start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=2 article-no= start-page=141 end-page=145 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Necrotizing Fasciitis Caused by ESBL-Producing Raoultella ornithinolytica in an Immunocompromised Patient with VEXAS Syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory somatic) syndrome has a poor prognosis, with infections being a major cause of death. Raoultella ornithinolytica is an environmental bacterium found predominantly in soil and water. Although R. ornithinolytica can cause various infections, necrotizing fasciitis due to this bacterium has not been reported. We describe the case of an 84-year-old Japanese male with VEXAS syndrome who developed septic shock and necrotizing fasciitis while he was under immunosuppressive therapy. The pathogen was initially misidentified as R. planticola by mass spectrometry but later confirmed by whole-genome sequencing as extended spectrum β-lactamase (ESBL) produced by R. ornithinolytica. Although a life-saving leg amputation was required, the patient recovered with appropriate antibiotic therapy. R. ornithinolytica is thus able to cause severe skin infections in immunocompromised individuals. en-copyright= kn-copyright= en-aut-name=Sakamoto-TokunagaMoe en-aut-sei=Sakamoto-Tokunaga en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MatobaMasaki en-aut-sei=Matoba en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TamuraTomokazu en-aut-sei=Tamura en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KubotaNatsuki en-aut-sei=Kubota en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=ShidaharaKenta en-aut-sei=Shidahara en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiroseKei en-aut-sei=Hirose en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumotoKazuya en-aut-sei=Matsumoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NawachiShoichi en-aut-sei=Nawachi en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakadoiTakato en-aut-sei=Nakadoi en-aut-mei=Takato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KatayamaYu en-aut-sei=Katayama en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HayashiKeigo en-aut-sei=Hayashi en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Takano-NarazakiMariko en-aut-sei=Takano-Narazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= en-aut-name=SadaKen-Ei en-aut-sei=Sada en-aut-mei=Ken-Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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=22 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=23 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=24 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=21 en-affil=Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=22 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=23 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=24 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=necrotizing fasciitis kn-keyword=necrotizing fasciitis en-keyword=Raoultella ornithinolytica kn-keyword=Raoultella ornithinolytica en-keyword=VEXAS syndrome kn-keyword=VEXAS syndrome en-keyword=whole-genome sequence kn-keyword=whole-genome sequence END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=2 article-no= start-page=131 end-page=139 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Proteinuria on Postoperative Complications Following Colorectal Cancer Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colorectal surgery is associated with a high incidence of postoperative complications regardless of the advances in surgical techniques and multidisciplinary treatment. Proteinuria is common in patients with malignancies, but few studies have investigated the association between preoperative proteinuria and patient prognoses, especially postoperative complications. We investigated the impact of proteinuria on patients undergoing colorectal surgery in a single-center, retrospective cohort study of 767 patients who underwent surgical resection for colorectal cancer between January 2016 and December 2022 at the National Hospital Organization Shikoku Cancer Center. Among them, 81 patients with preoperative proteinuria were compared with the control group of 686 patients without proteinuria. Our analyses revealed that the patients with proteinuria had malnutrition with a significantly lower prognostic nutritional index compared to the no-proteinuria control group (p<0.001). The proteinuria group had a significantly advanced tumor stage (p=0.005), experienced more bleeding during the surgery (p=0.002), and required more transfusions (p<0.001). Postoperative complications were significantly more frequent in the proteinuria group (p=0.03), thus demonstrating that proteinuria was independently associated with postoperative complications (p=0.045). Proteinuria in patients undergoing colorectal cancer surgery can therefore be considered a risk factor for postoperative complications. en-copyright= kn-copyright= en-aut-name=NakataShunsuke en-aut-sei=Nakata en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakatsuFumiaki en-aut-sei=Takatsu en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MikuriyaYoshihiro en-aut-sei=Mikuriya en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakishitaTomokazu en-aut-sei=Kakishita en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HatoShinji en-aut-sei=Hato en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtaKoji en-aut-sei=Ohta en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobatakeTakaya en-aut-sei=Kobatake en-aut-mei=Takaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=surgery kn-keyword=surgery en-keyword=proteinuria kn-keyword=proteinuria en-keyword=complication kn-keyword=complication en-keyword=malnutrition kn-keyword=malnutrition END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue= article-no= start-page=103134 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Regulation of brain-specific kinases 1 and 2 (BRSK1/2) by Ca2+/calmodulin en-subtitle= kn-subtitle= en-abstract= kn-abstract=We conducted a genome-wide calmodulin (CaM) interaction screening of 462 GST-fused human protein kinases to identify novel CaM-dependent protein kinases (CaMKs). In addition to known CaMKs, including myosin light chain kinases, CaMK2γ, and death-associated kinase 2, we identified the brain-specific protein kinase 2 (BRSK2, also known as SAD-A) as a novel CaM interactant. Proximity biotinylation and CaM–sepharose chromatography assays revealed that rat BRSK isoforms (BRSK1/2) interact with CaM in a Ca2+-dependent manner in vitro. We found that CaM suppresses the activation-loop phosphorylation of BRSK1 (at Thr189) and BRSK2 (at Thr175) by liver kinase B1 (LKB1), an activating kinase, in a Ca2+-dependent manner (IC50 of ∼7 µM), thereby inhibiting BRSK activation. LKB1-catalyzed phosphorylation of the catalytic domain mutant of BRSK1 (residues 1–294) at Thr189 was suppressed by the addition of Ca2+/CaM, consistent with direct CaM binding of the kinase domain, as well as wild-type BRSK1. We confirmed that the LKB1 activity was not directly suppressed by Ca2+/CaM, supporting the hypothesis that the direct interaction of Ca2+/CaM with the kinase domain blocks the phosphorylation/activation of BRSK1/2 by LKB1. The kinase activity and PP2Cα-catalyzed dephosphorylation of LKB1-phosphorylated BRSK1 were not altered by Ca2+/CaM, although it was demonstrated to bind to Ca2+/CaM like that of unphosphorylated BRSK1. This unrecognized mechanism of BRSK1/2 regulation, involving the direct role of Ca2+/CaM binding, which inhibits phosphorylation/activation by LKB1, may open a new Ca2+ signal transduction pathway in neurons. en-copyright= kn-copyright= en-aut-name=WashidaNaoyuki en-aut-sei=Washida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KataokaMoe en-aut-sei=Kataoka en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BrunAnna R. en-aut-sei=Brun en-aut-mei=Anna R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakezakiUryu en-aut-sei=Takezaki en-aut-mei=Uryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HijikawaKo en-aut-sei=Hijikawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamauchiHaruki en-aut-sei=Yamauchi en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=MorishitaRyo en-aut-sei=Morishita en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil= 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 Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=6 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=CellFree Sciences Co., Ltd. kn-affil= affil-num=10 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=BRSK1 kn-keyword=BRSK1 en-keyword=BRSK2 kn-keyword=BRSK2 en-keyword=calmodulin kn-keyword=calmodulin en-keyword=LKB1 kn-keyword=LKB1 en-keyword=phosphorylation kn-keyword=phosphorylation en-keyword=Ca2+ kn-keyword=Ca2+ en-keyword=CaM-dependent protein kinase kn-keyword=CaM-dependent protein kinase END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue= article-no= start-page=49 end-page=57 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Advanced Hospital Training Activities in Fiscal 2025 kn-title=2025 年度における「先進病院実習」の取り組み en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MORITAMizuki en-aut-sei=MORITA en-aut-mei=Mizuki kn-aut-name=森田瑞樹 kn-aut-sei=森田 kn-aut-mei=瑞樹 aut-affil-num=1 ORCID= en-aut-name=MAGARIMasaki en-aut-sei=MAGARI en-aut-mei=Masaki kn-aut-name=曲正樹 kn-aut-sei=曲 kn-aut-mei=正樹 aut-affil-num=2 ORCID= en-aut-name=WangJin en-aut-sei=Wang en-aut-mei=Jin kn-aut-name=王璡 kn-aut-sei=王 kn-aut-mei=璡 aut-affil-num=3 ORCID= en-aut-name=WATANABEToyohiko en-aut-sei=WATANABE en-aut-mei=Toyohiko kn-aut-name=渡邉豊彦 kn-aut-sei=渡邉 kn-aut-mei=豊彦 aut-affil-num=4 ORCID= en-aut-name=OITAMasataka en-aut-sei=OITA en-aut-mei=Masataka kn-aut-name=笈田将皇 kn-aut-sei=笈田 kn-aut-mei=将皇 aut-affil-num=5 ORCID= en-aut-name=HARADANahoko en-aut-sei=HARADA en-aut-mei=Nahoko kn-aut-name=原田奈穂子 kn-aut-sei=原田 kn-aut-mei=奈穂子 aut-affil-num=6 ORCID= en-aut-name=SHISHIDOKeisuke en-aut-sei=SHISHIDO en-aut-mei=Keisuke kn-aut-name=宍戸圭介 kn-aut-sei=宍戸 kn-aut-mei=圭介 aut-affil-num=7 ORCID= affil-num=1 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=2 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=3 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=4 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=5 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=6 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=7 en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=dmm052605 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Congenital intestinal atresia (IA) is a birth defect characterised by the absence or closure of part of the intestine. Although genetic factors are implicated, mechanistic understanding has been hindered by the lack of suitable animal models. Here, we describe a medaka (Oryzias latipes) mutant, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, that develops IA during embryogenesis. Positional cloning identified a nonsense mutation in mypt1, encoding myosin phosphatase target subunit 1. Mutant embryos exhibited ectopic accumulation of F-actin and phosphorylated myosin regulatory light chain (Mrlc) in the intestinal epithelium, consistent with disrupted actomyosin regulation. These cytoskeletal abnormalities were accompanied by epithelial disorganisation, without notable alterations in cell proliferation, motility or apoptosis. Inhibition of myh11a, encoding smooth muscle (SM) myosin heavy chain, ameliorated the IA phenotype, whereas blebbistatin treatment completely rescued the defect, suggesting a non-contractile role prior to SM maturation. Together, these findings demonstrate that mypt1 loss disrupts intestinal morphogenesis through actomyosin dysregulation. Given the recent clinical identification of IA associated with MYPT1 variants, this medaka model offers a valuable platform to investigate the developmental and molecular basis of MYPT1-associated IA in humans. en-copyright= kn-copyright= en-aut-name=KobayashiDaisuke en-aut-sei=Kobayashi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UrasakiAkihiro en-aut-sei=Urasaki en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraTetsuaki en-aut-sei=Kimura en-aut-mei=Tetsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuoKazuhiko en-aut-sei=Matsuo en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YokoiHayato en-aut-sei=Yokoi en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakashimaShigeo en-aut-sei=Takashima en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitagawaTadao en-aut-sei=Kitagawa en-aut-mei=Tadao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KageTakahiro en-aut-sei=Kage en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaritaTakanori en-aut-sei=Narita en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=JindoTomoko en-aut-sei=Jindo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KinoshitaMasato en-aut-sei=Kinoshita en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NaruseKiyoshi en-aut-sei=Naruse en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakajimaYoshiro en-aut-sei=Nakajima en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShigetaMasaki en-aut-sei=Shigeta en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SakakiShinichiro en-aut-sei=Sakaki en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueSatoshi en-aut-sei=Inoue en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SabaRie en-aut-sei=Saba en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamadaKei en-aut-sei=Yamada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YokoyamaTakahiko en-aut-sei=Yokoyama en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IshikawaYuji en-aut-sei=Ishikawa en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ArakiKazuo en-aut-sei=Araki en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SagaYumiko en-aut-sei=Saga en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TakedaHiroyuki en-aut-sei=Takeda en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YashiroKenta en-aut-sei=Yashiro en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=2 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=3 en-affil=Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology kn-affil= affil-num=4 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=5 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=6 en-affil=Graduate School of Agricultural Science, Tohoku University kn-affil= affil-num=7 en-affil=Institute for Glyco-core Research (iGCORE)/Life Science Research Centre, Gifu University kn-affil= affil-num=8 en-affil=Program in Environmental Management, Graduate School of Agriculture, Kindai University kn-affil= affil-num=9 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=10 en-affil=Laboratory of Molecular Biology, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University kn-affil= affil-num=11 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=12 en-affil=Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=13 en-affil=Laboratory of Bioresources, National Institute for Basic Biology kn-affil= affil-num=14 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=15 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=16 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=17 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=18 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=19 en-affil=Department of Radiology, Kyoto Prefectural University of Medicine kn-affil= affil-num=20 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= affil-num=21 en-affil=Research Centre for Radiation Protection, National Institute of Radiological Sciences kn-affil= affil-num=22 en-affil=Research Center for Aquatic Breeding, National Research Institute of Aquaculture, Fisheries Research Agency kn-affil= affil-num=23 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=24 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=25 en-affil=Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine kn-affil= en-keyword=Intestinal atresia kn-keyword=Intestinal atresia en-keyword=Mypt1 kn-keyword=Mypt1 en-keyword=Disease model kn-keyword=Disease model en-keyword=Actomyosin regulation kn-keyword=Actomyosin regulation en-keyword=Intestinal development kn-keyword=Intestinal development END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=3 article-no= start-page=e198959 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collagen-binding C-type natriuretic peptide enhances chondrogenesis and osteogenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=C-type natriuretic peptide (CNP) is known to promote chondrocyte proliferation and bone formation; however, CNP’s extremely short half-life necessitates continuous intravascular administration to achieve bone-lengthening effects. Vosoritide, a CNP analog designed for resistance to neutral endopeptidase, allows for once-daily administration. Nonetheless, it distributes systemically rather than localizing to target tissues, which may result in adverse effects such as hypotension. To enhance local drug delivery and therapeutic efficacy, we developed a potentially novel synthetic protein by fusing a collagen-binding domain (CBD) to CNP, termed CBD-CNP. This fusion protein exhibited stability under heat conditions and retained the collagen-binding ability and bioactivity as CNP. CBD-CNP localized to articular cartilage in fetal murine tibiae and promoted bone elongation. Spatial transcriptomic analysis revealed that the upregulation of chondromodulin expression may contribute to its therapeutic effects. Treatment of CBD-CNP mixed with collagen powder to a fracture site of a mouse model increased bone mineral content and bone volume compared with CNP-22. Intraarticular injection of CBD-CNP to a mouse model of knee osteoarthritis suppressed subchondral bone thickening. By addressing the limitations of CNP’s rapid degeneration, CBD-CNP leverages its collagen-binding capacity to achieve targeted, sustained delivery in collagen-rich tissues, offering a promising strategy for enhancing chondrogenesis and osteogenesis. en-copyright= kn-copyright= en-aut-name=HiraiKenta en-aut-sei=Hirai en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawamuraKenta en-aut-sei=Sawamura en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EsakiRyusaku en-aut-sei=Esaki en-aut-mei=Ryusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SawadaRyusuke en-aut-sei=Sawada en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkushaYuka en-aut-sei=Okusha en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AoyamaEriko en-aut-sei=Aoyama en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoHiroki en-aut-sei=Saito en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchidaKentaro en-aut-sei=Uchida en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MimaTakehiko en-aut-sei=Mima en-aut-mei=Takehiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=MatsushitaMasaki en-aut-sei=Matsushita en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsushitaOsamu en-aut-sei=Matsushita en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of 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 Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Kitasato University School of Medicine kn-affil= affil-num=9 en-affil=Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences kn-affil= affil-num=10 en-affil=Department of Biochemistry and Molecular DentistryBacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=120 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of clinical practices during the transitional and young adult phases between patients with oligoarticular/polyarticular juvenile idiopathic arthritis and those with rheumatoid arthritis in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition that frequently persists into adulthood, posing long-term challenges in disease control and quality of life. However, clinical management during the transitional and young adult phases remains insufficiently characterized, especially in comparison with adult-onset rheumatoid arthritis (RA). This study aimed to compare disease activity, medication use, and treatment practices between patients with oligoarticular/polyarticular JIA and those with RA, focusing on individuals aged 16–30 years.
