=Toshiyuki 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=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MunemasaShintaro en-aut-sei=Munemasa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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 Agriculture, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil= 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 Environmental and Life Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=calcium signaling kn-keyword=calcium signaling en-keyword=CNGC kn-keyword=CNGC en-keyword=stomata kn-keyword=stomata END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=13 article-no= start-page=9595 end-page=9603 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250616 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microagglomerate of VO2 Particles Packing Paraffin Wax Using Capillary Force as a Latent Thermal Energy Storage Medium en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study proposed a material to retain paraffin wax with vanadium dioxide (VO2) particles as a latent thermal energy storage medium, an alternative to core?shell microcapsules containing phase change materials. VO2 microparticles, which were synthesized through a sol?gel method and annealing process, were dispersed in the oil-in-water microemulsion to obtain microagglomerates of VO2 microparticles. The average diameter of microagglomerates was 5 ƒÊm, and they retained paraffin wax at the vacancies among VO2 particles. Although the microagglomerates had no complete shells similar to core?shell microcapsules, the microagglomerates successfully trapped paraffin wax droplets without any leakage even in a high-temperature environment. It was because capillary forces acting among VO2 particles strictly prevented any leakage of paraffin waxes. The differential scanning calorimetry revealed that the microagglomerates contained only 16.5 wt % of n-octadecane, used as a paraffin wax. However, since VO2 particles can release or absorb latent heat due to their metal?insulator phase transition, the proposed microagglomerates exhibited higher thermal energy storage densities than phase change microcapsules whose shells do not show phase transitions. Moreover, the microagglomerates exhibited higher thermal conductivity than microcapsules with amorphous inorganic shells because the VO2 particles were crystallized through annealing. The proposed microagglomerate is a promising form for further improving the thermal energy storage density and thermal performance of the latent thermal energy storage medium, especially in the temperature range of 30 to 70 ‹C. en-copyright= kn-copyright= en-aut-name=IsobeKazuma en-aut-sei=Isobe en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamauchiKaketo en-aut-sei=Yamauchi en-aut-mei=Kaketo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaYutaka en-aut-sei=Yamada en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HoribeAkihiko en-aut-sei=Horibe en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Faculty 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=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=microagglomerate kn-keyword=microagglomerate en-keyword=vanadium dioxide kn-keyword=vanadium dioxide en-keyword=paraffin wax kn-keyword=paraffin wax en-keyword=latent thermal energy storage medium kn-keyword=latent thermal energy storage medium en-keyword=capillary force kn-keyword=capillary force en-keyword=thermal energy storage density kn-keyword=thermal energy storage density en-keyword=thermal conductivity kn-keyword=thermal conductivity END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=2 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of temperature cycles on the sleep-like state in Hydra vulgaris en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Sleep is a conserved physiological phenomenon across species. It is mainly controlled by two processes: a circadian clock that regulates the timing of sleep and a homeostat that regulates the sleep drive. Even cnidarians, such as Hydra and jellyfish, which lack a brain, display sleep-like states. However, the manner in which environmental cues affect sleep-like states in these organisms remains unknown. In the present study, we investigated the effects of light and temperature cycles on the sleep-like state in Hydra vulgaris.
Results Our findings indicate that Hydra responds to temperature cycles with a difference of up to 5‹ C, resulting in decreased sleep duration under light conditions and increased sleep duration in dark conditions. Furthermore, our results reveal that Hydra prioritizes temperature changes over light as an environmental cue. Additionally, our body resection experiments show tissue-specific responsiveness in the generation ofthe sleep-like state under different environmental cues. Specifically, the upper body can generate the sleep-like state in response to a single environmental cue. In contrast, the lower body did not respond to 12-h light?dark cycles at a constant temperature.
Conclusions These findings indicate that both light and temperature influence the regulation of the sleep-like state in Hydra. Moreover, these observations highlight the existence of distinct regulatory mechanisms that govern patterns of the sleep-like state in brainless organisms, suggesting the potential involvement of specific regions for responsiveness of environmental cues for regulation of the sleep-like state. en-copyright= kn-copyright= en-aut-name=SatoAya en-aut-sei=Sato en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SekiguchiManabu en-aut-sei=Sekiguchi en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakadaKoga en-aut-sei=Nakada en-aut-mei=Koga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItohTaichi Q. en-aut-sei=Itoh en-aut-mei=Taichi Q. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Faculty of Arts and Science, Kyushu 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 Systems Life Sciences, Kyushu University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Arts and Science, Kyushu University kn-affil= en-keyword=Hydra kn-keyword=Hydra en-keyword=Sleep kn-keyword=Sleep en-keyword=Temperature kn-keyword=Temperature en-keyword=Environmental cues kn-keyword=Environmental cues END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=10819 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster en-subtitle= kn-subtitle= en-abstract= kn-abstract=Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a high-protein diet (HPD), is vital for suppressing overconsumption of protein. Gut-derived CCHa1 is received by a small subset of enteric neurons that produce short neuropeptide F, thereby modulating protein-specific satiety. Importantly, impairment of the CCHa1-mediated gut-enteric neuronal axis results in ammonia accumulation and a shortened lifespan under HPD conditions. Collectively, our findings unravel the crosstalk of gut hormone and neuronal pathways that orchestrate physiological responses to prevent and adapt to dietary protein overload. en-copyright= kn-copyright= en-aut-name=YoshinariYuto en-aut-sei=Yoshinari en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraTakashi en-aut-sei=Nishimura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoShu en-aut-sei=Kondo en-aut-mei=Shu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanimotoHiromu en-aut-sei=Tanimoto en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiTomoe en-aut-sei=Kobayashi en-aut-mei=Tomoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuyamaMakoto en-aut-sei=Matsuyama en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NiwaRyusuke en-aut-sei=Niwa en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=2 en-affil=Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=5 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=6 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=7 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=8 en-affil=Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba kn-affil= END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=7 article-no= start-page=1073 end-page=1082 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250520 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Direct insertion of an ion channel immobilized on a soft agarose gel bead into a lipid bilayer: an optimized method en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this paper, we report the development of a device that improves the conventional artificial lipid bilayer method and can measure channel currents more efficiently. Ion channel proteins are an attractive research target in biophysics, because their functions can be measured at the single-molecule level with high time resolution. In addition, they have attracted attention as targets for drug discovery because of their crucial roles in vivo. Although electrophysiological methods are powerful tools for studying channel proteins, they suffer from low measurement efficiency and require considerable skill. In our previous paper, we reported that by immobilizing channel proteins on agarose gel beads and forming an artificial lipid bilayer on the bead surface, we simultaneously solved two problems that had been hindering the efficiency of the artificial bilayer method: the time-consuming formation of artificial lipid bilayers and the time-consuming incorporation of channels into artificial bilayers. Previous studies have utilized crosslinked hard beads; however, here we show that channel current measurement can be achieved more simply and efficiently using non-crosslinked soft beads. In this study, we detailed the process of immobilizing channel proteins on the surface of non-crosslinked beads through chemical modification, allowing us to measure their channel activity. This method enables current measurements without the need for stringent bead size selection or high negative pressure. en-copyright= kn-copyright= en-aut-name=AsakuraMami en-aut-sei=Asakura en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangShuyan en-aut-sei=Wang en-aut-mei=Shuyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiranoMinako en-aut-sei=Hirano en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IdeToru en-aut-sei=Ide en-aut-mei=Toru 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=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= en-keyword=Ion channel kn-keyword=Ion channel en-keyword=Artificial lipid bilayer kn-keyword=Artificial lipid bilayer en-keyword=Suction fixation kn-keyword=Suction fixation en-keyword=Soft agarose bead kn-keyword=Soft agarose bead en-keyword=Current recording kn-keyword=Current recording END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=5 article-no= start-page=489 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=Mutagenesis Targeting the S153 Residue Within the Transmembrane ƒÀ-Hairpin of Mosquito-Larvicidal Mpp46Ab Affects Its Toxicity and the Synergistic Toxicity with Cry4Aa en-subtitle= kn-subtitle= en-abstract= kn-abstract=We constructed a library of Mpp46Ab mutants, in which S153 within the transmembrane ƒÀ-hairpin was randomly replaced by other amino acids. Mutagenesis and subsequent primary screening yielded 10 different Mpp46Ab mutants in addition to the wild type. Remarkably, S153 was replaced with a more hydrophobic amino acid in most of the mutants, and the S153I mutant in particular exhibited significantly increased toxicity. Electrophysiologic analysis using artificial lipid bilayers revealed that the single-channel conductance and PK/PCl permeability ratio were significantly increased for S153I pores. This suggests that the formation of highly ion-permeable and highly cation-selective toxin pores increases the influx of cations and water into cells, thereby facilitating osmotic shock. In addition, the S153F, S153L, and S153I mutants exhibited significantly reduced synergistic toxicity with Cry4Aa. Electrophysiologic analysis showed that the S153F, S153L, and S153I mutants form toxin pores with a significantly reduced PK/PNa permeability ratio and a significantly increased PK/PCa permeability ratio compared to wild-type pores. Thus, our results suggest that pore formation is central to the insecticidal activity of Mpp46Ab and that the ion permeability of toxin pores is a potential indicator correlated with both toxicity and synergistic toxicity with other toxins. en-copyright= kn-copyright= en-aut-name=HayakawaTohru en-aut-sei=Hayakawa en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaokaSyun en-aut-sei=Yamaoka en-aut-mei=Syun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsakuraMami en-aut-sei=Asakura en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiranoMinako en-aut-sei=Hirano en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IdeToru en-aut-sei=Ide en-aut-mei=Toru 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=Bacillus thuringiensis kn-keyword=Bacillus thuringiensis en-keyword=mosquito-larvicidal proteins kn-keyword=mosquito-larvicidal proteins en-keyword=synergistic toxicity kn-keyword=synergistic toxicity en-keyword=Culex pipiens mosquito larvae kn-keyword=Culex pipiens mosquito larvae en-keyword=side-directed mutagenesis kn-keyword=side-directed mutagenesis en-keyword=electrophysiologic analysis kn-keyword=electrophysiologic analysis END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=18 article-no= start-page=2413456 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=Cryo-EM Analysis of a Tri-Heme Cytochrome-Associated RC-LH1 Complex from the Marine Photoheterotrophic Bacterium Dinoroseobacter Shibae en-subtitle= kn-subtitle= en-abstract= kn-abstract=The reaction center-light harvesting 1 (RC-LH1) complex converts solar energy into electrical energy, driving the initiation of photosynthesis. The authors present a cryo-electron microscopy structure of the RC-LH1 isolated from a marine photoheterotrophic bacterium Dinoroseobacter shibae. The RC comprises four subunits, including a three-heme cytochrome (Cyt) c protein, and is surrounded by a closed LH ring composed of 17 pairs of antenna subunits. Notably, a novel subunit with an N-terminal ghelix-turn-helixh motif embedded in the gap between the RC and the LH ring is identified. The purified RC-LH1 complex exhibits high stability in solutions containing Mg2+ or Ca2+. The periplasmic Cyt c2 is predicted to bind at the junction between the Cyt subunit and the membrane plane, enabling electron transfer from Cyt c2 to the proximal heme of the tri-heme Cyt, and subsequently to the special pair of bacteriochlorophylls. These findings provide structural insights into the efficient energy and electron transfer processes within a distinct type of RC-LH1, and shed light on evolutionary adaptations of photosynthesis. en-copyright= kn-copyright= en-aut-name=WangWeiwei en-aut-sei=Wang en-aut-mei=Weiwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiuYanting en-aut-sei=Liu en-aut-mei=Yanting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GuJiayi en-aut-sei=Gu en-aut-mei=Jiayi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AnShaoya en-aut-sei=An en-aut-mei=Shaoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaCheng en-aut-sei=Ma en-aut-mei=Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GaoHaichun en-aut-sei=Gao en-aut-mei=Haichun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=JiaoNianzhi en-aut-sei=Jiao en-aut-mei=Nianzhi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=BeattyJohn Thomas