Methods Data were derived from two nationwide multicenter databases in Japan—NinJa (National Database of Rheumatic Diseases in Japan) for RA and CoNinJa (a pediatric counterpart of NinJa) for JIA. A total of 176 JIA and 152 RA patients, all aged 16–30 years, were analyzed. Clinical parameters, disease activity indices, and medication profiles were compared using the Mann–Whitney U test and Fisher’s exact test.
Results Compared to RA patients, JIA patients demonstrated significantly lower disease activity (median SDAI 0.6 vs. 2.4) and higher remission rates, particularly Boolean remission (70% vs. 44%) (p < 0.001). MTX usage was less frequent in JIA (49% vs. 68%, p < 0.001), whereas biologic use was notably more common (69% vs. 38%, p < 0.001), with 31% involving off-label prescriptions. Among patients in CDAI remission, biologic monotherapy was observed more frequently in JIA (29% vs. 7%, p < 0.001). Discontinuation of MTX was most commonly attributed to disease improvement (58%) or gastrointestinal intolerance (nausea, 29%). Subcutaneous tocilizumab, though unapproved for JIA in Japan, had the lowest discontinuation rate (4%), suggesting favorable tolerability.
Conclusions Despite an overlap in age, patients with JIA and RA exhibit distinct disease characteristics and therapeutic patterns. These differences underscore the need to expand approved treatment options for JIA, promote equitable access to biologics, and strengthen transitional care frameworks. Further research is warranted to explore long-term outcomes, reproductive health considerations, and socioeconomic barriers that influence treatment continuity in young adults with childhood-onset arthritis. en-copyright= kn-copyright= en-aut-name=MoriSho en-aut-sei=Mori en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShabanaKosuke en-aut-sei=Shabana en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuiToshihiro en-aut-sei=Matsui en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NozawaTomo en-aut-sei=Nozawa en-aut-mei=Tomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TomiitaMinako en-aut-sei=Tomiita en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagishiYasuo en-aut-sei=Nakagishi en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamasakiYuichi en-aut-sei=Yamasaki en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 ORCID= en-aut-name=YasumuraJunko en-aut-sei=Yasumura en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WakiguchiHiroyuki en-aut-sei=Wakiguchi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=TakezakiShunichiro en-aut-sei=Takezaki en-aut-mei=Shunichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkuraYuka en-aut-sei=Okura en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YokoyamaTadafumi en-aut-sei=Yokoyama en-aut-mei=Tadafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShimizuMasaki en-aut-sei=Shimizu en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HirayamaMasahiro en-aut-sei=Hirayama en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TohmaShigeto en-aut-sei=Tohma en-aut-mei=Shigeto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 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=22 ORCID= affil-num=1 en-affil=Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Osaka Medical and Pharmaceutical University kn-affil= affil-num=3 en-affil=Department of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Graduate School of Medicine, Yokohama City University kn-affil= affil-num=5 en-affil=Department of Pediatrics, Osaka Medical and Pharmaceutical University kn-affil= affil-num=6 en-affil=Department of Allergy and Rheumatology, Chiba Children’s Hospital kn-affil= affil-num=7 en-affil=Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children’s Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, Kagoshima University Hospital kn-affil= affil-num=9 en-affil=Department of General Pediatrics, Miyagi Children’s Hospital kn-affil= affil-num=10 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Infection and Immunology, Allergy and Immunology Center, Aichi Children’s Health and Medical Center kn-affil= affil-num=12 en-affil=Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences kn-affil= affil-num=13 en-affil=Department of Pediatrics, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Pediatrics, Chiba University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Pediatrics, Faculty of Medicinea and Graduate School of Medicine, Hokkaido University kn-affil= affil-num=16 en-affil=Center for Pediatric Allergy and Rheumatology, KKR Sapporo Medical Center kn-affil= affil-num=17 en-affil=Department of Pediatrics, Kanazawa University kn-affil= affil-num=18 en-affil=Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= affil-num=19 en-affil=Department of Pediatrics, Mie University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Rheumatology, National Hospital Organization Tokyo National Hospital kn-affil= affil-num=21 en-affil=Department of Pediatrics, Osaka Medical and Pharmaceutical University kn-affil= affil-num=22 en-affil=Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine kn-affil= en-keyword=Juvenile idiopathic arthritis kn-keyword=Juvenile idiopathic arthritis en-keyword=Rheumatoid arthritis kn-keyword=Rheumatoid arthritis en-keyword=Disease activity kn-keyword=Disease activity en-keyword=Biologics kn-keyword=Biologics en-keyword=Methotrexate kn-keyword=Methotrexate END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=TeMPRA: advancing continuing professional development in pediatric rheumatology in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background In the context of the global shortage of pediatric rheumatologists, mid-career specialists who can play key roles in regional education, research, and clinical practice have become increasingly important. In Japan, the Team of Mid-career Pediatric Rheumatologists Alliance (TeMPRA) was founded in 2014 to support continuing professional development (CPD) and foster collaboration among mid-career pediatric rheumatologists. The aim of this study was to characterize the current status and future perspectives of the TeMPRA members.
Methods In 2024, a cross-sectional, web-based survey was conducted among all 37 active members of the TeMPRA across Japan. Data were collected on career trajectories, educational roles, research activities, clinical practices, and international engagement. Categorical variables were compared using appropriate statistical tests, with a significance level of 0.05.
Results Responses were obtained from 35 members (response rate: 95%). Most respondents (71%) were affiliated with university hospitals, and 60% had > 10 years of experience in pediatric rheumatology. Compared with those working in community hospitals, respondents affiliated with university hospitals were significantly more likely to be involved in research activities (50% vs. 0%, P = 0.0261) and global professional contributions (88% vs. 0%, P < 0.0001). Overall, 54% of respondents were engaged in teaching students or early-career pediatric rheumatologists, while 43% were involved in clinical or basic research, most commonly focusing on juvenile idiopathic arthritis and systemic lupus erythematosus. Collectively, respondents were responsible for the care of 1,677 children with pediatric rheumatic diseases. While all respondents reported willingness to contribute to pediatric rheumatology at the regional level, 94% and 71% reported willingness to contribute at the national and global levels, respectively.
Conclusions This nationwide survey highlights the substantial educational roles, research activities, and clinical practices of mid-career pediatric rheumatologists in Japan and suggests that the TeMPRA framework can serve as a valuable model for supporting CPD and workforce sustainability. Similar alliance-based approaches may be applicable in other countries facing comparable challenges in pediatric rheumatology. en-copyright= kn-copyright= en-aut-name=WakiguchiHiroyuki en-aut-sei=Wakiguchi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HashimotoKunio en-aut-sei=Hashimoto en-aut-mei=Kunio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=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=AkamineKeiji en-aut-sei=Akamine en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UejimaYoji en-aut-sei=Uejima en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=YamasakiYuichi en-aut-sei=Yamasaki en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasumuraJunko en-aut-sei=Yasumura en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkazakiFumiko en-aut-sei=Okazaki en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KizawaToshitaka en-aut-sei=Kizawa en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YasuokaRyuhei en-aut-sei=Yasuoka en-aut-mei=Ryuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshikawaTomoaki en-aut-sei=Ishikawa en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=FujitaYuji en-aut-sei=Fujita en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ItohNaohiro en-aut-sei=Itoh en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakasakiAsami en-aut-sei=Takasaki en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SakuraiNodoka en-aut-sei=Sakurai en-aut-mei=Nodoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SuzukiKazuo en-aut-sei=Suzuki en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TamaiTasuku en-aut-sei=Tamai en-aut-mei=Tasuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HiranoNaoki en-aut-sei=Hirano en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 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=23 ORCID= en-aut-name=ShimizuMasaki en-aut-sei=Shimizu en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine kn-affil= affil-num=2 en-affil=Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Yokohama City University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kitasato University kn-affil= affil-num=6 en-affil=Department of Nephrology and Rheumatology, Tokyo Metropolitan Children’s Medical Center kn-affil= affil-num=7 en-affil=Division of Infectious Diseases and Immunology, Saitama Children’s Medical Center kn-affil= affil-num=8 en-affil=Clinical Education Center for Physicians, Shiga University of Medical Science kn-affil= affil-num=9 en-affil=Department of Pediatrics, Kagoshima University Hospital kn-affil= affil-num=10 en-affil=Department of Pediatrics, Hiroshima Prefectural Hospital Organization Futabanosato Prefectural Hospital kn-affil= affil-num=11 en-affil=Department of Pediatrics, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Japan Community Health Care Organization Sapporo Hokushin Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Hamamatsu University School of Medicine kn-affil= affil-num=14 en-affil=Department of Pediatrics, Nara Medical University kn-affil= affil-num=15 en-affil=Department of Pediatrics, Chiba University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Pediatrics, Dokkyo Medical University kn-affil= affil-num=17 en-affil=Department of Pediatrics, Faculty of Medical Sciences, University of Fukui kn-affil= affil-num=18 en-affil=Department of Pediatrics, School of Medicine, University of Toyama kn-affil= affil-num=19 en-affil=Department of Pediatrics, NTT East Medical Center Sapporo kn-affil= affil-num=20 en-affil=Suzuki Kids Clinic kn-affil= affil-num=21 en-affil=Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine kn-affil= affil-num=22 en-affil=Department of Public Health and Epidemiology, Faculty of Medicine, Oita University kn-affil= affil-num=23 en-affil=Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety kn-affil= affil-num=24 en-affil=Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo kn-affil= en-keyword=Child kn-keyword=Child en-keyword=Education kn-keyword=Education en-keyword=Juvenile idiopathic arthritis kn-keyword=Juvenile idiopathic arthritis en-keyword=Practice kn-keyword=Practice en-keyword=Rheumatic diseases kn-keyword=Rheumatic diseases en-keyword=Systemic lupus erythematosus kn-keyword=Systemic lupus erythematosus en-keyword=Team of mid-career pediatric rheumatologists alliance kn-keyword=Team of mid-career pediatric rheumatologists alliance END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue= article-no= start-page=103078 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=Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): long-term results of a multicentre, single-arm, phase 2 trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma for which prognosis is typically poor without a timely diagnosis. To explore the safety and efficacy of standard chemotherapy combined with central nervous system (CNS)-directed therapy, we conducted a multicentre, single-arm, phase 2 trial in untreated IVLBCL patients without CNS involvement at diagnosis (PRIMEUR-IVL). In the primary analysis, the PRIMEUR-IVL study demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence (3%) of secondary CNS involvement (sCNSi).
Methods We present a prespecified final analysis of the PRIMEUR-IVL study including 5-year PFS, OS and cumulative incidence of sCNSi. Participants were enrolled between June 2011 and July 2016, and the data cutoff date for the final analysis was 16 November 2021. The trial was registered in the UMIN Clinical Trial Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165).
Findings With a median follow-up of 7.1 years (interquartile range 5.6–8.7), 5-year PFS in all 37 eligible patients was 68% (95% confidence interval [CI] 50%–80%) and OS was 78% (95% CI 61%–89%). No additional sCNSi was observed after the primary analysis. Severe adverse events after the primary analysis were grade 4 neutropenia (n = 1) and grade 4 myelodysplastic syndrome that did not require specific treatment (n = 1). Eight deaths occurred during the observation period after enrolment, due to primary disease (n = 6), sepsis (n = 1) and unknown sudden death (n = 1).
Interpretation Long-term follow-up data demonstrated durable response for PFS and OS, and low cumulative incidence of sCNSi, indicating the efficacy of standard chemotherapy combined with CNS-directed therapy for untreated IVLBCL patients.
Funding This study received financial support from the Japan Agency for Medical Research and Development, Center for Supporting Hematology-Oncology Studies, and National Cancer Center. en-copyright= kn-copyright= en-aut-name=ShimadaKazuyuki en-aut-sei=Shimada en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaguchiMotoko en-aut-sei=Yamaguchi en-aut-mei=Motoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuwatsukaYachiyo en-aut-sei=Kuwatsuka en-aut-mei=Yachiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsueKosei en-aut-sei=Matsue en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKeijiro en-aut-sei=Sato en-aut-mei=Keijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KusumotoShigeru en-aut-sei=Kusumoto en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaiHirokazu en-aut-sei=Nagai en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakizawaJun en-aut-sei=Takizawa en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FukuharaNoriko en-aut-sei=Fukuhara en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagafujiKoji en-aut-sei=Nagafuji en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MiyazakiKana en-aut-sei=Miyazaki en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhtsukaEiichi en-aut-sei=Ohtsuka en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkamotoAkinao en-aut-sei=Okamoto en-aut-mei=Akinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SugitaYasumasa en-aut-sei=Sugita en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=UchidaToshiki en-aut-sei=Uchida en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KayukawaSatoshi en-aut-sei=Kayukawa en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WakeAtsushi en-aut-sei=Wake en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= en-aut-name=KondoYukio en-aut-sei=Kondo en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MeguroAkiko en-aut-sei=Meguro en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KinYoshihiro en-aut-sei=Kin en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MinamiYosuke en-aut-sei=Minami en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HashimotoDaigo en-aut-sei=Hashimoto en-aut-mei=Daigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NishiyamaTakahiro en-aut-sei=Nishiyama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ShimadaSatoko en-aut-sei=Shimada en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MasakiYasufumi en-aut-sei=Masaki en-aut-mei=Yasufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=OkamotoMasataka en-aut-sei=Okamoto en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KiyoiHitoshi en-aut-sei=Kiyoi en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SuzukiRitsuro en-aut-sei=Suzuki en-aut-mei=Ritsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=NakamuraShigeo en-aut-sei=Nakamura en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=KinoshitaTomohiro en-aut-sei=Kinoshita en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Hematological Malignancies, Mie University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Advanced Medicine, Nagoya University Hospital kn-affil= affil-num=4 en-affil=Division of Hematology/Oncology, Internal Medicine, Kameda Medical Center kn-affil= affil-num=5 en-affil=Department of Hematology, Nagano Red Cross Hospital kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=8 en-affil=Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine kn-affil= affil-num=9 en-affil=Department of Hematology and Rheumatology, Tohoku University Hospital kn-affil= affil-num=10 en-affil=Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Mie University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Hematology, Oita Prefectural Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Fujita Health University School of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Oami Municipal Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital kn-affil= affil-num=16 en-affil=Department of Clinical Oncology, Nagoya Memorial Hospital kn-affil= affil-num=17 en-affil=Department of Hematology, Toranomon Hospital Kajigaya kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Internal Medicine, Toyama Prefectural Central Hospital kn-affil= affil-num=20 en-affil=Division of Hematology, Tochigi Cancer Center kn-affil= affil-num=21 en-affil=Department of Hematology, Daini Osaka Police Hospital kn-affil= affil-num=22 en-affil=Department of Hematology, National Cancer Center Hospital East kn-affil= affil-num=23 en-affil=Department of Hematology, Hokkaido University Faculty of Medicine, Graduate School of Medicine kn-affil= affil-num=24 en-affil=Division of Hematology, Ichinomiya Municipal Hospital kn-affil= affil-num=25 en-affil=Department of Pathology and Clinical Laboratories, Nagoya University Hospital kn-affil= affil-num=26 en-affil=Department of Hematology and Immunology, Kanazawa Medical University kn-affil= affil-num=27 en-affil=Department of Hematology, Fujita Health University School of Medicine kn-affil= affil-num=28 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=29 en-affil=Department of Hematology and Oncology, Nagoya University Graduate School of Medicine kn-affil= affil-num=30 en-affil=Department of HSCT Data Management and Biostatistics, Nagoya University School of Medicine kn-affil= affil-num=31 en-affil=Department of Pathology and Clinical Laboratories, Nagoya University Hospital kn-affil= affil-num=32 en-affil=Department of Hematology and Cell Therapy, Aichi Cancer Center kn-affil= en-keyword=Central nervous system-directed therapy kn-keyword=Central nervous system-directed therapy en-keyword=Intravascular large B-Cell lymphoma kn-keyword=Intravascular large B-Cell lymphoma en-keyword=R-CHOP kn-keyword=R-CHOP en-keyword=Secondary central nervous system involvement kn-keyword=Secondary central nervous system involvement END start-ver=1.4 cd-journal=joma no-vol=153 cd-vols= no-issue=3 article-no= start-page=191 end-page=199 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of Schizophrenia Spectrum Disorders on the Receipt of Invasive and Systemic Therapy for Colorectal Cancer: A Nationwide Multicenter Retrospective Cohort Study in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: This study examined treatment disparities for colorectal cancer among patients diagnosed with schizophrenia spectrum disorders (SSD), focusing on invasive treatments and stage-appropriate systemic therapy within a universal healthcare system.
Method: In this nationwide retrospective cohort study (2018–2021), we identified 248,966 colorectal cancer patients, including 2337 diagnosed with SSD, using linked cancer registry and insurance claims data in Japan. The presence of SSD was classified according to ICD-10 codes F20–29. We used multivariable logistic regression to compare the odds of receiving stage-appropriate adjuvant chemotherapy and systemic therapy, as well as the odds of receiving surgical or endoscopic treatments, between the two groups. The analysis adjusted for age, sex, clinical stage, and scores on the Charlson Comorbidity Index and Barthel Index.
Results: The clinical stage distribution at diagnosis for colorectal cancer differed significantly between patients with SSD and those without psychiatric disorders (p < 0.001). After adjusting for clinical stage and other covariates, patients with SSD demonstrated significantly lower odds of receiving surgical or endoscopic treatment (adjusted odds ratio [aOR], 0.83; 95% CI, 0.73–0.94). The disparities were more pronounced for systemic therapy; patients with SSD had substantially lower odds of receiving adjuvant chemotherapy for stage III disease (aOR, 0.33; 95% CI, 0.26–0.41) and systemic therapy for stage IV disease (aOR, 0.23; 95% CI, 0.17–0.31).
Conclusion: Patients with SSD encounter substantial disparities in accessing standard colorectal cancer care, particularly systemic therapies. These findings highlight the urgent need for interventions to ensure equitable cancer treatment for this vulnerable population. en-copyright= kn-copyright= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiiTaisuke en-aut-sei=Ishii en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeTomone en-aut-sei=Watanabe en-aut-mei=Tomone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimoriMaiko en-aut-sei=Fujimori en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakayaNaoki en-aut-sei=Nakaya en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawamuraToshihiko en-aut-sei=Kawamura en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtsukiKoji en-aut-sei=Otsuki en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=ShimazuTaichi en-aut-sei=Shimazu en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HinotsuShiro en-aut-sei=Hinotsu en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UchitomiYosuke en-aut-sei=Uchitomi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=InagakiMasatoshi en-aut-sei=Inagaki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Medical Development Field, Okayama University 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=Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=4 en-affil=Division of Health Services Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=5 en-affil=Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=6 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=7 en-affil=Department of Medical Informatics, Shimane University Hospital kn-affil= affil-num=8 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Medical Development Field, Okayama University kn-affil= affil-num=10 en-affil=Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=11 en-affil=Department of Biostatistics and Data Management, Sapporo Medical University kn-affil= affil-num=12 en-affil=Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine kn-affil= affil-num=13 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=healthcare disparities kn-keyword=healthcare disparities en-keyword=psycho-oncology kn-keyword=psycho-oncology en-keyword=schizophrenia spectrum disorders kn-keyword=schizophrenia spectrum disorders END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=e70285 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cardiogenic cerebral infarction after Takotsubo cardiomyopathy in a patient with catatonia: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Takotsubo cardiomyopathy (TTC) is a transient cardiac condition often triggered by an emotional or physical stress. TTC usually has a benign clinical course with full recovery. However, in rare cases, TTC is complicated by cardiogenic shock, left ventricular rupture, or ventricular thrombus. We report a case of a patient with catatonia who developed TTC and subsequently experienced extensive cerebral infarction.
Case Presentation: A 71-year-old woman with no prior psychiatric history was admitted for catatonia following a suicide attempt. During hospitalization, she exhibited electrocardiography (ECG) abnormalities and elevated D-dimer levels. Transthoracic echocardiography revealed apical hypokinesis and basal hyperkinesis, consistent with TTC, along with an intraventricular thrombus. Cardiovascular CT angiography confirmed normal coronary arteries. She was diagnosed with TTC complicated by left ventricular thrombus and deep vein thrombosis. Anticoagulant therapy was initiated. Despite improvement in catatonia with lorazepam, she developed right hemiplegia and aphasia on Day 5 due to cardiogenic cerebral infarction from thromboembolism. Thrombolytic therapy was not indicated, and conservative treatment was provided. Although cardiac function normalized by Day 16, she was left with severe neurological deficits.
Conclusion: The case highlights the diagnostic challenges of TTC in non-communicative psychiatric patients and the potential for severe complications. Psychiatrists need to be aware of the development of TTC as a serious physical complication in patients with catatonia. en-copyright= kn-copyright= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KodamaMasafumi en-aut-sei=Kodama en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Medical Development Field, Okayama University 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 General Internal Medicine 3, Kawasaki Medical School General Medical Center kn-affil= affil-num=4 en-affil=Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Okayama Psychiatric Medical Center kn-affil= en-keyword=catatonia kn-keyword=catatonia en-keyword=cerebral infarction kn-keyword=cerebral infarction en-keyword=depression kn-keyword=depression en-keyword=Takotsubo cardiomyopathy kn-keyword=Takotsubo cardiomyopathy en-keyword=ventricular thrombus kn-keyword=ventricular thrombus END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=1 article-no= start-page=10 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251218 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gut microbial metabolite butyrate boosts p53-expressing telomerase-specific oncolytic adenovirus efficacy by enhancing infectivity and activating MHC-I/cGAS-STING en-subtitle= kn-subtitle= en-abstract= kn-abstract=The gut microbiota plays an essential role in regulating host immunity, and its metabolites such as butyrate exert immunomodulatory effects by acting as histone deacetylase inhibitors. Oncolytic virotherapy has emerged as a promising approach for cancer treatment, and we have developed OBP-702, a telomerase-specific oncolytic adenovirus that expresses p53 and elicits strong systemic antitumor responses. In this study, the potential synergy between butyrate and OBP-702 was investigated in colorectal cancer models. Using human and murine colorectal carcinoma cell lines, butyrate was found to directly enhance the infectivity of OBP-702 by upregulating CAR and integrins, thereby promoting apoptosis and autophagy in tumor cells. In addition, butyrate indirectly boosted systemic antitumor immunity by upregulating MHC-I expression through activation of the cGAS-STING pathway and enhancing CD8 + T cell recruitment via CXCL10 secretion. These findings were supported by in vivo experiments using CT26 subcutaneous, bilateral, and orthotopic tumor models, in which the combination of oral butyrate and intratumoral OBP-702 administration produced synergistic antitumor effects. These results highlight the therapeutic potential of integrating gut microbial metabolites with oncolytic virotherapy as a novel immunotherapeutic strategy for colorectal cancer. en-copyright= kn-copyright= en-aut-name=SakamotoMasaki en-aut-sei=Sakamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatayamaTetsuya en-aut-sei=Katayama en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MikaneYu en-aut-sei=Mikane en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HanzawaShunya en-aut-sei=Hanzawa en-aut-mei=Shunya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KadowakiDaisuke en-aut-sei=Kadowaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=HamadaYuki en-aut-sei=Hamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoRyoma en-aut-sei=Sugimoto en-aut-mei=Ryoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YagiChiaki en-aut-sei=Yagi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Butyrate kn-keyword=Butyrate en-keyword=Oncolytic adenovirus kn-keyword=Oncolytic adenovirus en-keyword=MHC-I kn-keyword=MHC-I en-keyword=CD8 + T cells kn-keyword=CD8 + T cells en-keyword=Cancer immunotherapy kn-keyword=Cancer immunotherapy END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=20 article-no= start-page=4309 end-page=4317 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251009 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characterization of Autonomous and Ca2+/Calmodulin-Dependent Activities of CaMKK Isoforms In Vitro and in Mouse Tissues en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ca2+/CaM-dependent protein kinase kinase (CaMKK) phosphorylates and activates downstream kinases, including CaMKI, CaMKIV, PKB, and AMPK, regulating various cellular functions such as neuronal morphogenesis, metabolic control, and pathophysiological pathways, such as cancer progression. CaMKKα/1 is tightly regulated by an autoinhibitory mechanism. CaMKKβ/2 activity is highly Ca2+/CaM-independent (autonomous activity) in vitro and Ca2+/CaM-dependent in cultured cells. Whether these two activity states of CaMKKβ/2 exist in vivo and the detailed regulatory mechanisms for the transition of both activity states remain unclear due to the difficulty in distinguishing the two activity states. In this study, we detected Ca2+-dependent and autonomous CaMKK activity in HeLa cells and successfully separated both activity states of CaMKKβ/2 in mouse brain and testis extracts using a recently developed CaMKK inhibitor (TIM-063)-coupled sepharose, which binds to the catalytic domain in the active state but not in the autoinhibited state. Furthermore, lambda protein phosphatase treatment converted the Ca2+/CaM-dependent form to the autonomous form of CaMKKβ/2, which was not affected by Ala mutation of Ser128, Ser132, and Ser136. The two activity forms of CaMKKβ/2 had equivalent Ca2+/CaM-binding ability. The findings demonstrate the presence of autonomous and Ca2+/CaM-dependent forms of CaMKKβ/2 independently in mouse tissues and cultured cells. The transition of these states of CaMKKβ/2 may be dynamically regulated by the phosphorylation/dephosphorylation of serine residues in the N-terminal regulatory domain. en-copyright= kn-copyright= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenYerun en-aut-sei=Chen en-aut-mei=Yerun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=IshikawaTeruhiko en-aut-sei=Ishikawa en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakagamiHiroyuki en-aut-sei=Sakagami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=5 en-affil=Department of Anatomy, Kitasato University School of Medicine kn-affil= affil-num=6 en-affil=Clinical Examination Department, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=7 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=1 article-no= start-page=012041 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High-quality welding of copper and aluminum by angled laser irradiation and insert metals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Copper is an important material in order to use electricity effectively, and aluminum is also an attractive material to perform lightweight construction. Laser welding of copper and aluminum is required, and there are some reports to weld copper and aluminum firmly by laser irradiation from the aluminum side. On the other hand, laser irradiation from the copper side requires high power density to generate a keyhole, which causes the strong convection of molten aluminum into copper. Thus, brittle intermetallic compounds with rich aluminum result in the deterioration of joining strength. Angled laser irradiation enables mild heat input to the aluminum side, and the combination of angled and superposed irradiation of blue and near-infrared (NIR) lasers achieved a remarkable increase of breaking strength. However, the breaking strength is still lower than the base materials. Therefore, insert materials between copper and aluminum plates were investigated by the angled irradiation of blue and NIR lasers from the copper side. The breaking strength with insert materials showed higher values in the order of titanium mesh, nickel foil, and nickel mesh, and its value with the nickel mesh was close to the tensile strength of aluminum in a cross tensile test. Further improvement of breaking strength is possible by inserting the nickel mesh between copper and aluminum plates in the case of angled irradiation of blue and NIR lasers even from the copper side. en-copyright= kn-copyright= en-aut-name=OkamotoYasuhiro en-aut-sei=Okamoto en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaYuki en-aut-sei=Yamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaAkira en-aut-sei=Okada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyakeMasaki en-aut-sei=Miyake en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamuraTakeshi en-aut-sei=Yamamura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagasakiKatsutoshi en-aut-sei=Nagasaki en-aut-mei=Katsutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiNorio en-aut-sei=Nishi en-aut-mei=Norio 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 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=Kataoka Corporation kn-affil= affil-num=5 en-affil=Kataoka Corporation kn-affil= affil-num=6 en-affil=Kataoka Corporation kn-affil= affil-num=7 en-affil=Kataoka Corporation kn-affil= en-keyword=welding kn-keyword=welding en-keyword=copper kn-keyword=copper en-keyword=aluminum kn-keyword=aluminum en-keyword=insert metal kn-keyword=insert metal en-keyword=intermetallic compound kn-keyword=intermetallic compound en-keyword=fiber laser kn-keyword=fiber laser en-keyword=blue laser kn-keyword=blue laser en-keyword=angled irradiation kn-keyword=angled irradiation END start-ver=1.4 cd-journal=joma no-vol=53 cd-vols= no-issue=22 article-no= start-page=gkaf1322 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=eIF2D promotes 40S ribosomal subunit recycling during intrinsic ribosome destabilization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although eukaryotic initiation factor 2D (eIF2D) is implicated in translation initiation, reinitiation, and ribosome recycling, its precise role remains unclear. Here, we show that eIF2D promotes 40S ribosome recycling during intrinsic ribosome destabilization (IRD), a process in which ribosomes stochastically destabilize while translating proteins with consecutive acidic amino acids at their NH2-terminus. Unrecycled 40S ribosomes accumulate in eIF2D-deficient cells, leading to 80S ribosome stalling. Selective translation complex profiling (TCP-seq) reveals that eIF2D preferentially associates with IRD-prone regions. The winged helix domain, unique to eIF2D but absent in MCTS1–DENR, enhances its binding to 40S subunits, but likely clashes with ABCE1 during stop-codon-associated recycling. Loss of eIF2D reduces the expression of IRD-inducing proteins, including splicing factors. Together, these findings define a previously unappreciated role for eIF2D in 40S recycling and clarify its mechanistic divergence from the MCTS1–DENR complex. en-copyright= kn-copyright= en-aut-name=IchiharaKazuya en-aut-sei=Ichihara en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiraishiTaichi en-aut-sei=Shiraishi en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChadaniYuhei en-aut-sei=Chadani en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitoYuki en-aut-sei=Kito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShiraishiChisa en-aut-sei=Shiraishi en-aut-mei=Chisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirataMina en-aut-sei=Hirata en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KoboAkinao en-aut-sei=Kobo en-aut-mei=Akinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HatanoAtsushi en-aut-sei=Hatano en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsumotoMasaki en-aut-sei=Matsumoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MachidaKodai en-aut-sei=Machida en-aut-mei=Kodai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ImatakaHiroaki en-aut-sei=Imataka en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=Mishiro-SatoEmi en-aut-sei=Mishiro-Sato en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NojimaTakayuki en-aut-sei=Nojima en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ItoTakuhiro en-aut-sei=Ito en-aut-mei=Takuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TaguchiHideki en-aut-sei=Taguchi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakayamaKeiichi I en-aut-sei=Nakayama en-aut-mei=Keiichi I kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MatsumotoAkinobu en-aut-sei=Matsumoto en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=2 en-affil=Division of Biological Science, Graduate School of Science, Nagoya 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=Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University kn-affil= affil-num=5 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=6 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=7 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=8 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=9 en-affil=Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=10 en-affil=Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=11 en-affil=Graduate School of Engineering, University of Hyogo kn-affil= affil-num=12 en-affil=Graduate School of Engineering, University of Hyogo kn-affil= affil-num=13 en-affil=Advanced Genomics Center, National Institute of Genetics kn-affil= affil-num=14 en-affil=Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University kn-affil= affil-num=15 en-affil=Medical Institute of Bioregulation, Kyushu University kn-affil= affil-num=16 en-affil=Laboratory for Translation Structural Biology, RIKEN Center for Integrative Medical Sciences kn-affil= affil-num=17 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=18 en-affil=Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University kn-affil= affil-num=19 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=3 article-no= start-page=e220018 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=Origin of the unique topology of the triangular water cluster in <i>Rubrobacter xylanophilus</i> rhodopsin en-subtitle= kn-subtitle= en-abstract= kn-abstract=The crystal structure of Rubrobacter xylanophilus rhodopsin (RxR) reveals a triangular cluster of three water molecules (W413, W415, and W419) at the extracellular proton-release site, near Glu187 and Glu197. Using a quantum mechanical/molecular mechanical approach, we identified the structural nature of this unique water cluster. The triangular shape is best reproduced when all three water molecules are neutral H2O with protonated Glu187 and deprotonated Glu197. Attempts to place H3O+ at any of these water molecules result in spontaneous proton transfer to one of the acidic residues and significant distortion from the crystal structure. The plane defined by the triangular water cluster extends into the guanidinium plane of Arg71, with both aligned along the W413...W419 axis. This extended plane lies nearly perpendicular to a five-membered, ring-like H-bond network involving two carboxyl oxygen atoms from Glu187 and one from Glu197. The resulting bipartite planar architecture, defined by the water triangle, Arg71, and the Glu187/Glu197 network may reflect the exceptional thermal stability in RxR. en-copyright= kn-copyright= en-aut-name=NojiTomoyasu en-aut-sei=Noji en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujimuraMasaki en-aut-sei=Tsujimura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoKeisuke en-aut-sei=Saito en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=IshikitaHiroshi en-aut-sei=Ishikita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Advanced Interdisciplinary Studies, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=4 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=microbial rhodopsin kn-keyword=microbial rhodopsin en-keyword=proton transfer pathway kn-keyword=proton transfer pathway en-keyword=H3O+ kn-keyword=H3O+ en-keyword=pKa kn-keyword=pKa en-keyword=proton release group kn-keyword=proton release group END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=e70144 end-page= 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=Japanese Multi‐Institution Study of Success Rates of Wire‐Guided Biliary Cannulation During Endoscopic Retrograde Cholangiopancreatography in Relation to Guidewire tip Length (JMIT Study) (With Video) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Wire-guided cannulation (WGC) reportedly increases the successful biliary cannulation rate and reduces the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. Currently, various types of guidewires are available. However, the effect of the length of flexible-tip guidewires on the success rate of biliary cannulation under WGC and the rate of adverse events, especially post-endoscopic retrograde cholangiopancreatography pancreatitis, is unclear. The aim of this study was to compare the influence of long-tapered and short-tapered tips of a 0.025-inch guidewire on outcomes in primary selective biliary cannulation.