en-aut-sei=Beatty en-aut-mei=John Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Kobl??ekMichal en-aut-sei=Kobl??ek en-aut-mei=Michal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ZhangXing en-aut-sei=Zhang en-aut-mei=Xing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ZhengQiang en-aut-sei=Zheng en-aut-mei=Qiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ChenJing]Hua en-aut-sei=Chen en-aut-mei=Jing]Hua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=College of Life Sciences, Zhejiang University kn-affil= affil-num=2 en-affil=State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University kn-affil= affil-num=3 en-affil=College of Life Sciences, Zhejiang University kn-affil= affil-num=4 en-affil=Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine kn-affil= affil-num=5 en-affil=Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine kn-affil= affil-num=6 en-affil=College of Life Sciences, Zhejiang University kn-affil= affil-num=7 en-affil=State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Department of Microbiology & Immunology, University of British Columbia kn-affil= affil-num=10 en-affil=Laboratory of Anoxygenic Phototrophs, Institute of Microbiology, Czech Academy of Science kn-affil= affil-num=11 en-affil=Department of Pathology of Sir Run Run Shaw Hospital, Department of Biophysics, Zhejiang University School of Medicine kn-affil= affil-num=12 en-affil=State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University kn-affil= affil-num=13 en-affil=College of Life Sciences, Zhejiang University kn-affil= en-keyword=energy transfer kn-keyword=energy transfer en-keyword=photoheterotrophic bacteria kn-keyword=photoheterotrophic bacteria en-keyword=photosynthesis kn-keyword=photosynthesis en-keyword=reaction center kn-keyword=reaction center en-keyword=structure kn-keyword=structure 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=20250710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurotransmitter and Receptor Mapping in Drosophila Circadian Clock Neurons via T2A-GAL4 Screening en-subtitle= kn-subtitle= en-abstract= kn-abstract=The circadian neuronal network in the brain comprises central pacemaker neurons and associated input and output pathways. These components work together to generate coherent rhythmicity, synchronize with environmental time cues, and convey circadian information to downstream neurons that regulate behaviors such as the sleep/wake cycle. To mediate these functions, neurotransmitters and neuromodulators play essential roles in transmitting and modulating signals between neurons. In Drosophila melanogaster, approximately 240 brain neurons function as clock neurons. Previous studies have identified several neurotransmitters and neuromodulators, including the Pigment-dispersing factor (PDF) neuropeptide, along with their corresponding receptors in clock neurons. However, our understanding of the neurotransmitters and receptors involved in the circadian system remains incomplete. In this study, we conducted a T2A-GAL4-based screening for neurotransmitter and receptor genes expressed in clock neurons. We identified 2 neurotransmitter-related genes and 22 receptor genes. Notably, while previous studies had reported the expression of 6 neuropeptide receptor genes in large ventrolateral neurons (l-LNv), we also found that 14 receptor genes?including those for dopamine, serotonin, and ƒÁ-aminobutyric acid?are expressed in l-LNv neurons. These findings suggest that l-LNv neurons serve as key integrative hubs within the circadian network, receiving diverse external signals. en-copyright= kn-copyright= en-aut-name=FukudaAyumi en-aut-sei=Fukuda en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoAika en-aut-sei=Saito en-aut-mei=Aika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi 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=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= en-keyword=clock neurons kn-keyword=clock neurons en-keyword=neurotransmitter kn-keyword=neurotransmitter en-keyword=T2A-GAL4 kn-keyword=T2A-GAL4 en-keyword=immunostaining kn-keyword=immunostaining en-keyword=Drosophila kn-keyword=Drosophila 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=20250418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Innovations in paper-based analytical devices and portable absorption photometers for onsite analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Two types of analytical instruments and devices?one sophisticated high-performance instrument and another portable device?have been the focus of recent trends in analytical science. The necessity of point-of-care testing and onsite analysis has accelerated the advancement of high-performance, user-friendly portable analytical devices such as paper-based analytical devices (PADs) and light-emitting diode-based portable photometers. In this review, we summarize our achievements in the study of PADs and portable photometers. Several types of PADs are capable of performing titrations, metal ion analysis, and food analysis, while photometers, which consist of paired emitter?detector light-emitting diode (PEDD) photometers, are used for thiocyanate and herbicide analysis. These PADs and photometers permit the onsite determination of real environmental, body fluid, and food samples when an equipped laboratory is unavailable. en-copyright= kn-copyright= en-aut-name=SeetasangSasikarn en-aut-sei=Seetasang en-aut-mei=Sasikarn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UmedaMika I. en-aut-sei=Umeda en-aut-mei=Mika I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RenJianchao en-aut-sei=Ren en-aut-mei=Jianchao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanetaTakashi en-aut-sei=Kaneta en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Chemistry, Faculty of Science and Technology, Thammasat University kn-affil= affil-num=2 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=4 en-affil=Department of Chemistry, Okayama University kn-affil= en-keyword=Point-of-care testing kn-keyword=Point-of-care testing en-keyword=Onsite analysis kn-keyword=Onsite analysis en-keyword=Paper-based analytical device kn-keyword=Paper-based analytical device en-keyword=Paired emitter?detector light-emitting diode kn-keyword=Paired emitter?detector light-emitting diode en-keyword=Photometer kn-keyword=Photometer en-keyword=Environmental analysis kn-keyword=Environmental analysis en-keyword=Food analysis kn-keyword=Food analysis END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=12 article-no= start-page=2916 end-page=2926.e3 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=Oxytocin facilitates human touch-induced play behavior in rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pleasant touch sensations play a fundamental role in social bonding, yet the neural mechanisms underlying affinity-like behaviors remain poorly understood. Here, we demonstrate that juvenile-adolescent rats, which naturally engage in social play with peers characterized by rough-and-tumble interactions and 50 kHz ultrasonic vocalizations indicating pleasant sensations, develop a strong affinity for human hands through similar playful contact achieved by repeated tickling with human hands. Using this rat with tickling-induced high affinity for human hands, we discovered that repeated tickling mimicking rough-and-tumble play led to increased oxytocin receptor (OTR) expression in the ventrolateral part of the ventromedial hypothalamus (VMHvl). Inhibition of oxytocin signaling in the VMHvl reduced affinity-like behaviors from rats to human hands. These findings suggest that OTR neurons in VMHvl play an important role in the increase in affinity for human hands induced by pleasant touch sensation with human touch-induced play behavior. Based on retrograde and anterograde tracing studies examining the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) as primary sources of oxytocin, we demonstrate that a subset of oxytocin fibers in the VMHvl originate from the SON, suggesting that affinity-like behavior from rats to human hands may be controlled by oxytocin signaling from magnocellular neurons. Together, this work advances our understanding of how oxytocin shapes social behavior and may inform the development of therapeutic strategies to promote positive social interactions. en-copyright= kn-copyright= en-aut-name=HayashiHimeka en-aut-sei=Hayashi en-aut-mei=Himeka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TateishiSayaka en-aut-sei=Tateishi en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InutsukaAyumu en-aut-sei=Inutsuka en-aut-mei=Ayumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaejimaSho en-aut-sei=Maejima en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HagiwaraDaisuke en-aut-sei=Hagiwara en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakumaYasuo en-aut-sei=Sakuma en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OnakaTatsushi en-aut-sei=Onaka en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GrinevichValery en-aut-sei=Grinevich en-aut-mei=Valery kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University, kn-affil= affil-num=2 en-affil=Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University kn-affil= affil-num=4 en-affil=Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, German Center for Psychiatry (DZPG), Medical Faculty Mannheim, University of Heidelberg kn-affil= affil-num=6 en-affil=Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Nippon Medical School kn-affil= affil-num=7 en-affil=Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University kn-affil= affil-num=8 en-affil=Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, German Center for Psychiatry (DZPG), Medical Faculty Mannheim, University of Heidelberg kn-affil= affil-num=9 en-affil=Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University, kn-affil= en-keyword=tickling kn-keyword=tickling en-keyword=oxytocin kn-keyword=oxytocin en-keyword=oxytocin receptor kn-keyword=oxytocin receptor en-keyword=ventrolateral part of the ventromedial hypothalamus kn-keyword=ventrolateral part of the ventromedial hypothalamus en-keyword=affinity-like behaviors kn-keyword=affinity-like behaviors END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=100242 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=Photochemical internalization of mRNA using a photosensitizer and nucleic acid carriers en-subtitle= kn-subtitle= en-abstract= kn-abstract=mRNA has great potential for therapeutic applications because it can encode a variety of proteins and antigens, in addition to advantages over DNA in terms of gene expression without genomic integration, nuclear localization, or transcription. However, therapeutic applications of mRNA require safe and effective delivery into target cells. Therefore, we aimed to investigate photochemical internalization (PCI) as a promising strategy for delivering mRNA to target cells. In this strategy, mRNA is taken up into cells by endocytosis, accumulates in endosomes, and is released in a light-dependent manner from the endosomes using an endosome-accumulating photosensitizer, aluminum phthalocyanine disulfonate (AlPcS2a), in combination with nucleic acid carrier molecules. We compared the efficacy of various nucleic acid carriers, including branched polyethyleneimine (bPEI) and poly{N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} (PAsp(DET)) under the same conditions for PCI-based mRNA delivery. Our results indicated that bPEI and PAsp(DET) at low N/P ratios exhibited efficient light-enhancement of mRNA expression by PCI with AlPcS2a. Notably, bPEI exhibited the highest light-dependent mRNA delivery among the carriers evaluated (including cationic polymers, cationic peptides, and lipids), whereas PAsp(DET) showed promise for clinical use because of its lower toxicity compared with bPEI. This PCI strategy allows effective cytosolic mRNA delivery at low N/P ratios, thereby reducing cationic carrier molecule-induced cytotoxicity. This method allows spatiotemporal control of protein expression and holds potential for novel light-dependent mRNA therapies. Overall, this study provided valuable insights into optimizing mRNA delivery systems for therapeutic applications. en-copyright= kn-copyright= en-aut-name=MaemotoHayaki en-aut-sei=Maemoto en-aut-mei=Hayaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzakiRyohei en-aut-sei=Suzaki en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=ItakaKeiji en-aut-sei=Itaka en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=mRNA kn-keyword=mRNA en-keyword=Photochemical internalization kn-keyword=Photochemical internalization en-keyword=Photosensitizer kn-keyword=Photosensitizer END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=4 article-no= start-page=329 end-page=334 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficient single-channel current measurements of the human BK channel using a liposome-immobilized gold probe en-subtitle= kn-subtitle= en-abstract= kn-abstract=The human BK channel (hBK) is an essential membrane protein that regulates various biological functions, and its dysfunction leads to serious diseases. Understanding the biophysical properties of hBK channels is crucial for drug development. Artificial lipid bilayer recording is used to measure biophysical properties at the single-channel level. However, this technique is time-consuming and complicated; thus, its measurement efficiency is very low. Previously, we developed a novel technique to improve the measurement efficiency by rapidly forming lipid bilayer membranes and incorporating ion channels into the membrane using a hydrophilically modified gold probe. To further improve our technique for application to the hBK channel, we combined it using the gold probe with a liposome fusion method. Using a probe on which liposomes containing hBK channels were immobilized, the channels were efficiently incorporated into the lipid bilayer membrane, and the measured channel currents showed the current characteristics of the hBK channel. This technique will be useful for the efficient measurements of the channel properties of hBK and other biologically important channels. en-copyright= kn-copyright= en-aut-name=HiranoMinako en-aut-sei=Hirano en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsakuraMami en-aut-sei=Asakura en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IdeToru en-aut-sei=Ide en-aut-mei=Toru 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= en-keyword=Human BK channel kn-keyword=Human BK channel en-keyword=Artificial lipid bilayer recording kn-keyword=Artificial lipid bilayer recording en-keyword=Ion channel current kn-keyword=Ion channel current en-keyword=Single-channel recording kn-keyword=Single-channel recording END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=311 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Co-occurrence of interstitial lung disease and pulmonary embolism as adverse events of adjuvant osimertinib treatment for EGFR mutant non-small cell lung cancer: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Postoperative osimertinib for EGFR mutant non-small cell lung cancer has become the standard of care. However, its adverse events in clinical practice remain unclear. We report a case of interstitial lung disease and pulmonary embolism occurring simultaneously as adverse events during adjuvant osimertinib treatment.