Methods: Consecutive patients who underwent biliary access under endoscopic retrograde cholangiopancreatography guidance using WGC at 27 high-volume centers in Japan were enrolled in this prospective registration study. The primary outcome was the technical success rate of biliary cannulation. The secondary outcomes were the rates of adverse events, biliary cannulation time, and number of guidewire insertions into the pancreatic duct.
Results: A total of 530 patients underwent biliary cannulation for biliary disease with native papilla between April 2021 and December 2023. The technical success rate of biliary cannulation was 86.1% (161/187) in the long-tip group and 84.3% (289/343) in the short-tip group, indicating no significant differences between the two groups. Although the frequency of post-endoscopic retrograde cholangiopancreatography was not significantly different, the successful biliary cannulation rate without guidewire mis-insertion into the main pancreatic duct was significantly higher in the long tip group (64.7%, 121/187) compared with the short tip group (54.2%, 186/343p = 0.02).
Conclusions: In conclusion, WGC using long-tip guidewires might reduce the risk of guidewire insertion into the main pancreatic duct. en-copyright= kn-copyright= en-aut-name=OguraTakeshi en-aut-sei=Ogura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanisakaYuki en-aut-sei=Tanisaka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SekineMasanari en-aut-sei=Sekine en-aut-mei=Masanari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiKatsumasa en-aut-sei=Kobayashi en-aut-mei=Katsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaruyamaHirotsugu en-aut-sei=Maruyama en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HiraiShinji en-aut-sei=Hirai en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShiomiHideyuki en-aut-sei=Shiomi en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShigekawaMinoru en-aut-sei=Shigekawa en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuwataniMasaki en-aut-sei=Kuwatani en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IkezawaKenji en-aut-sei=Ikezawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ItonagaMasahiro en-aut-sei=Itonaga en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakenakaMamoru en-aut-sei=Takenaka en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HijiokaSusumu en-aut-sei=Hijioka en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IkeuraTsukasa en-aut-sei=Ikeura en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=DoiShinpei en-aut-sei=Doi en-aut-mei=Shinpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujimoriNao en-aut-sei=Fujimori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KoizumiKazuya en-aut-sei=Koizumi en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakaiYousuke en-aut-sei=Nakai en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=InoueTadahisa en-aut-sei=Inoue en-aut-mei=Tadahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MukaiShuntaro en-aut-sei=Mukai en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MinamiRyuki en-aut-sei=Minami en-aut-mei=Ryuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MandaiKoichiro en-aut-sei=Mandai en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MatsudaAtsuhiro en-aut-sei=Matsuda en-aut-mei=Atsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=IwashitaTakuji en-aut-sei=Iwashita en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KawashimaHiroki en-aut-sei=Kawashima en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ItoiTakao en-aut-sei=Itoi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Endoscopy Center, Osaka Medical and Pharmaceutical University kn-affil= affil-num=2 en-affil=Gastroenterology, Saitama Medical University International Medical Center kn-affil= affil-num=3 en-affil=Department of Gastroenterology Jichi Medical University, Saitama Medical Center kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Tokyo Metropolitan Bokutoh Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=6 en-affil=Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Division of Hepatobiliary and Pancreatic Diseases, Hyogo Medical University kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Hokkaido University Hospital kn-affil= affil-num=10 en-affil=Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute kn-affil= affil-num=11 en-affil=Second Department of Internal Medicine, Wakayama Medical University kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University kn-affil= affil-num=13 en-affil=Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital kn-affil= affil-num=14 en-affil=Third Department of Internal Medicine, Kansai Medical University kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Teikyo University Mizonokuchi Hospital kn-affil= affil-num=16 en-affil=Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=17 en-affil=Department of Gastroenterology, Medicine Center, Shonan Kamakura General Hospital kn-affil= affil-num=18 en-affil=Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=19 en-affil=Department of Gastroenterology, Aichi Medical University kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Tokyo Medical University kn-affil= affil-num=21 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Gastroenterology, Tenri Hospital kn-affil= affil-num=23 en-affil=Department of Gastroenterology, Kyoto Second Red Cross Hospital kn-affil= affil-num=24 en-affil=Department of Internal Medicine, Toyama Prefectural Central Hospital kn-affil= affil-num=25 en-affil=First Department of Internal Medicine, Gifu University Hospital kn-affil= affil-num=26 en-affil=Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=27 en-affil=Department of Gastroenterology and Hepatology, Tokyo Medical University kn-affil= en-keyword=ERCP kn-keyword=ERCP en-keyword=guidewire kn-keyword=guidewire en-keyword=pancreatitis kn-keyword=pancreatitis en-keyword=post-ERCP pancreatitis kn-keyword=post-ERCP pancreatitis en-keyword=wire-guided cannulation kn-keyword=wire-guided cannulation END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=12 article-no= start-page=1584 end-page=1595 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.
Methods: This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups.
Results: This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55–1.17) and 0.55 for PFS (95% CI 0.38–0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42–1.29) and 0.79 for PFS (95% CI 0.42–1.49).
Conclusions: GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC. en-copyright= kn-copyright= en-aut-name=KobayashiSatoshi en-aut-sei=Kobayashi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakachiKohei en-aut-sei=Nakachi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoKouji en-aut-sei=Yamamoto en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UenoMakoto en-aut-sei=Ueno en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MarukiYuta en-aut-sei=Maruki en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkezawaKenji en-aut-sei=Ikezawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TerashimaTakeshi en-aut-sei=Terashima en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuSatoshi en-aut-sei=Shimizu en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OshimaKotoe en-aut-sei=Oshima en-aut-mei=Kotoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujiKunihiro en-aut-sei=Tsuji en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasakiYoshiharu en-aut-sei=Masaki en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsumuraHidetaka en-aut-sei=Tsumura en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShibukiTaro en-aut-sei=Shibuki en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OzakaMasato en-aut-sei=Ozaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OkanoNaohiro en-aut-sei=Okano en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkamuraYukiyasu en-aut-sei=Okamura en-aut-mei=Yukiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UmemotoKumiko en-aut-sei=Umemoto en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SatohTatsunori en-aut-sei=Satoh en-aut-mei=Tatsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KojimaYasushi en-aut-sei=Kojima en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ShiojiKazuhiko en-aut-sei=Shioji en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NebikiHiroko en-aut-sei=Nebiki en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=DoiToshifumi en-aut-sei=Doi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NaganumaAtsushi en-aut-sei=Naganuma en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KataokaShigeki en-aut-sei=Kataoka en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KitaEmiri en-aut-sei=Kita en-aut-mei=Emiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=AsamaHiroyuki en-aut-sei=Asama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TsuchiyaKaoru en-aut-sei=Tsuchiya en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=UnnoMichiaki en-aut-sei=Unno en-aut-mei=Michiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=AshidaReiko en-aut-sei=Ashida en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=OhnoIzumi en-aut-sei=Ohno en-aut-mei=Izumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=ItoiTakao en-aut-sei=Itoi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=NegoroYuji en-aut-sei=Negoro en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=SakamotoYasunari en-aut-sei=Sakamoto en-aut-mei=Yasunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=ArimaShiho en-aut-sei=Arima en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=AsagiAkinori en-aut-sei=Asagi en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=OkuyamaHiroyuki en-aut-sei=Okuyama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=KomatsuYoshito en-aut-sei=Komatsu en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=KobayashiNoritoshi en-aut-sei=Kobayashi en-aut-mei=Noritoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=NaganoHiroaki en-aut-sei=Nagano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=FuruseJunji en-aut-sei=Furuse en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Tochigi Cancer Center kn-affil= affil-num=3 en-affil=Department of Biostatistics, Yokohama City University School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Kanazawa University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Kanazawa University Hospital kn-affil= affil-num=9 en-affil=Division of Gastrointestinal Oncology, Shizuoka Cancer Center kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Ishikawa Prefectural Central Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine kn-affil= affil-num=12 en-affil=Department of Gastroenterological Oncology, Hyogo Cancer Center kn-affil= affil-num=13 en-affil=Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East kn-affil= affil-num=14 en-affil=Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=15 en-affil=Department of Medical Oncology, Kyorin University Faculty of Medicine kn-affil= affil-num=16 en-affil=Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine kn-affil= affil-num=17 en-affil=Department of Clinical Oncology, St. Marianna University School of Medicine kn-affil= affil-num=18 en-affil=Department of Gastroenterology, Shizuoka General Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterology, National Center for Global Health and Medicine kn-affil= affil-num=20 en-affil=Department of Gastroenterology, Niigata Cancer Center Hospital kn-affil= affil-num=21 en-affil=Department of Gastroenterology, Osaka City General Hospital kn-affil= affil-num=22 en-affil=Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine kn-affil= affil-num=23 en-affil=Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center kn-affil= affil-num=24 en-affil=Department of Clinical Oncology, Graduate School of Medicine Faculty of Medicine, Kyoto University kn-affil= affil-num=25 en-affil=Department of Gastroenterology, Chiba Cancer Center kn-affil= affil-num=26 en-affil=Department of Gastroenterology, Fukushima Medical University kn-affil= affil-num=27 en-affil=Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital kn-affil= affil-num=28 en-affil=Department of Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=29 en-affil=Second Department of Internal Medicine, Wakayama Medical University kn-affil= affil-num=30 en-affil=Department of Gastroenterology, Okayama University Graduate School of Medicine kn-affil= affil-num=31 en-affil=Department of Gastroenterology, Chiba University Graduate School of Medicine kn-affil= affil-num=32 en-affil=Department of Gastroenterology, Tokyo Medical University kn-affil= affil-num=33 en-affil=Department of Oncologial Medicine, Kochi Health Sciences Center kn-affil= affil-num=34 en-affil=Department of Gastroenterology and Hepatology, International University of Health and Welfare Atami Hospital kn-affil= affil-num=35 en-affil=Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=36 en-affil=Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=37 en-affil=Department of Medical Oncology, Kagawa University Hospital kn-affil= affil-num=38 en-affil=Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center kn-affil= affil-num=39 en-affil=Department of Oncology, School of Medicine Graduate School of Medicine, Yokohama City University kn-affil= affil-num=40 en-affil=Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine kn-affil= affil-num=41 en-affil=Department of Gastroenterology, Kanagawa Cancer Center kn-affil= en-keyword=Biliary tract cancer kn-keyword=Biliary tract cancer en-keyword=Unresectable kn-keyword=Unresectable en-keyword=Chemotherapy kn-keyword=Chemotherapy en-keyword=Older kn-keyword=Older en-keyword=Survival kn-keyword=Survival 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=20251118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mortality and cancer risk in patients with chronic pancreatitis in japan: insights into the importance of surveillance for pancreatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objective: Since the 2010s, Japan’s national health insurance system has covered key management for chronic pancreatitis (CP), including pancreatic enzyme replacement therapy. These therapies are expected to improve long-term prognosis; however, recent data are lacking. This study aimed to clarify the updated cancer risk and mortality among patients with CP in Japan.
Methods: We conducted a multicenter, retrospective cohort study on 1,110 patients with CP treated at 28 institutions in 2011. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated for comorbidities. Factors associated with the development of malignancy and overall survival were analyzed.
Results: Patients with CP had an elevated SIR of 1.62 (95% confidence interval [CI], 1.43–1.83) for malignancy, with the highest risk observed for pancreatic cancer (SIR = 6.44 [95% CI, 4.64–8.90]). During follow-up, 143 patients (12.9%) died, most frequently from malignancy (47.5%). The SMR was elevated in all patients with CP (SMR = 1.20 [95% CI, 1.01–1.42]) and in those with alcohol-related CP (SMR = 1.49 [95% CI, 1.23–1.81]) but not in those with alcohol-unrelated CP. Pancreatic cancer was identified as the strongest factor associated with overall survival (hazard ratio, 48.92 in multivariate analysis). Overall survival of the patients with pancreatic cancer was significantly longer in those who underwent regular examinations for CP at least every three months (P = 0.011).
Conclusions: Patients with alcohol-related CP have higher mortality than the general population in Japan. Pancreatic cancer remains a crucial prognostic factor in patients with CP. Regular surveillance for pancreatic cancer is important to improve their prognosis. en-copyright= kn-copyright= en-aut-name=MatsumotoRyotaro en-aut-sei=Matsumoto en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikutaKazuhiro en-aut-sei=Kikuta en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakikawaTetsuya en-aut-sei=Takikawa en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaiYousuke en-aut-sei=Nakai en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakenakaMamoru en-aut-sei=Takenaka en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkiKentaro en-aut-sei=Oki en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhnoEizaburo en-aut-sei=Ohno en-aut-mei=Eizaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoKen en-aut-sei=Ito en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujimoriNao en-aut-sei=Fujimori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatanumaAkio en-aut-sei=Katanuma en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasudaAtsuhiro en-aut-sei=Masuda en-aut-mei=Atsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HoriYasuki en-aut-sei=Hori en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IkeuraTsukasa en-aut-sei=Ikeura en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SuzukiRei en-aut-sei=Suzuki en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamamotoSatoshi en-aut-sei=Yamamoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SogameYoshio en-aut-sei=Sogame en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawashimaHiroki en-aut-sei=Kawashima en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ItoTetsuhide en-aut-sei=Ito en-aut-mei=Tetsuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OkuwakiKosuke en-aut-sei=Okuwaki en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ItoiTakao en-aut-sei=Itoi en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TakayamaYukiko en-aut-sei=Takayama en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=NakamuraAkira en-aut-sei=Nakamura en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TeraiShuji en-aut-sei=Terai en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KuwataniMasaki en-aut-sei=Kuwatani en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KishiwadaMasashi en-aut-sei=Kishiwada en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ShigekawaMinoru en-aut-sei=Shigekawa en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MatsumoriTomoaki en-aut-sei=Matsumori en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=InatomiOsamu en-aut-sei=Inatomi en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HattaWaku en-aut-sei=Hatta en-aut-mei=Waku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=IrisawaAtsushi en-aut-sei=Irisawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=UnnoMichiaki en-aut-sei=Unno en-aut-mei=Michiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=TakeyamaYoshifumi en-aut-sei=Takeyama en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MasamuneAtsushi en-aut-sei=Masamune en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=Japan Pancreatitis Study Group for Chronic Pancreatitis en-aut-sei=Japan Pancreatitis Study Group for Chronic Pancreatitis en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= affil-num=1 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine kn-affil= affil-num=8 en-affil=Division of Gastroenterology and Hepatology, Toho University Omori Medical Center kn-affil= affil-num=9 en-affil=Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Center for Gastroenterology, Teine-Keijinkai Hospital kn-affil= affil-num=11 en-affil=Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Kansai Medical University kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Fukushima Medical University School of Medicine kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Fujita Health University Bantane Hospital kn-affil= affil-num=16 en-affil=Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare kn-affil= affil-num=19 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Tokyo Medical University kn-affil= affil-num=21 en-affil=Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University kn-affil= affil-num=22 en-affil=Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine kn-affil= affil-num=23 en-affil=Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=24 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Gastroenterology and Hepatology, Hokkaido University Hospital kn-affil= affil-num=26 en-affil=Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine kn-affil= affil-num=27 en-affil=Department of Gastroenterology and Hepatology, The University of Osaka Graduate School of Medicine kn-affil= affil-num=28 en-affil=Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine kn-affil= affil-num=29 en-affil=Department of Medicine, Shiga University of Medical Science kn-affil= affil-num=30 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=31 en-affil=Department of Gastroenterology, Dokkyo Medical University School of Medicine kn-affil= affil-num=32 en-affil=Department of Surgery, Tohoku University Graduate School of Medicine kn-affil= affil-num=33 en-affil=Department of Surgery, Kindai University Faculty of Medicine kn-affil= affil-num=34 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=35 en-affil= kn-affil= en-keyword=Alcohol kn-keyword=Alcohol en-keyword=Chronic pancreatitis kn-keyword=Chronic pancreatitis en-keyword=Pancreatic cancer kn-keyword=Pancreatic cancer en-keyword=Pancreatitis kn-keyword=Pancreatitis en-keyword=Smoking kn-keyword=Smoking END start-ver=1.4 cd-journal=joma no-vol=191 cd-vols= no-issue= article-no= start-page=107586 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Experimental approach of internal dose map visualization during helical CT examinations: importance of X-ray incident direction analysis and central internal dose estimation en-subtitle= kn-subtitle= en-abstract= kn-abstract=During computed tomography (CT) examination, radiation exposures should be appropriately managed taking into considering the effects of bowtie filter, the heel effect and over-beaming effect. Furthermore, the analysis of an X-ray incident direction is important. The purpose of this study is to develop a procedure to obtain two-dimensional (2D) internal dose distributions based on actual measurements of surface dose distribution and central internal dose data. Experiments were conducted using a clinical CT scanner and four cylindrical polyacetal resin (POM) phantoms having diameters of 15–30 cm. The entrance surface doses and the central internal dose were measured by placing the optically stimulated luminescence (OSL) dosimeters on the surface and inner part of the phantom, respectively, during helical CT scans. The X-ray incident direction at the slice containing the dosimeter was estimated based on the noise distribution analysis of the CT image. Then, circumferential surface dose distributions were determined as a function of the X-ray incident direction. Based on these experimental data, we succeeded in visualizing the 2D dose distributions. The obtained dose distribution was inhomogeneous, clearly reflecting the influence of factors such as the heel effect. The uncertainty due to our methodology was estimated to be from 4.3 % to 7.4 %. Our methodology needs central internal dose data, and the absence of this data introduced additional systematic uncertainties of +6.9 % to −11.4 %. In conclusion, correcting for the effect of the X-ray incident directions for entrance surface dose and adding the central inner dose data can improve the reliability of the internal dose distribution. en-copyright= kn-copyright= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakegamiKazuki en-aut-sei=Takegami en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiDaiki en-aut-sei=Kobayashi en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoSota en-aut-sei=Goto en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakemitsuMasaki en-aut-sei=Takemitsu en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiiRin en-aut-sei=Ishii en-aut-mei=Rin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorimotoShinichi en-aut-sei=Morimoto en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MakiMotochika en-aut-sei=Maki en-aut-mei=Motochika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Yamaguchi University Hospital kn-affil= affil-num=3 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=4 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=5 en-affil=Faculty of Health Sciences, Kobe Tokiwa University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=8 en-affil=Department of Radiological Technology, Yamaguchi University Hospital kn-affil= affil-num=9 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= affil-num=10 en-affil=Meditec Japan Co., Ltd. kn-affil= affil-num=11 en-affil=Meditec Japan Co., Ltd. kn-affil= en-keyword=Computed tomography kn-keyword=Computed tomography en-keyword=Medical dosimetry kn-keyword=Medical dosimetry en-keyword=Internal dose distribution kn-keyword=Internal dose distribution en-keyword=X-ray incident direction kn-keyword=X-ray incident direction en-keyword=Optically stimulated luminescence dosimeter kn-keyword=Optically stimulated luminescence dosimeter END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=38590 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oncolytic adenoviruses replicate selectively in tumor cells and induce immunogenic cell death, but predictive biomarkers for early therapeutic response are lacking. This study evaluated extracellular vesicle-encapsulated adenoviral E1A-DNA (EV-E1A-DNA) as a minimally invasive biomarker for monitoring responses to telomerase-specific oncolytic adenoviruses OBP-301 and OBP-502. EVs were isolated from human and murine cancer cell lines and from the serum of treated mice using ultracentrifugation. EV-associated E1A-DNA levels were measured by quantitative polymerase chain reaction and found to correlate with cytotoxicity in vitro and tumor regression in vivo. In xenograft models, serum EV-E1A-DNA levels at 2 days post-treatment showed strong correlations with final tumor volume and survival, supporting their utility as an early predictive biomarker. In immunocompetent mice pre-immunized with wild-type adenovirus, free viral DNA was undetectable in serum due to neutralizing antibodies, whereas EV-E1A-DNA remained detectable. This “stealth effect” indicates that EVs protect viral components from immune clearance. These results demonstrate that EV-E1A-DNA is a sensitive and virus-specific biomarker that enables early assessment of therapeutic efficacy, even in the presence of antiviral immunity. This strategy offers a promising liquid biopsy approach for personalized monitoring of oncolytic virotherapy and may be applicable to other virus-based therapies. en-copyright= kn-copyright= en-aut-name=YagiChiaki en-aut-sei=Yagi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HanzawaShunya en-aut-sei=Hanzawa en-aut-mei=Shunya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KadowakiDaisuke en-aut-sei=Kadowaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakamotoMasaki en-aut-sei=Sakamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamadaYuki en-aut-sei=Hamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoRyoma en-aut-sei=Sugimoto en-aut-mei=Ryoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhtaniTomoko en-aut-sei=Ohtani en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KumonKento en-aut-sei=Kumon en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Oncolytic adenovirus kn-keyword=Oncolytic adenovirus en-keyword=Extracellular vesicle kn-keyword=Extracellular vesicle en-keyword=Liquid biopsy kn-keyword=Liquid biopsy en-keyword=Predictive biomarker kn-keyword=Predictive biomarker en-keyword=Stealth effect kn-keyword=Stealth effect END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=17 article-no= start-page=6122 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250829 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Potential of Kidney Exchange Programs (KEPs) in Japan for Donor-Specific Antibody-Positive Kidney Transplants: A Questionnaire Survey on KEPs and a Multi-Institutional Study Conducting Virtual Cross-Matching Simulations en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To clarify the need for a kidney exchange program (KEP) in Japan by conducting a questionnaire survey on KEPs and simulated KEPs by virtual cross-matching based on past cases of transplantation avoidance. Methods: In addition to the content regarding KEPs, an electronic survey was conducted to investigate the number of cases of kidney transplant abandonment due to “immunological” reasons over the past 10 years (2012–2021). Virtual cross-matching was conducted to simulate the feasibility of avoiding immunological risks and enabling kidney transplantation in patients who were previously unable to undergo the procedure. Results: The survey received responses from 107 facilities (response rate: 81.7%). In response to the question about the necessity of a KEP in Japan, 71 facilities (66.4%) indicated that KEPs are necessary. In addition, 251 living-donor kidney transplants were abandoned for “immunological” reasons over the past decade (2012–2021). Among the 80 pairs for which detailed information was available, virtual cross-matching simulations showed that 37/80 pairs (46.3%) were donor-specific antibody (DSA)-negative for blood type-matched combinations, and 41/80 pairs (51.3%) were DSA-negative for blood type-incompatible transplants. Conclusions: The need for a KEP in Japan and its potential usefulness were demonstrated. en-copyright= kn-copyright= en-aut-name=ItoTaihei en-aut-sei=Ito en-aut-mei=Taihei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoMiki en-aut-sei=Ito en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AidaNaohiro en-aut-sei=Aida en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuriharaKei en-aut-sei=Kurihara en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TeraoAkihiro en-aut-sei=Terao en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WataraiYoshihiko en-aut-sei=Watarai en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoMitsuru en-aut-sei=Saito en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KakuKeizo en-aut-sei=Kaku en-aut-mei=Keizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiiDaisuke en-aut-sei=Ishii en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SekiguchiSatoshi en-aut-sei=Sekiguchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YonedaTatsuo en-aut-sei=Yoneda en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UnagamiKohei en-aut-sei=Unagami en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TasakiMasayuki en-aut-sei=Tasaki en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwamotoHitoshi en-aut-sei=Iwamoto en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakahashiKazuhiro en-aut-sei=Takahashi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamanakaKazuaki en-aut-sei=Yamanaka en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SugimotoMikio en-aut-sei=Sugimoto en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NishikawaKouhei en-aut-sei=Nishikawa en-aut-mei=Kouhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SetoChikashi en-aut-sei=Seto en-aut-mei=Chikashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MuramatsuMasaki en-aut-sei=Muramatsu en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=AsaiToshihiro en-aut-sei=Asai en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=IwamiDaiki en-aut-sei=Iwami en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=YamadaYasutoshi en-aut-sei=Yamada en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=YamanagaShigeyoshi en-aut-sei=Yamanaga en-aut-mei=Shigeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KomatsuTomonori en-aut-sei=Komatsu en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MiuraMasayoshi en-aut-sei=Miura en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NoharaTakahiro en-aut-sei=Nohara en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=MaruyamaMichihiro en-aut-sei=Maruyama en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=MiyauchiYuki en-aut-sei=Miyauchi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=TanakaToshiaki en-aut-sei=Tanaka en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=NakamuraMichio en-aut-sei=Nakamura en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=HottaKiyohiko en-aut-sei=Hotta en-aut-mei=Kiyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KenmochiTakashi en-aut-sei=Kenmochi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=2 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=3 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=4 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=5 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= affil-num=6 en-affil=Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital kn-affil= affil-num=7 en-affil=Division of Blood Purification, Akita University Hospital kn-affil= affil-num=8 en-affil=Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Urology, Kitasato University of Medicine kn-affil= affil-num=10 en-affil=Transplantation Surgery, Japan Community Healthcare Organization Sendai Hospital kn-affil= affil-num=11 en-affil=Unit of Dialysis, Department of Urology, Nara Medical University kn-affil= affil-num=12 en-affil=Organ Transplant Medicine, Tokyo Women’s Medical University kn-affil= affil-num=13 en-affil=Division of Urology, Department of Regenerative & Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=14 en-affil=Department of Kidney Transplantation Surgery, Tokyo Medical University Hachioji Medical Center kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba kn-affil= affil-num=17 en-affil=Department of Urology, Osaka University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Urology, Faculty of Medicine, Adrenal Surgery and Renal Transplantation, Kagawa University kn-affil= affil-num=19 en-affil=Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Urology, Toyama Prefectural Central Hospital kn-affil= affil-num=21 en-affil=Department of Nephrology, Toho University Faculty of Medicine kn-affil= affil-num=22 en-affil=Department of Kidney Transplant and Dialysis, Osaka City General Hospital kn-affil= affil-num=23 en-affil=Division of Renal Surgery and Transplantation, Department of Urology, Jichi Medical University kn-affil= affil-num=24 en-affil=Department of Blood Purification, Kagoshima University Hospital kn-affil= affil-num=25 en-affil=Department of Transplant Surgery, Japanese Red Cross Kumamoto Hospital kn-affil= affil-num=26 en-affil=Department of Urology, Chukyo Hospital, Japan Community Healthcare Organization kn-affil= affil-num=27 en-affil=Department of Renal Transplantation Surgery and Urology, Sapporo Hokuyu Hospital kn-affil= affil-num=28 en-affil=Department of Urology, Kanazawa University Hospital kn-affil= affil-num=29 en-affil=Department of Frontier Surgery, Chiba University School of Medicine kn-affil= affil-num=30 en-affil=Department of Urology, Ehime University kn-affil= affil-num=31 en-affil=Department of Urology, Sapporo Medical University kn-affil= affil-num=32 en-affil=Department of Transplant Surgery, Tokai University School of Medicine kn-affil= affil-num=33 en-affil=Department of Renal and Genitourinary Surgery, Faculty of Medicine, Hokkaido University kn-affil= affil-num=34 en-affil=Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University kn-affil= en-keyword=kidney transplantation kn-keyword=kidney transplantation en-keyword=donor-specific antibodies kn-keyword=donor-specific antibodies en-keyword=kidney exchange program kn-keyword=kidney exchange program en-keyword=virtual cross-matching kn-keyword=virtual cross-matching END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=6 article-no= start-page=836 end-page=849 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251028 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=C1orf50 Accelerates Epithelial-Mesenchymal Transition and the Cell Cycle of Hepatocellular Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with limited treatment options and a poor prognosis in advanced stages. To identify novel biomarkers and therapeutic targets, we investigated the role of chromosome 1 open reading frame 50 (C1orf50), a gene with a previously uncharacterized function in HCC.