Case presentation A 74-year-old woman, diagnosed with left lower lobe lung adenocarcinoma harboring an EGFR mutation, underwent a left lower lobectomy with lymph node dissection. During adjuvant osimertinib therapy, the patient developed respiratory distress with hypoxia, leading to the diagnosis of interstitial lung disease. Despite immediate steroid therapy, respiratory distress persisted, the patient developed leg edema. She was diagnosed with deep vein thrombosis and pulmonary embolism via contrast-enhanced computed tomography scan. Following treatment with steroid and anticoagulation, her clinical symptoms improved rapidly, and she showed no recurrence of interstitial lung disease, pulmonary embolism, or lung cancer over the following nine months.
Conclusions We encountered a case of interstitial lung disease and pulmonary embolism occurring simultaneously as adverse events during adjuvant osimertinib treatment. In patients with osimertinib-induced interstitial lung disease, particularly when respiratory symptoms show poor improvement with steroid treatment, the possibility of pulmonary embolism complications should be suspected. en-copyright= kn-copyright= en-aut-name=ManabeKenta en-aut-sei=Manabe en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=FurukawaShinichi en-aut-sei=Furukawa en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SenoTomoya en-aut-sei=Seno en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshimuraKousei en-aut-sei=Ishimura en-aut-mei=Kousei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=Osimertinib kn-keyword=Osimertinib en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Interstitial lung disease kn-keyword=Interstitial lung disease en-keyword=Pulmonary embolism kn-keyword=Pulmonary embolism END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=7 article-no= start-page=808 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Carnosol, a Rosemary Ingredient Discovered in a Screen for Inhibitors of SARM1-NAD+ Cleavage Activity, Ameliorates Symptoms of Peripheral Neuropathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD+) hydrolase involved in axonal degeneration and neuronal cell death. SARM1 plays a pivotal role in triggering the neurodegenerative processes that underlie peripheral neuropathies, traumatic brain injury, and neurodegenerative diseases. Importantly, SARM1 knockdown or knockout prevents the degeneration; as a result, SARM1 has been attracting attention as a potent therapeutic target. In recent years, the development of several SARM1 inhibitors derived from synthetic chemical compounds has been reported; however, no dietary ingredients with SARM1 inhibitory activity have been identified. Therefore, we here focused on dietary ingredients and found that carnosol, an antioxidant contained in rosemary, inhibits the NAD+-cleavage activity of SARM1. Purified carnosol inhibited the enzymatic activity of SARM1 and suppressed neurite degeneration and cell death induced by the anti-cancer medicine vincristine (VCR). Carnosol also inhibited VCR-induced hyperalgesia symptoms, suppressed the loss of intra-epidermal nerve fibers in vivo, and reduced the blood fluid level of phosphorylated neurofilament-H caused by an axonal degeneration event. These results indicate that carnosol has a neuroprotective effect via SARM1 inhibition in addition to its previously known antioxidant effect via NF-E2-related factor 2 and thus suppresses neurotoxin-induced peripheral neuropathy. en-copyright= kn-copyright= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgawaKazuki en-aut-sei=Ogawa en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiYu en-aut-sei=Yasui en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OchiToshiki en-aut-sei=Ochi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoKen-Ichi en-aut-sei=Yamamoto en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=WadaYoji en-aut-sei=Wada en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraHiromichi en-aut-sei=Nakamura en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Tama Biochemical Co., Ltd. kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Tama Biochemical Co., Ltd. kn-affil= affil-num=9 en-affil=Tama Biochemical Co., Ltd. kn-affil= affil-num=10 en-affil=Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=SARM1 kn-keyword=SARM1 en-keyword=carnosol kn-keyword=carnosol en-keyword=NAD+ kn-keyword=NAD+ en-keyword=axon degeneration kn-keyword=axon degeneration en-keyword=peripheral neuropathy kn-keyword=peripheral neuropathy END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=3 article-no= start-page=152 end-page=161 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=Osteogenesis imperfecta: pathogenesis, classification, and treatment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteogenesis imperfecta (OI) is a congenital skeletal disorder characterized by varying degrees of bone fragility and deformities. Extraskeletal manifestations, such as blue sclera, dentinogenesis imperfecta, growth disturbance, hearing impairment, and muscle weakness, occasionally accompany OI. Many genes have been identified as causative of OI, such as the type I collagen gene and genes involved in the folding, processing, and crosslinking of type I collagen molecules, osteoblast differentiation, and bone mineralization. According to the discovery of the causative gene of OI, nosology and classifications have also been revised and the gdyadic approachh based nomenclature according to the severity and each causative gene of OI was recently adopted. Intravenous or oral bisphosphonates have been administered to treat bone fragility in children with OI and a reduction in the frequency of bone fractures has been reported. However, despite the increase of bone mineral density, evidence of bone fracture prevention is limited. Recently, excessive transforming growth factor ƒÀ signaling pathway and excessive endoplasmic reticulum stress have been reported as the pathogenesis of OI, and treatment strategies based on these pathogeneses have been developed. This review summarizes the molecular basis, transition of nosology and classification, status of bisphosphonate therapy, and development of treatment strategies. 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= affil-num=1 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= en-keyword=fracture kn-keyword=fracture en-keyword=child kn-keyword=child en-keyword=bisphosphonate kn-keyword=bisphosphonate en-keyword=classification kn-keyword=classification en-keyword=treatment kn-keyword=treatment END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=3 article-no= start-page=321 end-page=343 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=Physiological and Biochemical Traits of Dormancy Release and Growth Resumption in Japanese Cedar in the Warm-Temperate Zone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Global warming will disturb dormancy release and growth resumption of trees. To better understand this process, it is important to investigate physiological and biochemical traits related to these stages. We examined dormancy release and growth resumption in Japanese cedar (Cryptomeria japonica [L.] D. Don), an evergreen needle-leaved tree, in the warm-temperate zone by evaluating budbreak under growth-promoting conditions, and simultaneously examining respiration rates and contents of carbohydrates and phytohormones in shoots from November 2022 to March 2023. A long time to budbreak and the lowest budbreak rates of 75% in November indicated shallow dormancy. Budbreak rates of 98%, short time to budbreak, and first appearance of budbreak in the field in March indicated growth resumption. Continuous changes in budbreak rates and time to budbreak between dormancy and growth resumption indicated dormancy was gradually released. Surges in budbreak rates in December indicated dormancy was almost completely released by early winter. Contents of abscisic acid (ABA) and salicylic acid (SA) decreased from November, remained low in March, and were strongly associated with budbreak rates according to principal component analysis. It was suggested that the depletion of SA led to the depletion of ABA, contributing to dormancy release and growth resumption. Fructose and trans-zeatin accumulated until February, and low levels of starch, indole-3-acetic acid, jasmonic acid, and jasmonic acid-isoleucine during winter was followed by accumulation in March. Although these biochemical traits were less related to budbreak rates compared to ABA and SA, they seemed to assist either dormancy release or growth resumption. en-copyright= kn-copyright= en-aut-name=HiejimaShoma en-aut-sei=Hiejima en-aut-mei=Shoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SeinoHiroto en-aut-sei=Seino en-aut-mei=Hiroto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HachisukaRico en-aut-sei=Hachisuka en-aut-mei=Rico kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeYuka en-aut-sei=Watanabe en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuuraTakakazu en-aut-sei=Matsuura en-aut-mei=Takakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UgawaShin en-aut-sei=Ugawa en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=The United Graduate School of Agricultural Sciences, Kagoshima University kn-affil= affil-num=2 en-affil=Graduate School of Agriculture, Forestry and Fisheries, Kagoshima University kn-affil= affil-num=3 en-affil=The United Graduate School of Agricultural Sciences, Kagoshima University kn-affil= affil-num=4 en-affil=Graduate School of Agriculture, Forestry and Fisheries, Kagoshima University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=The United Graduate School of Agricultural Sciences, Kagoshima University kn-affil= en-keyword=Japanese cedar kn-keyword=Japanese cedar en-keyword=Warm-temperate zone kn-keyword=Warm-temperate zone en-keyword=Dormancy release kn-keyword=Dormancy release en-keyword=Growth resumption kn-keyword=Growth resumption en-keyword=Physio-biochemical traits kn-keyword=Physio-biochemical traits END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=10 article-no= start-page=1692 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Characteristics of Vitamin D Deficiency Detected in Long COVID Patients During the Omicron Phase en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: To characterize the clinical significance of vitamin D deficiency (VDD) detected in long COVID, a retrospective observational study was performed for outpatients who visited our clinic during the period from May 2024 to November 2024. Methods: Clinical trends in long COVID patients diagnosed with VDD who showed serum concentrations of 25-hydroxyvitamin D (25-OHD) lower than 20 ng/mL were compared with those in long COVID patients in a non-deficient vitamin D (NDD) group. Results: Of 126 patients with long COVID, 97 patients (female: 50) who had been infected during the Omicron phase were included. Sixty-six patients (68%) were classified in the VDD group. The median serum concentrations of 25-OHD were 14.8 ng/mL in the VDD group and 22.9 ng/mL in the NDD group. There were no significant differences between the two groups in terms of age, gender, BMI, severity of COVID-19, period after infection and vaccination history. Although the levels of serum calcium and phosphate were not significantly different between the two groups, the percentages of patients in the VDD group who complained of dizziness, memory impairment, palpitation and appetite loss were larger than those in the NDD group. Of note, the patients who complained of palpitation showed significantly lower concentrations of serum 25-OHD than those in the patients without palpitation (median: 11.9 vs. 17.3 ng/mL). Moreover, patients in the VDD group had significantly higher scores for physical and mental fatigue as well as higher scores for depressive symptoms. Conclusions: Collectively, VDD is involved in clinical manifestations of long COVID, particularly symptoms of palpitation, fatigue and depression. en-copyright= kn-copyright= en-aut-name=MatsudaYui en-aut-sei=Matsuda en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 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=6 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=7 ORCID= en-aut-name=YokotaYuya en-aut-sei=Yokota en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=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= en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=25-hydroxyvitamin D kn-keyword=25-hydroxyvitamin D en-keyword=long COVID kn-keyword=long COVID en-keyword=palpitation kn-keyword=palpitation en-keyword=vitamin D deficiency kn-keyword=vitamin D deficiency END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=e000923 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=Reversible cerebral vasoconstriction syndrome in idiopathic multicentric Castleman disease under treatment with tocilizumab en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Idiopathic multicentric Castleman disease (iMCD) is a rare polyclonal lymphoproliferative disorder characterised by systemic inflammation resulting from overproduction of interleukin 6 (IL-6). While iMCD primarily affects the lymph nodes and related tissues, it can also rarely involve the central nervous system.
Case presentation We report the case of a 58-year-old female patient with at least a 3-year history of iMCD, who experienced acute thunderclap headaches due to reversible cerebral vasoconstriction syndrome (RCVS). RCVS occurred 3?months after initiating treatment with tocilizumab, a humanised anti-IL-6 receptor monoclonal antibody, and was accompanied by focal cortical subarachnoid haemorrhage (SAH). Elevated IL-6 levels were found in both serum and cerebrospinal fluid. MR angiography revealed multiple diffuse stenotic lesions in the bilateral middle and posterior cerebral arteries, which, along with bilateral cerebral oedema, resolved within 3?months. The diffuse nature of the cerebral vasospasm and the presence of bilateral brain oedema suggested that cerebral vasospasm was due to RCVS rather than SAH.
Conclusions In patients with Castleman disease, RCVS may occur due to IL-6-dependent chronic cerebral vascular inflammation, either as a primary condition or as a complication of tocilizumab treatment. en-copyright= kn-copyright= en-aut-name=KamimuraNaoya en-aut-sei=Kamimura en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaNaohisa en-aut-sei=Ueda en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraKatsuo en-aut-sei=Kimura en-aut-mei=Katsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=KishidaHitaru en-aut-sei=Kishida en-aut-mei=Hitaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaFumiaki en-aut-sei=Tanaka en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Neurology, Yokohama City University Medical Center kn-affil= affil-num=2 en-affil=Department of Neurology, Yokohama City University Medical Center kn-affil= affil-num=3 en-affil=Department of Neurology, Yokohama City University Medical Center kn-affil= affil-num=4 en-affil= kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Department of Neurology, Yokohama City University Medical Center kn-affil= affil-num=7 en-affil=Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=4 article-no= start-page=510 end-page=524 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250626 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=C1orf50 Drives Malignant Melanoma Progression Through the Regulation of Stemness en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Recent advancements in omics analysis have significantly enhanced our understanding of the molecular pathology of malignant melanoma, leading to the development of novel therapeutic strategies that target specific vulnerabilities within the disease. Despite these improvements, the factors contributing to the poor prognosis of patients with malignant melanoma remain incompletely understood. The aim of this study was to investigate the role of C1orf50 (Chromosome 1 open reading frame 50), a gene previously of unknown function, as a prognostic biomarker in melanoma.
Materials and Methods: We performed comprehensive transcriptome data analysis and subsequent functional validation of the human Skin Cutaneous Melanoma project from The Cancer Genome Atlas (TCGA).
Results: Elevated expression levels of C1orf50 correlated with worse survival outcomes. Mechanistically, we revealed that C1orf50 plays a significant role in the regulation of cell cycle processes and cancer cell stemness, providing a potential avenue for novel therapeutic interventions in melanoma.
Conclusion: This study is the first to identify C1orf50 as a prognostic biomarker in melanoma. The clinical relevance of our results sheds light on the importance of further investigation into the biological mechanisms underpinning C1orf50fs impact on melanoma progression and patient prognosis. en-copyright= kn-copyright= en-aut-name=OTANIYUSUKE en-aut-sei=OTANI en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MAEKAWAMASAKI en-aut-sei=MAEKAWA en-aut-mei=MASAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TANAKAATSUSHI en-aut-sei=TANAKA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PE?ATIRSO en-aut-sei=PE?A en-aut-mei=TIRSO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=ROGACHEVSKAYAANNA en-aut-sei=ROGACHEVSKAYA en-aut-mei=ANNA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TOYOOKASHINICHI en-aut-sei=TOYOOKA en-aut-mei=SHINICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ROEHRLMICHAEL H. en-aut-sei=ROEHRL en-aut-mei=MICHAEL H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FUJIMURAATSUSHI en-aut-sei=FUJIMURA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=5 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=6 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=9 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=melanoma kn-keyword=melanoma en-keyword=cancer stem cells kn-keyword=cancer stem cells en-keyword=YAP/TAZ kn-keyword=YAP/TAZ 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=20250624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dual functions of SNAP25 in mouse taste buds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Type III cells in mouse taste buds are considered to transmit aversive stimuli, such as sourness, to the gustatory nerve through vesicular synapses. Synaptosome-associated protein 25 (SNAP25) might contribute to synaptic vesicular release in sour sensation, although direct evidence has been lacking. Here, we demonstrated that epithelia-specific Snap25 conditional knockout (cKO) mice exhibited a significant reduction in the number of type III cells. Notably, the proportion of 5-ethynyl 2Œ-deoxyuridine-positive post-mitotic type III cells in Snap25 cKO mice was significantly lower on tracing day 14, but not at day 7, which suggests that SNAP25 contributes to the maintenance of type III cells. In a short-term lick test, Snap25 cKO (sour taste absent) and Snap25/ transient receptor potential vanilloid 1 double KO (sour taste and somatosensory absent) mice exhibit a significantly higher lick response to sour tastants, confirming the role of SNAP25 for sour sensation. Electrophysiological recordings of the chorda tympani nerve reveal nearly abolished ammonium and sour taste responses in Snap25 cKO mice, which concludes sour-dependent synapse transmission in type III cells. Overall, these data suggest that vesicular synapses in taste buds are indispensable for transmission of information from, and the replenishment of, sour-sensitive type III taste cells. en-copyright= kn-copyright= en-aut-name=HorieKengo en-aut-sei=Horie en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangKuanyu en-aut-sei=Wang en-aut-mei=Kuanyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangHai en-aut-sei=Huang en-aut-mei=Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasumatsuKeiko en-aut-sei=Yasumatsu en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NinomiyaYuzo en-aut-sei=Ninomiya en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Tokyo Dental Junior College kn-affil= affil-num=5 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=sour taste kn-keyword=sour taste en-keyword=synapse kn-keyword=synapse en-keyword=taste buds kn-keyword=taste buds en-keyword=taste nerve kn-keyword=taste nerve en-keyword=Type III cells kn-keyword=Type III cells END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=e86695 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Managing Persistent Pupillary Membranes With Surgery or Medication: A Report of Three Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=The persistent pupillary membrane, as a congenital anomaly, is a remnant of a network of feeding blood vessels for the lens of the eye, called tunica vasculosa lentis. This study reports three patients with persistent pupillary membrane in both eyes who presented in different situations and were managed differently to achieve better vision. The first child (Case 1) who had been seen initially at the age of two years complained of severe photophobia even though he had good visual acuity, and hence, he and his family chose surgical resection of the pupillary membrane in both eyes at the age of six years just before the admission to an elementary school. He did not develop any surgical complications, such as cataract and glaucoma, and maintained the visual acuity in decimals of 1.2 in both eyes at the age of 17 years.
The second child (Case 2), who was seen first at the age of one month, had persistent pupillary membranes in both eyes, together with Peters' anomaly in the left eye. The iris process adhesion to the corneal inner surface was visualized later by optical coherence tomography. She wore full-correction glasses and obtained the visual acuity of 0.7 in the right eye, so she had no problem studying at an elementary school. She used topical 1% atropine once a week in both eyes to maintain pupillary dilation and also used 0.5% timolol and 1% brinzolamide as pressure-lowering eye drops in the left eye with Peters' anomaly.