Materials and Methods: We performed a comprehensive transcriptome data analysis of the human hepatocellular carcinoma project from The Cancer Genome Atlas (TCGA) and subsequently validated the oncogenic roles of C1orf50 using HCC cell lines.
Results: Using transcriptomic and clinical data from TCGA, we stratified 355 primary HCC samples based on C1orf50 expression levels. Patients with high C1orf50 expression exhibited significantly shorter overall survival, suggesting its association with aggressive tumor behavior. Differential expression and enrichment analyses revealed that C1orf50-high tumors were enriched in oncogenic pathways, including epithelial-mesenchymal transition (EMT), cell cycle activation, and stemness-related properties. Transcriptional regulatory network analysis detected 456 significantly dysregulated regulons, including ZEB1/2 and E2F2, key drivers of EMT and cell cycle, in the C1orf50-high group. In addition, we observed increased YAP1/TAZ signaling, further linking C1orf50 to stemness and therapeutic resistance. Functional data from CRISPR-based dependency screening suggested that several transcription factors up-regulated in the C1orf50-high state, such as ZBTB11 and CTCE, are essential for the survival of HCC cells. These findings indicate potential therapeutic vulnerabilities and support the rationale for targeting C1orf50-associated pathways.
Conclusion: C1orf50 is a novel biomarker of poor prognosis in HCC and a key regulator of oncogenic features such as EMT, cell cycle progression, and stemness. This study highlights the therapeutic potential of targeting C1orf50-related networks in aggressive subtypes of liver cancer. en-copyright= kn-copyright= en-aut-name=TANAKAATSUSHI en-aut-sei=TANAKA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OTANIYUSUKE en-aut-sei=OTANI en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MAEKAWAMASAKI en-aut-sei=MAEKAWA en-aut-mei=MASAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ROGACHEVSKAYAANNA en-aut-sei=ROGACHEVSKAYA en-aut-mei=ANNA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PEÑATIRSO en-aut-sei=PEÑA en-aut-mei=TIRSO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CHINVANESSA D. en-aut-sei=CHIN en-aut-mei=VANESSA D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TOYOOKASHINICHI en-aut-sei=TOYOOKA en-aut-mei=SHINICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ROEHRLMICHAEL H. en-aut-sei=ROEHRL en-aut-mei=MICHAEL H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FUJIMURAATSUSHI en-aut-sei=FUJIMURA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=6 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=9 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=stemness kn-keyword=stemness en-keyword=cell cycle kn-keyword=cell cycle en-keyword=epithelial‑mesenchymal transition kn-keyword=epithelial‑mesenchymal transition END start-ver=1.4 cd-journal=joma no-vol=478 cd-vols= no-issue= article-no= start-page=123708 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Two Japanese families with adult-onset leukoencephalopathy caused by pathogenic variants in CST3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=CST3 (NM_000099.4) encodes cystatin C, whose C-terminal truncating variants in this gene have recently been reported to cause adult-onset leukoencephalopathy, characterized by headaches, transient neurological symptoms, and distinct imaging findings. We present four patients from two Japanese families, including one with a novel variant (c.358-2_395del). Three patients from one family developed chronic headaches around the age of 20, whereas the patient from the other family remained asymptomatic until his fifties. mRNA analysis of the patient with c.358-2_395del revealed a splicing alteration leading to an in-frame deletion (p.Lys120_Gln133del), representing the first CST3 variant that does not result in a truncated protein. These findings broaden our understanding of the clinical and genetic spectra of CST3-related leukoencephalopathy (114 words). en-copyright= kn-copyright= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiomiKazutaka en-aut-sei=Shiomi en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoRyoji en-aut-sei=Goto en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuromiYumiko en-aut-sei=Kuromi en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsudaNozomu en-aut-sei=Matsuda en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanaiKazuaki en-aut-sei=Kanai en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurokawaRyo en-aut-sei=Kurokawa en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NomotoJunko en-aut-sei=Nomoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TanakaMasaki en-aut-sei=Tanaka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OmaeYosuke en-aut-sei=Omae en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KawaiYosuke en-aut-sei=Kawai en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TokunagaKatsushi en-aut-sei=Tokunaga en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=7 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=8 en-affil=Department of Neurology, Fukushima Medical University kn-affil= affil-num=9 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=12 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=13 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=14 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=15 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=16 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine kn-affil= affil-num=17 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=CST3 kn-keyword=CST3 en-keyword=Cystatin-C kn-keyword=Cystatin-C en-keyword=Leukodystrophy kn-keyword=Leukodystrophy en-keyword=Leukoencephalopathy kn-keyword=Leukoencephalopathy en-keyword=Middle cerebellar peduncle kn-keyword=Middle cerebellar peduncle en-keyword=MCP kn-keyword=MCP END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=189 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240827 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Post-spinel-type AB2O4 high-pressure phases in geochemistry and materials science en-subtitle= kn-subtitle= en-abstract= kn-abstract=Post-spinel-type AB2O4 compounds are stable at higher pressures than spinel phases. These compounds have garnered much interest in geo- and materials science for their geochemical importance as well as potential application as high ionic conductors and materials with strongly correlated electrons. Here, large-volume high-pressure syntheses, structural features and properties of post-spinels are reviewed. Prospects are discussed for future searches for post-spinel-type phases by applying advanced large-volume high-pressure technology. en-copyright= kn-copyright= en-aut-name=AkaogiMasaki en-aut-sei=Akaogi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiiTakayuki en-aut-sei=Ishii en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamauraKazunari en-aut-sei=Yamaura en-aut-mei=Kazunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Gakushuin University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Research Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=1869 cd-vols= no-issue=12 article-no= start-page=130860 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol–disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in Txn-F54L mutant rats; however, the details of why the Txn mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the Txn-F54L rats. en-copyright= kn-copyright= en-aut-name=BabaTakumi en-aut-sei=Baba en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UenoGo en-aut-sei=Ueno en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OheChika en-aut-sei=Ohe en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SajiShuku en-aut-sei=Saji en-aut-mei=Shuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoSachiko en-aut-sei=Yamamoto en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoMasaki en-aut-sei=Yamamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagawaHiroshi en-aut-sei=Nakagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkazakiNobuo en-aut-sei=Okazaki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Kawasaki-OhmoriIori en-aut-sei=Kawasaki-Ohmori en-aut-mei=Iori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakeshitaKohei en-aut-sei=Takeshita en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=2 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=3 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=4 en-affil=Structural Biology Division, Japan Synchrotron Radiation Research Institute kn-affil= affil-num=5 en-affil=Structural Biology Division, Japan Synchrotron Radiation Research Institute kn-affil= affil-num=6 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= affil-num=7 en-affil=Materials Sciences Research Center, Japan Atomic Energy Agency kn-affil= affil-num=8 en-affil=Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society (CROSS) kn-affil= affil-num=9 en-affil=Department of Molecular Oncology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University kn-affil= affil-num=11 en-affil=Life Science Research Infrastructure Group, Advanced Photon Technology Division, RIKEN SPring-8 Center kn-affil= en-keyword=Txn kn-keyword=Txn en-keyword=Thioredoxin kn-keyword=Thioredoxin en-keyword=Protein instability kn-keyword=Protein instability en-keyword=Thermosensitivity kn-keyword=Thermosensitivity en-keyword=Crystal structure kn-keyword=Crystal structure en-keyword=Molecular dynamics simulation kn-keyword=Molecular dynamics simulation END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=9 article-no= start-page=1135 end-page=1151 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Heart failure-specific cardiac fibroblasts contribute to cardiac dysfunction via the MYC–CXCL1–CXCR2 axis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heart failure (HF) is a growing global health issue. While most studies focus on cardiomyocytes, here we highlight the role of cardiac fibroblasts (CFs) in HF. Single-cell RNA sequencing of mouse hearts under pressure overload identified six CF subclusters, with one specific to the HF stage. This HF-specific CF population highly expresses the transcription factor Myc. Deleting Myc in CFs improves cardiac function without reducing fibrosis. MYC directly regulates the expression of the chemokine CXCL1, which is elevated in HF-specific CFs and downregulated in Myc-deficient CFs. The CXCL1 receptor, CXCR2, is expressed in cardiomyocytes, and blocking the CXCL1–CXCR2 axis mitigates HF. CXCL1 impairs contractility in neonatal rat and human iPSC-derived cardiomyocytes. Human CFs from failing hearts also express MYC and CXCL1, unlike those from controls. These findings reveal that HF-specific CFs contribute to HF via the MYC–CXCL1–CXCR2 pathway, offering a promising therapeutic target beyond cardiomyocytes. en-copyright= kn-copyright= en-aut-name=KomuroJin en-aut-sei=Komuro en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KatsukiToshiomi en-aut-sei=Katsuki en-aut-mei=Toshiomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KusumotoDai en-aut-sei=Kusumoto en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KoToshiyuki en-aut-sei=Ko en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoMasamichi en-aut-sei=Ito en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatagiriMikako en-aut-sei=Katagiri en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KubotaMasayuki en-aut-sei=Kubota en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaShintaro en-aut-sei=Yamada en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraTakahiro en-aut-sei=Nakamura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AkibaYohei en-aut-sei=Akiba en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KoukaThukaa en-aut-sei=Kouka en-aut-mei=Thukaa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KomuroKaoruko en-aut-sei=Komuro en-aut-mei=Kaoruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KimuraMai en-aut-sei=Kimura en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ItoShogo en-aut-sei=Ito en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=KomuroIssei en-aut-sei=Komuro en-aut-mei=Issei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 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=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=IedaMasaki en-aut-sei=Ieda en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 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 Frontier Cardiovascular Science, Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Frontier Cardiovascular Science, Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=12 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=13 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=16 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=18 en-affil=Department of Frontier Cardiovascular Science, Graduate 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, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of 50 krpm Ultra-High Speed IPMSM For EV Traction en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper develops an ultra-high-speed 50 krpm motor for traction applications. A typical IPMSM structure is used for the rotor in this paper. At ultra-high speeds, the winding structure has a large effect on winding losses. Hence, this paper investigates the AC loss of the winding. The AC loss includes the eddy current loss and circulating current loss in the winding. Additionally, the ultra-high speed raises concerns about the rotor's critical speed. Therefore, in this paper, the shaft of the developed motor is manufactured, and the critical speed is evaluated. en-copyright= kn-copyright= en-aut-name=TsunataRen en-aut-sei=Tsunata en-aut-mei=Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraMasaki en-aut-sei=Kimura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakemotoMasatsugu en-aut-sei=Takemoto en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImaiJun en-aut-sei=Imai en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Okayama University, Graduate School of Environmental, Life, Natural Science and Technology kn-affil= affil-num=2 en-affil=Okayama University, Graduate School of Environmental, Life, Natural Science and Technology kn-affil= affil-num=3 en-affil=Okayama University, Graduate School of Environmental, Life, Natural Science and Technology kn-affil= affil-num=4 en-affil=Okayama University, Graduate School of Environmental, Life, Natural Science and Technology kn-affil= en-keyword=IPMSM kn-keyword=IPMSM en-keyword=winding kn-keyword=winding en-keyword=traction motor kn-keyword=traction motor en-keyword=50 krpm kn-keyword=50 krpm en-keyword=eddy current loss kn-keyword=eddy current loss 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-κB-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-κB) 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-κB-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-κB-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=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=MoïsiJennifer C. en-aut-sei=Moïsi 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=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=38 cd-vols= no-issue=9 article-no= start-page=e70105 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=Ultrahigh‐Field MR‐Compatible Mechanical Tactile Stimulator for Investigating Somatosensory Processing in Small‐Bodied Animals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Common marmosets (Callithrix jacchus), small-bodied New World primates that share similar sensory processing pathways with human beings, have gained great interests. Their small body size allows imaging of brain activity with high spatial resolution and on a whole-brain scale using ultrahigh-field (UHF) magnetic resonance imaging (MRI) scanners. However, the strong magnetic field and the small size of the hand and forearm pose challenges in delivering tactile stimulation during fMRI experiments. In the present study, we developed an MR-compatible tactile dual-point stimulator to provide high-precision mechanical stimulation for exploring somatosensory processing in small-bodied animals. The study population consisted of a water phantom and three male common marmosets. Cerebral blood volume (CBV) weighted fMRI data were obtained with a gradient echo (GE), echo-planar imaging (EPI) sequence at 7T scanner. The output performance of the device was tested by a pressure sensor. The MR compatibility of the device was verified by measuring the temporal signal-to-noise ratio (tSNR) of a water phantom. To test the effectiveness of tactile stimulation, we conducted block designed tactile stimulation experiments on marmosets. A one-way repeated measures ANOVA was conducted for comparing the tSNR results. We performed one-sample t-tests to investigate the negative response of the forearm and hand stimulation with a threshold of t > 1.96 (p < 0.05). Performance tests revealed that mechanical stimulation (averaged force: 31.69 g) was applied with a delay of 12 ms. Phantom experiments confirmed that there was no significant difference in the tSNR among three (10 Hz, 1 Hz, and no-stimulus) conditions (F (2, 798) = 0.71, p = 0.49). The CBV activity results showed that the stimulator successfully elicited hand and forearm somatosensory activations in primary somatosensory areas. These results indicated that the device is well suited for small-bodied animal somatosensory studies. en-copyright= kn-copyright= en-aut-name=WangChenyu en-aut-sei=Wang en-aut-mei=Chenyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ImaiHirohiko en-aut-sei=Imai en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukunagaMasaki en-aut-sei=Fukunaga en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoHiroki en-aut-sei=Yamamoto en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YuYinghua en-aut-sei=Yu en-aut-mei=Yinghua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SekiKazuhiko en-aut-sei=Seki en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HanakawaTakashi en-aut-sei=Hanakawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmedaTatsuya en-aut-sei=Umeda en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YangJiajia en-aut-sei=Yang en-aut-mei=Jiajia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=Innovation Research Center for Quantum Medicine, Gifu University School of Medicine kn-affil= affil-num=3 en-affil=Section of Brain Function Information, National Institute for Physiological Sciences kn-affil= affil-num=4 en-affil=Graduate School of Human and Environmental Studies, Kyoto University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurophysiology, National Center of Neurology and Psychiatry kn-affil= affil-num=7 en-affil=Department of Integrated Neuroanatomy and Neuroimaging, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Integrated Neuroanatomy and Neuroimaging, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=primary somatosensory cortex kn-keyword=primary somatosensory cortex en-keyword=small-bodied animals kn-keyword=small-bodied animals en-keyword=tactile stimulation device kn-keyword=tactile stimulation device en-keyword=ultrahigh-field magnetic resonance imaging kn-keyword=ultrahigh-field magnetic resonance imaging 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, < 30 mmHg), suggesting normal pulmonary microcirculation. On the basis of these findings, pulmonary vasodilators were discontinued. Notably, a repeat exercise right heart catheterization demonstrated preserved pulmonary microcirculation, and the patient has remained asymptomatic for more than 2 years after discontinuing pulmonary-arterial-hypertension-targeted therapy.
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=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=599 cd-vols= no-issue=13 article-no= start-page=1914 end-page=1924 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250525 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characterization of molecular mechanisms of CaMKKα/1 oligomerization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is an activating kinase for calcium/calmodulin-dependent protein kinase type 1 (CaMKI), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), RAC-alpha serine/threonine-protein kinase (PKB), and AMP-activated protein kinase (AMPK) that has been reported to form an active oligomer in cells. Glutathione S-transferase (GST) pulldown assay from the extracts of COS-7 cells expressing GST- and His6-CaMKKα/1 mutants showed that the C-terminal region containing the autoinhibitory and calmodulin (CaM)-binding sequence (residues 438–463) is required for CaMKKα/1 homo-oligomerization. This was confirmed by the fact that the GST-CaMKKα/1 C-terminal domain (residues 435–505) directly interacted with EGFP-CaMKKα/1 residues 435–505 as well as with wild-type CaMKKα/1. Notably, once oligomerized in cells, CaMKKα/1 is neither exchangeable between the oligomeric complexes nor dissociated by Ca2+/CaM binding. These results support stable oligomerization of CaMKK in the cells by intermolecular self-association of its C-terminal region containing a regulatory domain. en-copyright= kn-copyright= en-aut-name=UenoyamaShun en-aut-sei=Uenoyama en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NittaHayato en-aut-sei=Nitta en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuizuFutoshi en-aut-sei=Suizu en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokumitsuHiroshi en-aut-sei=Tokumitsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=3 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Medical Technology, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=6 en-affil= kn-affil= en-keyword=calmodulin kn-keyword=calmodulin en-keyword=calmodulin-kinase cascade kn-keyword=calmodulin-kinase cascade en-keyword=CaMKKa/ kn-keyword=CaMKKa/ en-keyword=oligomerization kn-keyword=oligomerization en-keyword=protein–protein interaction kn-keyword=protein–protein interaction en-keyword=regulatory domain kn-keyword=regulatory domain END start-ver=1.4 cd-journal=joma no-vol=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’s 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=PEÑATIRSO en-aut-sei=PEÑA 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=4 cd-vols= no-issue=2 article-no= start-page=e70091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250427 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Olanzapine enabled rechallenge after lorlatinib-induced psychosis: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Lorlatinib is a third-generation tyrosine kinase inhibitor for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). While it has a high intracranial lesion control rate, it can also cause central nervous system complications, including psychotic symptoms. We present a case of lorlatinib-induced psychosis successfully managed with olanzapine, enabling lorlatinib rechallenge.
Case Presentation: A 32-year-old woman with ALK-positive NSCLC and brain metastases was started on lorlatinib. After 18 months, she developed hallucinations and delusions. Despite treatment with risperidone, her psychotic symptoms persisted, leading to hospitalization. Her symptoms resolved upon lorlatinib discontinuation while risperidone was continued. Given the critical role of lorlatinib in controlling brain metastases, rechallenge was considered. To mitigate concerns regarding drug interactions, risperidone was replaced with olanzapine. Following lorlatinib rechallenge with olanzapine, no recurrence of psychiatric symptoms was observed, allowing continued lorlatinib treatment. Additionally, no progression of lung cancer was noted.
Conclusion: Lorlatinib is an essential drug for controlling brain metastases in ALK-positive NSCLC. However, it can induce psychotic symptoms. When psychiatrists are involved in managing adverse effects during cancer treatment, close collaboration among oncologists, psychiatrists, and patients is essential. en-copyright= kn-copyright= en-aut-name=YokodeAkiyoshi en-aut-sei=Yokode en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraYuko en-aut-sei=Nakamura en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=psycho-oncology kn-keyword=psycho-oncology en-keyword=lorlatinib kn-keyword=lorlatinib en-keyword=lung cancer kn-keyword=lung cancer en-keyword=medication-induced psychosis kn-keyword=medication-induced psychosis END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=2 article-no= start-page=e70108 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250421 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case report of ineffective electroconvulsive therapy for chronic pain en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Somatic symptom disorder (SSD), which includes chronic pain, is a common mental disorder characterized by significant functional impairment and other psychiatric comorbidities. Electroconvulsive therapy (ECT) has been proposed as a potential treatment for refractory chronic pain. However, evidence supporting its efficacy is limited and/or low quality. We present a case of SSD with chronic pain in which ECT was ineffective.
Case Presentation: The patient was a 63-year-old man with chronic pain in the lower back, buttocks, thighs, and soles of the feet. The duration of his chronic pain was 3.8 years. He was diagnosed with Bertolotti's syndrome and SSD. He did not meet the criteria for major depressive disorder. He kept physically active by walking and doing exercises to distract himself from his pain. He strongly perceived pain as a physical issue and preferred ECT over psychotherapy. Despite undergoing 10 ECT sessions with adequate seizures, his pain persisted. After four sessions, he experienced despair over the lack of improvement in pain, which temporarily intensified his suicidal ideation. After undergoing ECT, he continued to maintain his activities, including walking and exercise, while his catastrophic thinking about pain persisted.
Conclusion: The ineffectiveness of ECT in this case highlights the need for balanced counseling, particularly for patients who consider ECT a last-resort treatment. Psychological monitoring and depression screening are essential, especially given the risk of heightened despair or suicidal ideation when ECT is ineffective. Therefore, collaborative decision-making based on accurate information is vital. en-copyright= kn-copyright= en-aut-name=FukaoTakashi en-aut-sei=Fukao en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsadaKazushi en-aut-sei=Asada en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=RiHirotoshi en-aut-sei=Ri en-aut-mei=Hirotoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=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 Hospital kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University 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=chronic pain kn-keyword=chronic pain en-keyword=electroconvulsive therapy kn-keyword=electroconvulsive therapy en-keyword=pain disorder kn-keyword=pain disorder en-keyword=somatic symptom disorder kn-keyword=somatic symptom disorder END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=12633 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of emergency intensive care unit occupancy due to brain-dead organ donors with ambulance diversion en-subtitle= kn-subtitle= en-abstract= kn-abstract=Our study aims to explore how intensive care unit (ICU) occupancy by brain-dead organ donors affects emergency ambulance diversions. In this retrospective, single-center study at an emergency ICU (EICU), brain-dead organ donors were managed until organ procurement. We classified each day between August 1, 2021, and July 31, 2023, as either an exposure day (any day with a brain-dead organ donor in the EICU from admission to organ procurement) or a control day (all other days). The study compared these days and used multiple logistic regression analysis to assess the impact of EICU occupancy by brain-dead organ donors on ambulance diversions. Over two years, 6,058 emergency patients were transported by ambulance, with 1327 admitted to the EICU, including 13 brain-dead organ donors. Brain-dead donors had longer EICU stays (17 vs. 2 days, P < 0.001). With 168 exposure and 562 control days, EICU occupancy was higher on exposure days (75% vs. 67%, P = 0.003), leading to more ambulance diversions. Logistic regression showed exposure days significantly increased ambulance diversions, with an odds ratio of 1.79 (95% CIs 1.10-2.88). This study shows that managing brain-dead organ donors in the EICU leads to longer stays and higher occupancy, resulting in more frequent ambulance diversions. These findings highlight the critical need for policies that optimize ICU resource allocation while maintaining the infrastructure necessary to support organ donation programs and ensuring continued care for brain-dead donors, who play an essential role in addressing the organ shortage crisis. en-copyright= kn-copyright= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HisamuraMasaki en-aut-sei=Hisamura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Ambulance diversion kn-keyword=Ambulance diversion en-keyword=Bed occupancy kn-keyword=Bed occupancy en-keyword=Brain death kn-keyword=Brain death en-keyword=Emergency medical services kn-keyword=Emergency medical services en-keyword=Intensive care units kn-keyword=Intensive care units en-keyword=Organ donation kn-keyword=Organ donation END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue= article-no= start-page=39 end-page=45 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Practicing the Innovation Loop: 2024 Report on Advanced Hospital Practicums and Future Challenges kn-title=イノベーションループの実践：2024年度先進病院実習報告と未来課題 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HARADANahoko en-aut-sei=HARADA en-aut-mei=Nahoko kn-aut-name=原田奈穂子 kn-aut-sei=原田 kn-aut-mei=奈穂子 aut-affil-num=1 ORCID= en-aut-name=TAKAHASHISatoshi en-aut-sei=TAKAHASHI en-aut-mei=Satoshi kn-aut-name=髙橋智 kn-aut-sei=髙橋 kn-aut-mei=智 aut-affil-num=2 ORCID= en-aut-name=MORITomoaki en-aut-sei=MORI en-aut-mei=Tomoaki kn-aut-name=森友明 kn-aut-sei=森 kn-aut-mei=友明 aut-affil-num=3 ORCID= en-aut-name=HIKASAHaruka en-aut-sei=HIKASA en-aut-mei=Haruka kn-aut-name=日笠晴香 kn-aut-sei=日笠 kn-aut-mei=晴香 aut-affil-num=4 ORCID= en-aut-name=SHISHIDOKeisuke en-aut-sei=SHISHIDO en-aut-mei=Keisuke kn-aut-name=宍戸圭介 kn-aut-sei=宍戸 kn-aut-mei=圭介 aut-affil-num=5 ORCID= en-aut-name=MAGARIMasaki en-aut-sei=MAGARI en-aut-mei=Masaki kn-aut-name=曲正樹 kn-aut-sei=曲 kn-aut-mei=正樹 aut-affil-num=6 ORCID= en-aut-name=WATANABEToyohiko en-aut-sei=WATANABE en-aut-mei=Toyohiko kn-aut-name=渡邉豊彦 kn-aut-sei=渡邉 kn-aut-mei=豊彦 aut-affil-num=7 ORCID= en-aut-name=WangJin en-aut-sei=Wang en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MORITAMizuki en-aut-sei=MORITA en-aut-mei=Mizuki kn-aut-name=森田瑞樹 kn-aut-sei=森田 kn-aut-mei=瑞樹 aut-affil-num=9 ORCID= affil-num=1 en-affil=Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=2 en-affil=Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=3 en-affil=Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=4 en-affil=Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=5 en-affil=Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=6 en-affil=Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=7 en-affil=Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=8 en-affil=Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 affil-num=9 en-affil=Academic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域 END start-ver=1.4 cd-journal=joma no-vol=301 cd-vols= no-issue=4 article-no= start-page=108334 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of basic amino acid residues in substrate binding and transport of the light-driven anion pump Synechocystis halorhodopsin (SyHR) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Microbial rhodopsins are photoreceptive seventransmembrane a-helical proteins, many of which function as ion transporters, primarily for small monovalent ions such as Na+, K+, Cl-, Br-, and I-. Synechocystis halorhodopsin (SyHR), identified from the cyanobacterium Synechocystis sp. PCC 7509, uniquely transports the polyatomic divalent SO42- inward, in addition to monovalent anions (Cl- and Br-). In this study, we conducted alanine-scanning mutagenesis on twelve basic amino acid residues to investigate the anion transport mechanism of SyHR. We quantitatively evaluated the Cl-and SO42- transport activities of the WT SyHR and its mutants. The results showed a strong correlation between the Cl-and SO42- transport activities among them (R = 0.94), suggesting a shared pathway for both anions. Notably, the R71A mutation selectively abolished SO42- transport activity while maintaining Cl- transport, whereas the H167A mutation significantly impaired both Cl-and SO42- transport. Furthermore, spectroscopic analysis revealed that the R71A mutant lost its ability to bind SO42- due to the absence of a positive charge, while the H167A mutant failed to accumulate the O intermediate during the photoreaction cycle (photocycle) due to reduced hydrophilicity. Additionally, computational analysis revealed the SO42- binding modes and clarified the roles of residues involved in its binding around the retinal chromophore. Based on these findings and previous structural information, we propose that the positive charge and hydrophilicity of Arg71 and His167 are crucial for the formation of the characteristic initial and transient anion-binding site of SyHR, enabling its unique ability to bind and transport both Cl-and SO42-. en-copyright= kn-copyright= en-aut-name=NakamaMasaki en-aut-sei=Nakama en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NojiTomoyasu en-aut-sei=Noji en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshizawaSusumu en-aut-sei=Yoshizawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshikitaHiroshi en-aut-sei=Ishikita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=microbial rhodopsin kn-keyword=microbial rhodopsin en-keyword=anion transport kn-keyword=anion transport en-keyword=retinal kn-keyword=retinal en-keyword=membrane protein kn-keyword=membrane protein en-keyword=photobiology kn-keyword=photobiology END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue= article-no= start-page=121 end-page=132 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=CASE STUDY：In-house lawyer kn-title=企業法務に携わる法律家に求められているものは何か en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SatoMasaki en-aut-sei=Sato en-aut-mei=Masaki kn-aut-name=佐藤雅樹 kn-aut-sei=佐藤 kn-aut-mei=雅樹 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=パーク２４株式会社 END start-ver=1.4 cd-journal=joma no-vol=85 cd-vols= no-issue=6 article-no= start-page=1082 end-page=1096 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250314 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Brain metastasis is a poor prognostic factor in patients with cancer. Despite showing efficacy in many extracranial tumors, immunotherapy with anti–PD-1 mAb or anti–CTLA4 mAb seems to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti–PD-1 and anti–CTLA4 mAbs has a potent antitumor effect on brain metastasis, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. In this study, we analyzed the tumor-infiltrating lymphocytes in murine models of brain metastasis that responded to anti–CTLA4 and anti–PD-1 mAbs. Activated CD4+ T follicular helper (TFH) cells with high CTLA4 expression characteristically infiltrated the intracranial TME, which were activated by combination anti–CTLA4 and anti–PD-1 treatment. The loss of TFH cells suppressed the additive effect of CTLA4 blockade on anti–PD-1 mAb. B-cell–activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo proinflammatory M1-like macrophages, in the intracranial TME induced B-cell and TFH-cell infiltration and activation. Furthermore, the intracranial TME of patients with non–small cell lung cancer featured TFH- and B-cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell cross-talk in the intracranial TME that facilitates an additive antitumor effect of CTLA4 blockade with anti–PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for brain metastases.
Significance: B-cell and CD4+ T follicular helper cell activation via BAFF/APRIL from abundant myeloid cells in the intracranial tumor microenvironment enables a combinatorial effect of CTLA4 and PD-1 blockade in brain metastases. en-copyright= kn-copyright= en-aut-name=NinomiyaToshifumi en-aut-sei=Ninomiya en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KemmotsuNaoya en-aut-sei=Kemmotsu en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MukoharaFumiaki en-aut-sei=Mukohara en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyamotoAi en-aut-sei=Miyamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OkamotoIsamu en-aut-sei=Okamoto en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Medical Protein Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=18 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=e70077 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case of invasive pulmonary aspergillosis associated with clozapine-induced agranulocytosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Clozapine-induced agranulocytosis (CLIA) is a rare but serious complication. Fever associated with CLIA is typically treated with broad-spectrum antimicrobials, but empiric antifungal therapy is rarely used. While bacterial and viral infections have been reported in CLIA cases, no cases of fungal infections complicated by CLIA have been documented. We report the first case of CLIA complicated by invasive pulmonary aspergillosis (IPA) in a patient with schizophrenia. The diagnosis of IPA was made using serum beta-D-glucan, Aspergillus galactomannan antigen tests, and chest computed tomography (CT).