The third patient (Case 3) with persistent pupillary membranes in both eyes complained of vision problems for the first time at the age of 49 years when she developed cataract. Surgical resection of the pupillary membrane was done in the initial phase of cataract surgery with intraocular lens implantation in both eyes. At surgical resection of the pupillary membrane, a safe and efficient way was to cut the root of the pupillary membrane on the iris surface with scissors, and then the isolated tissues of the pupillary membrane were pulled out with forceps from the side port at the corneal limbus. Pathological examinations of the excised tissues showed blood vessels with red blood cells in the lumen. In such a rare congenital disease as the persistent pupillary membrane, a case-based approach to choose a better option in different conditions from individual to individual is still required to have a better vision in learning at school and in daily working life. 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=Division of Healthcare Science, 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=anterior segment dysgenesis kn-keyword=anterior segment dysgenesis en-keyword=cataract kn-keyword=cataract en-keyword=forceps kn-keyword=forceps en-keyword=optical coherence tomography kn-keyword=optical coherence tomography en-keyword=persistent pupillary membrane kn-keyword=persistent pupillary membrane en-keyword=peters anomaly kn-keyword=peters anomaly en-keyword=resection kn-keyword=resection en-keyword=scissors kn-keyword=scissors en-keyword=vitrectomy cutter kn-keyword=vitrectomy cutter END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=e85680 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Whole-Eye Radiation for the Local Control of Choroidal Lymphoma in Primary Central Nervous System Lymphoma: A 14-Year Case Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Involved-site radiation therapy is effective for curative and palliative treatments of cancers, including lymphoma. This case study describes the use of whole-eye radiation for primary intraocular lymphoma occurring during primary central nervous system lymphoma. The patient, a 68-year-old man, developed personality changes and apathy two weeks after cataract surgery combined with vitrectomy for vitreous opacity in the left eye. Magnetic resonance imaging revealed a mass lesion in the left frontal lobe, and biopsy by craniotomy confirmed diffuse large B-cell lymphoma. He underwent chemotherapy using rituximab combined with high-dose methotrexate and high-dose cytarabine in association with intrathecal methotrexate and cytarabine injections, leading to complete remission. At age 75, he noticed forgetfulness, and fluorodeoxyglucose positron emission tomography and magnetic resonance imaging revealed a relapse of lymphoma in the splenium of the corpus callosum. He underwent chemotherapy using rituximab combined with high-dose methotrexate, followed by monthly rituximab monotherapy for one year and then rituximab monotherapy every two months for one year. He maintained complete remission with no treatment until age 78, when he developed subretinal choroidal lesions in the left eye and underwent whole-eye radiation at 40 Gy. One year later, he developed subretinal choroidal lesions in the right eye and underwent whole-eye radiation at 40 Gy. At age 81, he had lower limb weakness with disorientation. Magnetic resonance imaging showed a relapse of lymphoma in the right frontal to temporal lobe. The brain lesions showed a marked response to four weeks of oral tirabrutinib as a salvage therapy, but the lesions regrew, and the patient died seven months later. Throughout the treatment, he maintained a visual acuity of 0.7 (decimal scale) in both eyes. In conclusion, whole-eye radiation should be considered as a treatment option for the local control of active intraocular lymphoma, especially choroidal lesions, for patients with primary central nervous system lymphoma with no active brain lesions and without systemic treatment. 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=YanoTomofumi en-aut-sei=Yano en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshioKotaro en-aut-sei=Yoshio en-aut-mei=Kotaro 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=NishimuraHirotake en-aut-sei=Nishimura en-aut-mei=Hirotake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Okayama Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University 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 Pathology, Kawasaki Medical School kn-affil= affil-num=6 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=bruton tyrosine kinase (btk) inhibitor kn-keyword=bruton tyrosine kinase (btk) inhibitor en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=diffuse large b-cell lymphoma kn-keyword=diffuse large b-cell lymphoma en-keyword=fluorodeoxyglucose positron emission tomography kn-keyword=fluorodeoxyglucose positron emission tomography 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=radiation therapy (radiotherapy) kn-keyword=radiation therapy (radiotherapy) en-keyword=tirabrutinib kn-keyword=tirabrutinib en-keyword=whole-eye radiation kn-keyword=whole-eye radiation END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=5 article-no= start-page=164 end-page=173 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nephronophthisis and Retinitis Pigmentosa (Senior-Loken Syndrome) After Living-Donor Kidney Transplantation: Twelve-Year Follow-Up in a Young Woman en-subtitle= kn-subtitle= en-abstract= kn-abstract=Senior-Loken syndrome is a hereditary ciliopathy with recessive trait that manifests as nephronophthisis and retinitis pigmentosa. This report described an 18-year-old woman who was referred to a University Hospital to set up a treatment plan for chronic renal failure of an unknown cause. She had experienced nocturnal polyurea from the age of 12 years and was found to have an elevated level of serum creatinine at 3 mg/dL at the age of 15 years. She underwent renal biopsy at a hometown regional hospital which showed global glomerulosclerosis in six of the 13 glomeruli examined, renal tubular dilation in irregular shape, and marked interstitial fibrosis with lymphocytic infiltration. At the age of 19 years, she received a living-donor kidney transplant from her 46-year-old father as a preemptive therapy. At surgery, biopsy of the fatherfs donor kidney showed two glomeruli with global sclerosis out of 24 glomeruli examined, in association with minimal interstitial fibrosis and lymphocytic infiltration. She began to have extended-release tacrolimus 4 mg daily and mycophenolate mofetil 1,000 mg daily. According to the standard protocol, she underwent biopsy of the transplanted donor kidney to reveal interstitial fibrosis and lymphocytic infiltration, in addition to no sign of rejection and no glomerular deposition of immunoglobulins and complements, both 4 weeks and 14 months after the kidney transplantation. At the age of 23 years, 4 years after the kidney transplantation, she was, for the first time, diagnosed retinitis pigmentosa, and hence, Senior-Loken syndrome. She was followed up in the stable condition with basal doses of tacrolimus 5 mg daily, mycophenolate mofetil 1,000 mg daily, and prednisolone 5 mg daily up until now in 12 years after the kidney transplantation. The interstitial fibrosis with lymphocytic infiltration in the donor kidney might be a milder presentation of the disease with recessive inheritance. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Retinitis pigmentosa kn-keyword=Retinitis pigmentosa en-keyword=Nephronophthisis kn-keyword=Nephronophthisis en-keyword=Senior-Loken syndrome kn-keyword=Senior-Loken syndrome en-keyword=Kidney transplantation kn-keyword=Kidney transplantation en-keyword=Living donor kn-keyword=Living donor en-keyword=Kidney biopsy kn-keyword=Kidney biopsy en-keyword=Pathology kn-keyword=Pathology en-keyword=Computed tomography scan kn-keyword=Computed tomography scan en-keyword=Ciliopathy kn-keyword=Ciliopathy en-keyword=Optical coherence tomography kn-keyword=Optical coherence tomography END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=e83484 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Detailed Ophthalmic and Pathological Features of Choroidal Metastasis From Breast Cancer: A Case Series of Five Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Breast cancer causes choroidal metastases on rare occasions. This study presented the eye manifestations of choroidal metastases from breast cancer and their response to treatments in detail as well as their pathological correlation in five patients. The patients' age at the diagnosis of breast cancer ranged from 24 to 69 years (median: 37 years). The time from the diagnosis of breast cancer to the detection of metastases was concurrent in one patient, two years later in three patients, and six years later in the other patient. The time from the detection of systemic metastases to the detection of choroidal metastases was the same in one patient, while it ranged from one to seven years later in four patients. Choroidal metastases were in the unilateral eye of four patients, whereas they were in both eyes of one patient. Choroidal metastases manifested as one or a few nodular or flat choroidal lesions with serous retinal detachment. As for the treatment of choroidal metastases, enucleation of the right eye was chosen based on the patient's wish as well as the family's wish in the earliest patient when cancer notification was not the norm in Japan. In the other four patients, whole-eye radiation was performed to reduce the choroidal metastatic lesions. As regards the prognosis, which was available in four patients, three patients died within one year from the diagnosis of choroidal metastases, while one patient died one year and eight months later. Regarding the pathology of breast cancer, which was available in four patients, immunostaining of the preserved enucleated eye in the earliest patient revealed that breast cancer cells in the choroidal metastatic lesion were positive for estrogen receptor and negative for progesterone receptor and human epidermal growth factor receptor 2 (HER2). Invasive ductal carcinoma in two patients was positive for estrogen receptor and negative for HER2, while invasive ductal carcinoma in the other patient was triple-negative for estrogen receptor, progesterone receptor, and HER2 with a high Ki-67 index. In conclusion, the prognosis for life was poor in patients with breast cancer who developed choroidal metastases. Choroidal metastatic lesions showed a response to whole-eye radiation to improve the quality of vision at the end of life. Vision-related symptoms should be monitored in the course of chemotherapy for systemic metastases. 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=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MuraokaAtsushi en-aut-sei=Muraoka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Healthcare Science, 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 Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=choroidal metastasis kn-keyword=choroidal metastasis en-keyword=estrogen receptor kn-keyword=estrogen receptor en-keyword=her2 kn-keyword=her2 en-keyword=immunostaining kn-keyword=immunostaining en-keyword=invasive ductal carcinoma kn-keyword=invasive ductal carcinoma en-keyword=ki-67 kn-keyword=ki-67 en-keyword=progesterone receptor kn-keyword=progesterone receptor en-keyword=radiation kn-keyword=radiation END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=6 article-no= start-page=e70126 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=Sulphur]Acquisition Pathways for Cysteine Synthesis Confer a Fitness Advantage to Bacteria in Plant Extracts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bacteria and plants are closely associated with human society, in fields such as agriculture, public health, the food industry, and waste disposal. Bacteria have evolved nutrient-utilisation systems adapted to achieve the most efficient growth in their major habitats. However, empirical evidence to support the significance of bacterial nutrient utilisation in adaptation to plants is limited. Therefore, we investigated the genetic and nutritional factors required for bacterial growth in plant extracts by screening an Escherichia coli gene-knockout library in vegetable-based medium. Mutants lacking genes involved in sulphur assimilation, whereby sulphur is transferred from sulphate to cysteine, exhibited negligible growth in vegetable-based medium or plant extracts, owing to the low cysteine levels. The reverse transsulphuration pathway from methionine, another pathway for donating sulphur to cysteine, occurring in bacteria such as Bacillus subtilis, also played an important role in growth in plant extracts. These two sulphur-assimilation pathways were more frequently observed in plant-associated than in animal-associated bacteria. Sulphur-acquisition pathways for cysteine synthesis thus play a key role in bacterial growth in plant-derived environments such as plant residues and plant exudates. en-copyright= kn-copyright= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaguchiSaki en-aut-sei=Yamaguchi en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukaokaTaketo en-aut-sei=Tsukaoka en-aut-mei=Taketo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsunodaMakoto en-aut-sei=Tsunoda en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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 Pharmaceutical Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Bacillus subtilis kn-keyword=Bacillus subtilis en-keyword=bacterial nutrient utilisation kn-keyword=bacterial nutrient utilisation en-keyword=cysteine synthesis kn-keyword=cysteine synthesis en-keyword=Escherichia coli kn-keyword=Escherichia coli en-keyword=plant-derived environments kn-keyword=plant-derived environments en-keyword=sulphur acquisition pathway kn-keyword=sulphur acquisition pathway END start-ver=1.4 cd-journal=joma no-vol=227 cd-vols= no-issue= article-no= start-page=110168 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The hidden cation-selective pore in ion-conducting aquaporin OsPIP2;4 from rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ion-conducting aquaporins (icAQPs) transport ions as well as water. Although the molecular mechanism of how AQPs establish selective permeability for water molecules is well understood, the ion-transporting mechanism in icAQPs has not yet been fully elucidated. In this study, we investigated the molecular mechanism of cation transport in OsPIP2;4, an icAQP in rice, by homology modeling and the electrophysiological analysis using Xenopus laevis oocytes. Water and ion transport assays using OsPIP2;4 T227M and G278K mutants strongly suggested that water- and cation-transporting pathways are independent of each other. Data from amino acid substitutions V54I and A143G in OsPIP2;4 led to the identification of a novel hidden pathway for cation transport located on the side surfaces of the tetramer channel, where two protomers are in contact, which is distinct from conventional monomeric pores and the tetrameric central pore in AQPs. Moreover, the present results provide the possibility that this hypothetical hidden pore also functions in the barley icAQP HvPIP2;8. The overall structure of this novel pathway appears to differ from the structure of general cation channels. However, the arrangement of hydrophilic amino acids at the entrance of the pathway of OsPIP2;4 was found to be comparable to that of some cation channels, which implies that the molecular mechanism of dehydration of hydrated ions might resemble that of the channels. Although direct structural evidence is needed to confirm the proposed pathway, the present study can be a stepping stone toward unraveling the mechanism of dual water and ion transport through icAQPs in plants. en-copyright= kn-copyright= en-aut-name=OnoShuntaro en-aut-sei=Ono en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TranSen Thi Huong en-aut-sei=Tran en-aut-mei=Sen Thi Huong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitohYasunori en-aut-sei=Saitoh en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UtsugiShigeko en-aut-sei=Utsugi en-aut-mei=Shigeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HorieTomoaki en-aut-sei=Horie en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Rice kn-keyword=Rice en-keyword=Barley kn-keyword=Barley en-keyword=Ion transport kn-keyword=Ion transport en-keyword=Ion-conducting aquaporin (icAQP) kn-keyword=Ion-conducting aquaporin (icAQP) en-keyword=Plasma membrane intrinsic protein (PIP) kn-keyword=Plasma membrane intrinsic protein (PIP) END start-ver=1.4 cd-journal=joma no-vol=301 cd-vols= no-issue=7 article-no= start-page=110291 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=A repertoire of visible light?sensitive opsins in the deep-sea hydrothermal vent shrimp Rimicaris hybisae en-subtitle= kn-subtitle= en-abstract= kn-abstract=Unlike terrestrial environments, where humans reside, there is no sunlight in the deep sea. Instead, dim visible light from black-body radiation and bioluminescence illuminates hydrothermal vent areas in the deep sea. A deep-sea hydrothermal vent shrimp, Rimicaris hybisae, is thought to detect this dim light using its enlarged dorsal eye; however, the molecular basis of its photoreception remains unexplored. Here, we characterized the molecular properties of opsins, universal photoreceptive proteins in animals, found in R. hybisae. Transcriptomic analysis identified six opsins: three Gq-coupled opsins, one Opn3, one Opn5, and one peropsin. Functional analysis revealed that five of these opsins exhibited light-dependent G protein activity, whereas peropsin exhibited the ability to convert all-trans-retinal to 11-cis-retinal like photoisomerases. Notably, all the R. hybisae opsins, including Opn5, convergently show visible light sensitivity (around 457?517 nm), whereas most opsins categorized as Opn5 have been demonstrated to be UV sensitive. Mutational analysis revealed that the unique visible light sensitivity of R. hybisae Opn5 is achieved through the stabilization of a protonated Schiff base by a counterion residue at position 83 (Asp83), which differs from the position identified in other opsins. These findings suggest that the vent shrimp R. hybisae has adapted its photoreceptive devices to dim deep-sea hydrothermal light by selectively maintaining a repertoire of visible light?sensitive opsins, including the uniquely tuned Opn5. en-copyright= kn-copyright= en-aut-name=NagataYuya en-aut-sei=Nagata en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyamotoNorio en-aut-sei=Miyamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoKeita en-aut-sei=Sato en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraYosuke en-aut-sei=Nishimura en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniokaYuki en-aut-sei=Tanioka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamanakaYuji en-aut-sei=Yamanaka en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=TakahashiKuto en-aut-sei=Takahashi en-aut-mei=Kuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ObayashiKohei en-aut-sei=Obayashi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsukamotoHisao en-aut-sei=Tsukamoto en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakaiKen en-aut-sei=Takai en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamashitaTakahiro en-aut-sei=Yamashita en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Institute for Extra-Cutting-Edge Science and Technology Avant-Garde Research (X-Star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Research Center for Bioscience and Nanoscience (CeBN), Research Institute for Marine Resources Utilization, Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=5 en-affil=School of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=School of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=8 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Biology, Graduate School of Science, Kobe University kn-affil= affil-num=10 en-affil=Department of Biology, Graduate School of Science, Kobe University kn-affil= affil-num=11 en-affil=Institute for Extra-Cutting-Edge Science and Technology Avant-Garde Research (X-Star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=12 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Biophysics, Graduate School of Science, Kyoto University kn-affil= affil-num=14 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=rhodopsin kn-keyword=rhodopsin en-keyword=opsin kn-keyword=opsin en-keyword=G protein?coupled receptor kn-keyword=G protein?coupled receptor en-keyword=signal transduction kn-keyword=signal transduction en-keyword=photoreceptor kn-keyword=photoreceptor en-keyword=vision kn-keyword=vision en-keyword=photobiology kn-keyword=photobiology en-keyword=vent shrimp kn-keyword=vent shrimp en-keyword=deep sea kn-keyword=deep sea en-keyword=molecular evolution kn-keyword=molecular evolution 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=20250620 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=International Consensus Histopathological Criteria for Subtyping Idiopathic Multicentric Castleman Disease Based on Machine Learning Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder classified into three recognized clinical subtypes?idiopathic plasmacytic lymphadenopathy (IPL), TAFRO, and NOS. Although clinical criteria are available for subtyping, diagnostically challenging cases with overlapping histopathological features highlight the need for an improved classification system integrating clinical and histopathological findings. We aimed to develop an objective histopathological subtyping system for iMCD that closely correlates with the clinical subtypes. Excisional lymph node specimens from 94 Japanese iMCD patients (54 IPL, 28 TAFRO, 12 NOS) were analyzed for five key histopathological parameters: germinal center (GC) status, plasmacytosis, vascularity, hemosiderin deposition, and gwhirlpoolh vessel formation in GC. Using hierarchical clustering, we visualized subgroups and developed a machine learning-based decision tree to differentiate the clinical subtypes and validated it in an external cohort of 12 patients with iMCD. Hierarchical cluster analysis separated the IPL and TAFRO cases into mutually exclusive clusters, whereas the NOS cases were interspersed between them. Decision tree modeling identified plasmacytosis, vascularity, and whirlpool vessel formation as key features distinguishing IPL from TAFRO, achieving 91% and 92% accuracy in the training and test sets, respectively. External validation correctly classified all IPL and TAFRO cases, confirming the reproducibility of the system. Our histopathological classification system closely aligns with the clinical subtypes, offering a more precise approach to iMCD subtyping. It may enhance diagnostic accuracy, guide clinical decision-making for predicting treatment response in challenging cases, and improve patient selection for future research. Further validation of its versatility and clinical utility is required. 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=HaratakeTomoka en-aut-sei=Haratake en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=SumiyoshiRemi en-aut-sei=Sumiyoshi en-aut-mei=Remi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UjiieHideki en-aut-sei=Ujiie en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaharaYuri en-aut-sei=Kawahara en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KogaTomohiro en-aut-sei=Koga en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UekiMasao en-aut-sei=Ueki en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LaczkoDorottya en-aut-sei=Laczko en-aut-mei=Dorottya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 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=13 ORCID= en-aut-name=KawakamiAtsushi en-aut-sei=Kawakami en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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 General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=6 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=9 en-affil=School of Information and Data Sciences, Nagasaki University kn-affil= affil-num=10 en-affil=Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania kn-affil= affil-num=11 en-affil=Department of Clinical Immunology, H?pital Saint-Louis kn-affil= affil-num=12 en-affil=Center for Cytokine Storm Treatment and Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Myeloma Center, University of Arkansas for Medical Sciences kn-affil= affil-num=14 en-affil=The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease, TAFRO and Related Ddisease Research Group kn-affil= affil-num=15 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=clinical subtype kn-keyword=clinical subtype en-keyword=histopathological criteria kn-keyword=histopathological criteria en-keyword=idiopathic multicentric castleman disease kn-keyword=idiopathic multicentric castleman disease en-keyword=lymphoproliferative disease kn-keyword=lymphoproliferative disease en-keyword=machine-learning kn-keyword=machine-learning END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=7 article-no= start-page=1152 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240717 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Metatranscriptomic Sequencing of Sheath Blight-Associated Isolates of Rhizoctonia solani Revealed Multi-Infection by Diverse Groups of RNA Viruses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice sheath blight, caused by the soil-borne fungus Rhizoctonia solani (teleomorph: Thanatephorus cucumeris, Basidiomycota), is one of the most devastating phytopathogenic fungal diseases and causes yield loss. Here, we report on a very high prevalence (100%) of potential virus-associated double-stranded RNA (dsRNA) elements for a collection of 39 fungal strains of R. solani from the rice sheath blight samples from at least four major rice-growing areas in the Philippines and a reference isolate from the International Rice Research Institute, showing different colony phenotypes. Their dsRNA profiles suggested the presence of multiple viral infections among these Philippine R. solani populations. Using next-generation sequencing, the viral sequences of the three representative R. solani strains (Ilo-Rs-6, Tar-Rs-3, and Tar-Rs-5) from different rice-growing areas revealed the presence of at least 36 viruses or virus-like agents, with the Tar-Rs-3 strain harboring the largest number of viruses (at least 20 in total). These mycoviruses or their candidates are believed to have single-stranded RNA or dsRNA genomes and they belong to or are associated with the orders Martellivirales, Hepelivirales, Durnavirales, Cryppavirales, Ourlivirales, and Ghabrivirales based on their coding-complete RNA-dependent RNA polymerase sequences. The complete genome sequences of two novel RNA viruses belonging to the proposed family Phlegiviridae and family Mitoviridae were determined. en-copyright= kn-copyright= en-aut-name=UrzoMichael Louie R. en-aut-sei=Urzo en-aut-mei=Michael Louie R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GuintoTimothy D. en-aut-sei=Guinto en-aut-mei=Timothy D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Eusebio-CopeAna en-aut-sei=Eusebio-Cope en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BudotBernard O. en-aut-sei=Budot en-aut-mei=Bernard O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanoriaMary Jeanie T. en-aut-sei=Yanoria en-aut-mei=Mary Jeanie T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JonsonGilda B. en-aut-sei=Jonson en-aut-mei=Gilda B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ArakawaMasao en-aut-sei=Arakawa en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= affil-num=1 en-affil=Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Ba?os kn-affil= affil-num=2 en-affil=Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Ba?os kn-affil= affil-num=3 en-affil=Fit-for-Future Genetic Resources Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=4 en-affil=Institute of Weed Science, Entomology, and Plant Pathology, College of Agriculture and Food Science, University of the Philippines Los Ba?os kn-affil= affil-num=5 en-affil=Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=6 en-affil=Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=7 en-affil=Faculty of Agriculture, Meijo University kn-affil= affil-num=8 en-affil=Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=9 en-affil=Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Rhizoctonia solani kn-keyword=Rhizoctonia solani en-keyword=dsRNA kn-keyword=dsRNA en-keyword=mycovirus kn-keyword=mycovirus en-keyword=RNA virus kn-keyword=RNA virus en-keyword=metatranscriptome kn-keyword=metatranscriptome END start-ver=1.4 cd-journal=joma no-vol=166 cd-vols= no-issue=8 article-no= start-page=bqaf102 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuromedin U Deficiency Disrupts Daily Testosterone Fluctuation and Reduces Wheel-running Activity in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=The objective of this study was to elucidate the role of endogenous Neuromedin U (NMU) in rats by performing NMU knockout (KO). Male, but not female NMU KO rats exhibited decreased wheel-running activity vs wildtype (WT), although overall home cage activity was not affected. Plasma testosterone in WT rats varied significantly over the course of a day, with a peak at ZT1 and a nadir at ZT18, whereas in NMU KO rats testosterone remained stable throughout the day. Chronic administration of testosterone restored wheel-running activity in NMU KO rats to the same level as in WT rats, suggesting that the decrease in wheel-running activity in NMU KO rats is due to the disruption of the diurnal change of testosterone. Accordingly, expression of the luteinizing hormone beta subunit (Lhb) mRNA in the pars distalis of anterior pituitary was significantly lower in NMU KO rats; immunostaining revealed that the size of luteinizing hormone (LH)?expressing cells was also relatively small in those animals. In the brain of male WT rats, Nmu was highly expressed in the pars tuberalis, and the NMU receptor Nmur2 was highly expressed in the ependymal cell layer of the third ventricle. This study reveals a novel function of NMU and indicates that endogenous NMU in rats plays a role in the regulation of motivated activity via regulation of testosterone. en-copyright= kn-copyright= en-aut-name=OtsukaMai en-aut-sei=Otsuka en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeuchiYu en-aut-sei=Takeuchi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriyamaMaho en-aut-sei=Moriyama en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EgoshiSakura en-aut-sei=Egoshi en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoYuki en-aut-sei=Goto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GuTingting en-aut-sei=Gu en-aut-mei=Tingting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimuraAtsushi P en-aut-sei=Kimura en-aut-mei=Atsushi P kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaraguchiShogo en-aut-sei=Haraguchi en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=MatsuyamaMakoto en-aut-sei=Matsuyama en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=BentleyGeorge E en-aut-sei=Bentley en-aut-mei=George E kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Biology, Faculty of Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Department of Biological Sciences, Faculty of Science, Hokkaido University kn-affil= affil-num=8 en-affil=Department of Biochemistry, Showa University School of Medicine kn-affil= affil-num=9 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=12 en-affil=Department of Integrative Biology and Helen Wills Neuroscience Institute, University of California at Berkeley kn-affil= affil-num=13 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Neuromedin U kn-keyword=Neuromedin U en-keyword=rat kn-keyword=rat en-keyword=motivation kn-keyword=motivation en-keyword=activity kn-keyword=activity en-keyword=testosterone kn-keyword=testosterone en-keyword=wheel-running kn-keyword=wheel-running END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=2 article-no= start-page=232 end-page=243 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=Outcomes of allogeneic SCT versus tisagenlecleucel in patients with R/R LBCL and poor prognostic factors en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the efficacy of tisagenlecleucel (tisa-cel) and allogeneic hematopoietic stem cell transplantation (allo-SCT) for patients with relapsed and/or refractory (r/r) large B-cell lymphoma (LBCL) with poor prognostic factors, defined as performance status (PS)???2, multiple extranodal lesions (EN), chemorefractory disease, or higher lactate dehydrogenase (LDH). Overall, the allo-SCT group demonstrated worse progression-free survival (PFS), higher non-relapse mortality, and a similar relapse/progression rate. Notably, the tisa-cel group showed better PFS than the allo-SCT group among patients with chemorefractory disease (3.2 vs. 2.0 months, p?=?0.092) or higher LDH (4.0 vs. 2.0 months, p =?0.018), whereas PFS in the two cellular therapy groups was similar among those with PS???2 or multiple EN. Survival time after relapse post-cellular therapy in patients with poor prognostic factors was 1.6 with allo-SCT and 4.6 months with tisa-cel. These findings were confirmed in a propensity score matching cohort. In conclusion, tisa-cel resulted in better survival than allo-SCT in patients with poor prognostic factors. However, patients who relapsed post-cellular therapy had dismal outcomes regardless of therapy. Further strategies are warranted to improve outcomes in these patients. en-copyright= kn-copyright= en-aut-name=HayashinoKenta en-aut-sei=Hayashino en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=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=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= en-keyword=Large B-cell lymphoma kn-keyword=Large B-cell lymphoma en-keyword=Allogeneic hematopoietic stem cell transplantation kn-keyword=Allogeneic hematopoietic stem cell transplantation en-keyword=CAR-T cell therapy kn-keyword=CAR-T cell therapy en-keyword=Tisagenlecleucel kn-keyword=Tisagenlecleucel en-keyword=Poor prognostic factors kn-keyword=Poor prognostic factors END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=5 article-no= start-page=759 end-page=762 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250301 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel De Novo Variant in KCNH5 in a Patient with Refractory Epileptic Encephalopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=We herein report a novel de novo KCNH5 variant in a patient with refractory epileptic encephalopathy. The patient exhibited seizures at 1 year and 7 months old, which gradually worsened, leading to a bedridden status. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and cerebellar hypoplasia. A trio whole-exome sequence analysis identified a de novo heterozygous c.640A>C, p.Lys214Gln variant in KCNH5 that was predicted to be deleterious. Recent studies have linked KCNH5 to various epileptic encephalopathies, with many patients showing normal MRI findings. The present case expands the clinical spectrum of the disease, as it is characterized by severe neurological prognosis, cerebral atrophy, and cerebellar hypoplasia. en-copyright= kn-copyright= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NaitoTatsuhiko en-aut-sei=Naito en-aut-mei=Tatsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaradaHiroaki en-aut-sei=Harada en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujioKeishi en-aut-sei=Fujio en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujishiroJun en-aut-sei=Fujishiro en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriHarushi en-aut-sei=Mori en-aut-mei=Harushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorishitaShinichi en-aut-sei=Morishita en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Rheumatology and Allergy, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Rheumatology and Allergy, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Radiology, School of Medicine, Jichi Medical University kn-affil= affil-num=10 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=epileptic encephalopathy kn-keyword=epileptic encephalopathy en-keyword=whole-exome sequencing kn-keyword=whole-exome sequencing en-keyword=KCNH5 kn-keyword=KCNH5 en-keyword=de novo variant kn-keyword=de novo variant 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=20250303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recent progress in oculopharyngodistal myopathy research from clinical and genetic viewpoints en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oculopharyngodistal myopathy (OPDM) is a rare muscular disorder characterized by ocular symptoms, pharyngeal symptoms, facial weakness, and distal predominant limb muscle weakness. The cause of the disease was unknown for a long time. Recently, however, it has been reported that expansions of CGG or CCG repeats in LRP12, LOC642361/NUTM2B-AS1, GIPC1, NOTCH2NLC, RILPL1, and ABCD3 are the causes of the disease. Cases sometimes present with neurological symptoms, and the clinical spectrum of diseases caused by expansions of CGG or CCG repeats has been proposed to be called FNOP-spectrum disorder after the names of fragile X-associated tremor/ataxia syndrome, neuronal intranuclear inclusion disease, oculopharyngeal myopathy with leukoencephalopathy, and OPDM. In this article, the recent progress in the field of OPDM is reviewed, and remaining issues in OPDM are discussed. en-copyright= kn-copyright= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=oculopharyngodistal myopathy kn-keyword=oculopharyngodistal myopathy en-keyword=CGG repeat kn-keyword=CGG repeat en-keyword=CCG repeat kn-keyword=CCG repeat en-keyword=repeat motif?phenotype correlation kn-keyword=repeat motif?phenotype correlation en-keyword=FNOP-spectrum disorder kn-keyword=FNOP-spectrum disorder END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=6 article-no= start-page=388.e1 end-page=388.e14 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=Clinical effects of granulocyte colony-stimulating factor administration and the timing of its initiation on allogeneic hematopoietic cell transplantation outcomes for myelodysplastic syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Granulocyte colony-stimulating factor (G-CSF) accelerates neutrophil recovery after allogeneic hematopoietic cell transplantation (HCT). However, the optimal use of G-CSF and the timing of its initiation after allogeneic HCT for myelodysplastic syndrome (MDS) according to graft type have not been determined. This retrospective study aimed to investigate the effects of using G-CSF administration and the timing of its initiation on transplant outcomes in adult patients with MDS undergoing allogeneic HCT. Using Japanese registry data, we retrospectively investigated the effects of G-CSF administration and the timing of its initiation on transplant outcomes among 4140 adults with MDS after bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), or single-unit cord blood transplantation (CBT) between 2013 and 2022. Multivariate analysis showed that early (days 0 to 4) and late (days 5 to 10) G-CSF administration significantly accelerated neutrophil recovery compared with no G-CSF administration following BMT, PBSCT, and CBT, but there was no benefit of early G-CSF initiation for early neutrophilic recovery regardless of graft type. Late G-CSF initiation was significantly associated with a higher risk of overall chronic GVHD following PBSCT (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.18 to 2.24; P = .002) and CBT (HR, 2.09; 95% CI, 1.21 to 3.60; P = .007) compared with no G-CSF administration. Late G-CSF initiation significantly improved OS compared with no G-CSF administration only following PBSCT (HR, 0.74; 95% CI, 0.58 to 0.94; P = .015). However, G-CSF administration and the timing of its initiation did not affect acute GVHD, relapse, or non-relapse mortality, irrespective of graft type. These results suggest that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT, but increased risk of overall chronic GVHD after PBSCT and CBT. However, the effect of early and late G-CSF initiation on transplant outcomes needs further study in adult patients with MDS. en-copyright= kn-copyright= en-aut-name=KonumaTakaaki en-aut-sei=Konuma en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiokaMachiko en-aut-sei=Fujioka en-aut-mei=Machiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FuseKyoko en-aut-sei=Fuse en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosoiHiroki en-aut-sei=Hosoi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasamotoYosuke en-aut-sei=Masamoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchidaNaoyuki en-aut-sei=Uchida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SawaMasashi en-aut-sei=Sawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishidaTetsuya en-aut-sei=Nishida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshikawaJun en-aut-sei=Ishikawa en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakamaeHirohisa en-aut-sei=Nakamae en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HasegawaYuta en-aut-sei=Hasegawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OnizukaMakoto en-aut-sei=Onizuka en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MaedaTakeshi en-aut-sei=Maeda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawamuraKoji en-aut-sei=Kawamura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhbikiMarie en-aut-sei=Ohbiki en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ItonagaHidehiro en-aut-sei=Itonaga en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Hematology, Sasebo City General Hospital kn-affil= affil-num=3 en-affil=Faculty of Medicine, Department of Hematology, Endocrinology and Metabolism, Niigata University kn-affil= affil-num=4 en-affil=Department of Hematology/Oncology, Wakayama Medical University kn-affil= affil-num=5 en-affil=Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital kn-affil= affil-num=6 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=7 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Kanagawa Cancer Center kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Anjo Kosei Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital kn-affil= affil-num=11 en-affil=Department of Hematology, Osaka International Cancer Institute 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, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Tokai University School of Medicine kn-affil= affil-num=16 en-affil=Department of Hematology and oncology, Kurashiki Central Hospital kn-affil= affil-num=17 en-affil=Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Department of Hematology, Tottori University Hospital kn-affil= affil-num=19 en-affil=Division of Hematology, Jichi Medical University kn-affil= affil-num=20 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=21 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=22 en-affil=Transfusion and Cell Therapy Unit, Nagasaki University Hospital kn-affil= en-keyword=Granulocyte colony-stimulating factor kn-keyword=Granulocyte colony-stimulating factor en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Bone marrow transplantation kn-keyword=Bone marrow transplantation en-keyword=Peripheral blood stem cell transplantation kn-keyword=Peripheral blood stem cell transplantation en-keyword=Cord blood transplantation kn-keyword=Cord blood transplantation en-keyword=Myelodysplastic syndrome kn-keyword=Myelodysplastic syndrome END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=2 article-no= start-page=145 end-page=148 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The trochlea for the intermediate tendon of the digastric muscle: a review en-subtitle= kn-subtitle= en-abstract= kn-abstract=This review explores the novel perspective that the intermediate tendon of the digastric muscle may function as an anatomical trochlear pulley system within the human body, challenging the traditional understanding of trochlear systems. While widely recognized trochlear units include structures like the medial part of the humerus and the superior oblique muscle of the orbit, the review focuses on the unique anatomical arrangement of the intermediate tendon of the digastric muscle in connection with the anterior and posterior bellies of the digastric muscles. Despite current debates within the anatomical community about labeling the digastric muscles as having a trochlea, this paper delves into the scientific definition of a trochlear pulley system, presenting the intermediate tendon of the digastric muscle as a potential trochlea. en-copyright= kn-copyright= en-aut-name=du PlooyXander en-aut-sei=du Plooy en-aut-mei=Xander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CardonaJuan J. en-aut-sei=Cardona en-aut-mei=Juan J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TabiraYoko en-aut-sei=Tabira en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BubbKathleen Carol en-aut-sei=Bubb en-aut-mei=Kathleen Carol kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RaeburnKazzara en-aut-sei=Raeburn en-aut-mei=Kazzara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TubbsR. Shane en-aut-sei=Tubbs en-aut-mei=R. Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Tulane University School of Medicine kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine kn-affil= affil-num=4 en-affil=Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine kn-affil= affil-num=5 en-affil=Anatomy Division, Department of Radiology, Weill Cornell Medical College kn-affil= affil-num=6 en-affil=Department of Anatomical Sciences, St. Georgefs University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine kn-affil= affil-num=9 en-affil=Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine kn-affil= en-keyword=Digastric muscles kn-keyword=Digastric muscles en-keyword=Intermediate tendon kn-keyword=Intermediate tendon en-keyword=Trochlea kn-keyword=Trochlea en-keyword=Anatomy kn-keyword=Anatomy en-keyword=Fascia kn-keyword=Fascia END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=23 article-no= start-page=235104 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Imaging valley-vortex edge modes in a phononic crystal at ultrahigh frequencies en-subtitle= kn-subtitle= en-abstract= kn-abstract=We perform optical measurements and numerical simulations of guided phonon propagation in novel topological phononic crystal structures at ultrahigh frequencies. The structures support valley-polarized states that exhibit an energy vortex nature and propagate with high efficiency at domain boundaries because backscattering is suppressed due to conservation of time reversal symmetry. We extract frequency- and time-resolved spatial mode patterns and k-space images, together with dispersion relations. We investigate the conditions required for robust propagation along interfaces and thereby observe very high efficiency waveguiding. en-copyright= kn-copyright= en-aut-name=OtsukaP. H. en-aut-sei=Otsuka en-aut-mei=P. H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TomodaM. en-aut-sei=Tomoda en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HatanakaD. en-aut-sei=Hatanaka en-aut-mei=D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamaguchiH. en-aut-sei=Yamaguchi en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsurutaK. en-aut-sei=Tsuruta en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsudaO. en-aut-sei=Matsuda en-aut-mei=O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Applied Physics, Graduate School of Engineering, Hokkaido University kn-affil= affil-num=2 en-affil=Division of Applied Physics, Graduate School of Engineering, Hokkaido University kn-affil= affil-num=3 en-affil=NTT Basic Research Laboratories, NTT Corporation kn-affil= affil-num=4 en-affil=NTT Basic Research Laboratories, NTT Corporation kn-affil= affil-num=5 en-affil=Department of Electrical and Electronic Engineering, Okayama University kn-affil= affil-num=6 en-affil=Division of Applied Physics, Graduate School of Engineering, Hokkaido University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sulfur dioxide-induced guard cell death and stomatal closure are attenuated in nitrate/proton antiporter AtCLCa mutants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Guard cells surrounding the stomata play a crucial role in regulating the entrance of hazardous gases such as SO2 into leaves. Stomatal closure could be a plant response to mitigate SO2 damage, although the mechanism for SO2-induced closure remains controversial. Proposed mediators for SO2-induced stomatal closure include phytohormones, reactive oxygen species, gasotransmitters, and cytosolic acidification. In this study, we investigated the mechanism of stomatal closure in Arabidopsis in response to SO2. Despite an increment in auxin and jasmonates after SO2 exposure, the addition of auxin did not cause stomatal closure and jasmonate-insensitive mutants exhibited SO2-induced stomatal closure suggesting auxin and jasmonates are not mediators leading to the closure. In addition, supplementation of scavenging reagents for reactive oxygen species and gasotransmitters did not inhibit SO2-induced closure. Instead, we found that cytosolic acidification is a credible mechanism for SO2-induced stomatal closure in Arabidopsis. CLCa mutants coding H+/nitrate antiporter, involved in cytosolic pH homeostasis, showed less sensitive stomatal phenotype against SO2. These results suggest that cytosolic pH homeostasis plays a tenable role in SO2 response in guard cells. en-copyright= kn-copyright= en-aut-name=OoiLia en-aut-sei=Ooi en-aut-mei=Lia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuuraTakakazu en-aut-sei=Matsuura en-aut-mei=Takakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=airborne pollutants kn-keyword=airborne pollutants en-keyword=cytosolic acidification kn-keyword=cytosolic acidification en-keyword=stomatal closure kn-keyword=stomatal closure en-keyword=sulfur dioxide kn-keyword=sulfur dioxide END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=32 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=Stability and water solubility of calcium ferrite-type aluminum-rich phase: implications for deep water cycle caused by subducting basaltic crusts en-subtitle= kn-subtitle= en-abstract= kn-abstract=The subducting crustal materials serve as a crucial channel for transporting water to the lower mantle. Recent experimental studies suggest that crustal materials such as basaltic crust can be a main water carrier and reservoir playing an important role on water cycling in the lower mantle. Despite being a primary mineral in crustal materials, the water solubility of calcium ferrite-type (CF) phase and its stability are unclear yet. A recent phase relation study of hydrous basalts showed Na-depletion in lower-mantle minerals, suggesting the presence of fluid possibly with high Na concentration and the absence of CF phase along the low-temperature slab geotherms, where Al-rich hydrous phase H and ferropericlase appear instead. These phases could consequently produce Na-depleted CF phase when reaching the dehydration temperature of Al-rich hydrous phase H. In this study, we investigated the stability and water solubility of CF-type MgAl2O4, which is a main CF component in a hydrous basalt, in water-bearing systems at 26?32 GPa and 1200?1900 ‹C using a Kawai-type multi-anvil press. Our results indicate that the stability of the CF phase is strongly influenced by water content in the system. Water contents of recovered CF phases estimated by Fourier-transform infrared spectroscopy show a limited variation between 73 and 87 ppm wt at a pressure of 26 GPa and temperatures of 1500?1900 ‹C. We suggest that CF phase could not be a primary water carrier at lower mantle depths. This emphasizes contributions of hydrous aluminous silica minerals to Earthfs deep water cycling and heterogeneous structures in the lower mantle due to the strong water partitioning to this phase compared with other constituent minerals. en-copyright= kn-copyright= en-aut-name=ZhangXinyue en-aut-sei=Zhang en-aut-mei=Xinyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MashinoIzumi en-aut-sei=Mashino en-aut-mei=Izumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Deep Space Exploration Laboratory/School of Earth and Space Sciences, University of Science and Technology of China kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Institute for Planetary Materials, Okayama University kn-affil= en-keyword=Water solubility kn-keyword=Water solubility en-keyword=CF phase kn-keyword=CF phase en-keyword=Single crystal kn-keyword=Single crystal en-keyword=FTIR kn-keyword=FTIR en-keyword=MORB kn-keyword=MORB END