Case presentation: We present a case of a 51-year-old man with schizophrenia who developed CLIA complicated by IPA. The patient, diagnosed with treatment-resistant schizophrenia, was started on clozapine, but 9 months later he presented with fever, cough, leukopenia, and neutropenia. Clozapine was discontinued, and empirical treatments with cefepime and filgrastim were initiated. Serum beta-D-glucan and Aspergillus galactomannan antigen tests were positive, and chest CT showed well-circumscribed nodules, leading to a probable diagnosis of IPA. Antifungal therapy was switched from micafungin to voriconazole according to guidelines. His neutropenia and fever improved, and he was re-transferred to a psychiatric hospital.
Conclusion: CLIA can be complicated by fungal infections. When patients with CLIA present with fever, fungal infections, including IPA, should be considered in the differential diagnosis. Serological tests, including beta-D-glucan and Aspergillus galactomannan, are useful for the diagnosis of IPA as well as the appropriate use of antifungal agents in patients with CLIA. en-copyright= kn-copyright= en-aut-name=YokodeAkiyoshi en-aut-sei=Yokode en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoRyota en-aut-sei=Sato en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MishimaMomoko en-aut-sei=Mishima en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YadaYuji en-aut-sei=Yada en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=7 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=8 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=9 en-affil=Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences kn-affil= affil-num=10 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=clozapine-induced agranulocytosis kn-keyword=clozapine-induced agranulocytosis en-keyword=fungal infections kn-keyword=fungal infections en-keyword=invasive pulmonary aspergillosis kn-keyword=invasive pulmonary aspergillosis en-keyword=schizophrenia kn-keyword=schizophrenia END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=e70062 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trends in uptake of cancer screening among people with severe mental illness before and after the COVID-19 pandemic in Japan: A repeated cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: The aim of this study was to investigate trends in cancer screening participation among people with severe mental illness (PSMI) from periods before and after the COVID-19 pandemic.
Methods: In this repeated cross-sectional study, we used anonymized datasets on municipal cancer screening participation among PSMI in Okayama City. The data covered fiscal year (FY) 2018 to FY2022; we used the municipal cancer screening database and Medical Payment for Services and Supports for Persons with Disabilities. PSMI were defined as those with schizophrenia or related psychotic disorders (F20-29) or bipolar disorder (F30 or F31), identified using International Classification of Diseases, Tenth Revision, codes. The analysis included men and women aged 40-69 years for colorectal and lung cancer screening; men and women aged 50-69 years for gastric cancer screening; women aged 40-69 years for breast cancer screening; and women aged 20-69 years for cervical cancer screening. Municipal cancer screening rates among PSMI were calculated for each FY.
Results: For all cancer types, cancer screening rates for PSMI in FY2020 (colorectal: 9.0%; lung: 11.6%; gastric: 4.9%; breast: 6.2%; and cervical: 6.1%) were lower than the rates in FY2019 (11.5%, 14.0%, 6.5%, 9.3%, and 8.3%, respectively). In FY2022, the rates (9.9%, 12.9%; 5.3%; 8.0%, and 6.9%, respectively) recovered, but remained low.
Conclusion: This study showed that cancer screening rates among PSMI were very low, both before and after the COVID-19 pandemic. Efforts to encourage participation in cancer screening in this population are urgently needed. en-copyright= kn-copyright= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayaNaoki en-aut-sei=Nakaya en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukiKoji en-aut-sei=Otsuki en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimazuTaichi en-aut-sei=Shimazu en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimoriMaiko en-aut-sei=Fujimori en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HinotsuShiro en-aut-sei=Hinotsu en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagoshiKiwamu en-aut-sei=Nagoshi en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchitomiYosuke en-aut-sei=Uchitomi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InagakiMasatoshi en-aut-sei=Inagaki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=4 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= affil-num=5 en-affil=Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=6 en-affil=Division of Survivorship Research, National Cancer Center Institute for Cancer Control, National Cancer Center kn-affil= affil-num=7 en-affil=Department of Biostatistics and Data Management, Sapporo Medical University kn-affil= affil-num=8 en-affil=Department of Environmental Medicine and Public Health, Faculty of Medicine, Shimane University kn-affil= affil-num=9 en-affil=Department of Cancer Survivorship and Digital Medicine, The Jikei University School of Medicine kn-affil= affil-num=10 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= en-keyword=bipolar disorder kn-keyword=bipolar disorder en-keyword=cancer screening kn-keyword=cancer screening en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=healthcare disparities kn-keyword=healthcare disparities en-keyword=schizophrenia kn-keyword=schizophrenia END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimization of workflow processes for sustainable paternal involvement: case study of an academic “daddy surgeon” in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Work–life balance is often discussed in Japan. Yet surgeons find it challenging to take paternity leave because of their demanding surgical duties and a strong sense of responsibility. One Japanese male surgeon had his first paternity experience as a research fellow in the US. When he returned to Japan, he resumed his surgical training and started a research project to become an academic surgeon. When he and his wife were expecting their second child, they discussed his paternity participation before the delivery and decided on a sustainable paternity participation plan. By coordinating his responsibilities with his co-workers, he limited his attendance at work to daytime hours only for 1 month to manage paternity duties. This adjustment did not affect the number of main and assistant operations conducted that month and effective optimization of workflow processes decreased the extra workload for other team members. His experience suggests that the optimization of workflow processes can enhance personal life, including paternity participation. (150/150). 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=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=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=TakeharaYuko en-aut-sei=Takehara en-aut-mei=Yuko 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=MinagiHitoshi en-aut-sei=Minagi en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakamotoMasaki en-aut-sei=Sakamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=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=KataokaHitomi en-aut-sei=Kataoka en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Surgery, Okayama Saiseikai General Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Integrated Clinical Education Center, Kyoto University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Optimization of workflow processes kn-keyword=Optimization of workflow processes en-keyword=Sustainable paternity participation kn-keyword=Sustainable paternity participation en-keyword=“Daddy surgeon” kn-keyword=“Daddy surgeon” END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=2 article-no= start-page=292 end-page=305 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=The role of C1orf50 in breast cancer progression and prognosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although the prognosis of breast cancer has significantly improved compared to other types of cancer, there are still some patients who expire due to recurrence or metastasis. Therefore, it is necessary to develop a method to identify patients with poor prognosis at the early stages of cancer. In the process of discovering new prognostic markers from genes of unknown function, we found that the expression of C1orf50 determines the prognosis of breast cancer patients, especially for those with Luminal A breast cancer. This study aims to elucidate the molecular role of C1orf50 in breast cancer progression. Bioinformatic analyses of the breast cancer dataset of TCGA, and in vitro analyses, reveal the molecular pathways influenced by C1orf50 expression. C1orf50 knockdown suppressed the cell cycle of breast cancer cells and weakened their ability to maintain the undifferentiated state and self-renewal capacity. Interestingly, upregulation of C1orf50 increased sensitivity to CDK4/6 inhibition. In addition, C1orf50 was found to be more abundant in breast cancer cells than in normal breast epithelium, suggesting C1orf50’s involvement in breast cancer pathogenesis. Furthermore, the mRNA expression level of C1orf50 was positively correlated with the expression of PD-L1 and its related factors. These results suggest that C1orf50 promotes breast cancer progression through cell cycle upregulation, maintenance of cancer stemness, and immune evasion mechanisms. Our study uncovers the biological functions of C1orf50 in Luminal breast cancer progression, a finding not previously reported in any type of cancer. 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=TanakaAtsushi en-aut-sei=Tanaka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaekawaMasaki en-aut-sei=Maekawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PeñaTirso en-aut-sei=Peña en-aut-mei=Tirso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 ORCID= en-aut-name=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=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= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=13 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=14 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=Luminal A breast cancer kn-keyword=Luminal A breast cancer en-keyword=Cell cycle kn-keyword=Cell cycle en-keyword=Immune evasion kn-keyword=Immune evasion en-keyword=YAP/TAZ kn-keyword=YAP/TAZ END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=24716 end-page= 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=A nationwide longitudinal survey of infantile injury and its recurrence in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Injury recurrence in young children is a significant public health concern, as it may indicate an unfavorable home environment. This study evaluates whether infantile injuries increase recurrence during preschool years, contributing to more effective prevention strategies for vulnerable families. The study included 20,191 children from "The Longitudinal Survey of Babies in the 21st Century," a representative sample of infants born in Japan between May 10 and 24, 2010. We conducted a logistic regression analysis to compare injury recurrence risk between children aged 18 months to seven years with and without infantile injury histories. The study revealed that infants with a history of injuries had a higher risk of subsequent hospital visits for injuries during preschool years (crude Odds Ratio (cOR) 1.52, 95% CI, 1.41-1.64, adjusted OR (aOR) 1.48, 95% CI 1.37-1.60). Specific injuries, such as falls (aOR 1.34, 95% CI, 1.26-1.43), pinches (aOR 1.22, 95% CI, 1.15-1.29), drowning (aOR 1.29, 95% CI, 1.19-1.40), ingestion (aOR 1.35, 95% CI, 1.17-1.55), and burns (aOR 1.47, 95% CI, 1.31-1.65), independently increased the risk of future injuries. Our findings highlight the necessity of universal safety measures in the home environment and targeted interventions for families with a history of high-risk injuries. en-copyright= kn-copyright= en-aut-name=HiraokaTomohiro en-aut-sei=Hiraoka en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HisamuraMasaki en-aut-sei=Hisamura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Retrospective cohort study kn-keyword=Retrospective cohort study en-keyword=Injury recurrence kn-keyword=Injury recurrence en-keyword=Injury prevention kn-keyword=Injury prevention END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=1 article-no= start-page=1 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240730 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Potential dopaminergic deficit in patients with geriatric psychiatric disorders as revealed by DAT-SPECT: a cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background It has been reported that patients with geriatric psychiatric disorders include many cases of the prodromal stages of neurodegenerative diseases. Abnormal I-123-2 beta-carbomethoxy-3 beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane dopamine transporter single-photon emission computed tomography (DAT-SPECT) reveals a nigrostriatal dopaminergic deficit and is considered useful to detect dementia with Lewy bodies and Parkinson's disease as well as progressive supranuclear palsy and corticobasal degeneration. We aimed to determine the proportion of cases that are abnormal on DAT-SPECT in patients with geriatric psychiatric disorders and to identify their clinical profile.
Methods The design is a cross-sectional study. Clinical findings of 61 inpatients aged 60 years or older who underwent DAT-SPECT and had been diagnosed with psychiatric disorders, but not neurodegenerative disease or dementia were analysed.
Results 36 of 61 (59%) had abnormal results on DAT-SPECT. 54 of 61 patients who had DAT-SPECT (89%) had undergone I-123-metaiodobenzylguanidine myocardial scintigraphy (I-123-MIBG scintigraphy); 12 of the 54 patients (22.2%) had abnormal findings on I-123-MIBG scintigraphy. There were no cases that were normal on DAT-SPECT and abnormal on I-123-MIBG scintigraphy. DAT-SPECT abnormalities were more frequent in patients with late-onset (55 years and older) psychiatric disorders (69.0%) and depressive disorder (75.7%), especially late-onset depressive disorder (79.3%).
Conclusion Patients with geriatric psychiatric disorders include many cases showing abnormalities on DAT-SPECT. It is suggested that these cases are at high risk of developing neurodegenerative diseases characterised by a dopaminergic deficit. It is possible that patients with geriatric psychiatric disorders with abnormal findings on DAT-SPECT tend to show abnormalities on DAT-SPECT first rather than on I-123-MIBG scintigraphy. en-copyright= kn-copyright= en-aut-name=TakenoshitaShintaro en-aut-sei=Takenoshita en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=NishikawaNaoto en-aut-sei=Nishikawa en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MikiTomoko en-aut-sei=Miki en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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 Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Hospital 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 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= END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue=3 article-no= start-page=e70003 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240822 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Forgetfulness in adult attention-deficit/hyperactivity disorder masks transient epileptic amnesia: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Inattention due to attention-deficit/hyperactivity disorder (ADHD) can lead to forgetfulness. Transient epileptic amnesia (TEA) can cause forgetfulness, similar to ADHD. We report a patient with ADHD who developed TEA.
Case Presentation: The patient was a 40-year-old woman with ADHD. She has been prone to forgetfulness since childhood. Two years before visiting our outpatient clinic, she had begun to occasionally forget events that had occurred several days earlier. However, she was largely unaware of the emergence of new amnestic symptoms. She had also begun to experience various other amnestic symptoms 2 months before she visited our clinic, which prompted her to visit our outpatient clinic. The combination of a detailed interview, electroencephalography (EEG) examination, and consideration of TEA enabled us to diagnose her with TEA and provide treatment accordingly. In our patient, daily forgetfulness due to ADHD delayed the recognition of new additional forgetfulness attributed to TEA.
Conclusion: Psychiatrists need to consider TEA when patients with ADHD present with changes in or exacerbation of forgetfulness. We report a patient with ADHD who developed TEA. In our patient, daily forgetfulness due to ADHD delayed the recognition of new additional forgetfulness attributed to TEA. Psychiatrists need to consider TEA when patients with ADHD present with changes or exacerbation of forgetfulness. en-copyright= kn-copyright= en-aut-name=FukaoTakashi en-aut-sei=Fukao en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, OkayamaUniversity Hospital kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, OkayamaUniversity Hospital kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, OkayamaUniversity Hospital kn-affil= affil-num=4 en-affil=Department of Neuropsychiatry, OkayamaUniversity Hospital kn-affil= affil-num=5 en-affil=Okayama University Hospital Gender Center kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, OkayamaUniversity Faculty of Medicine, Dentistry andPharmaceutical Sciences kn-affil= en-keyword=anti-seizure medications kn-keyword=anti-seizure medications en-keyword=attention-deficit/hyperactivity disorder kn-keyword=attention-deficit/hyperactivity disorder en-keyword=electroencephalography kn-keyword=electroencephalography en-keyword=transient epileptic amnesia kn-keyword=transient epileptic amnesia END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=4600 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Photoinduced dynamics during electronic transfer from narrow to wide bandgap layers in one-dimensional heterostructured materials en-subtitle= kn-subtitle= en-abstract= kn-abstract=Electron transfer is a fundamental energy conversion process widely present in synthetic, industrial, and natural systems. Understanding the electron transfer process is important to exploit the uniqueness of the low-dimensional van der Waals (vdW) heterostructures because interlayer electron transfer produces the function of this class of material. Here, we show the occurrence of an electron transfer process in one-dimensional layer-stacking of carbon nanotubes (CNTs) and boron nitride nanotubes (BNNTs). This observation makes use of femtosecond broadband optical spectroscopy, ultrafast time-resolved electron diffraction, and first-principles theoretical calculations. These results reveal that near-ultraviolet photoexcitation induces an electron transfer from the conduction bands of CNT to BNNT layers via electronic decay channels. This physical process subsequently generates radial phonons in the one-dimensional vdW heterostructure material. The gathered insights unveil the fundamentals physics of interfacial interactions in low dimensional vdW heterostructures and their photoinduced dynamics, pushing their limits for photoactive multifunctional applications. en-copyright= kn-copyright= en-aut-name=SaidaYuri en-aut-sei=Saida en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GauthierThomas en-aut-sei=Gauthier en-aut-mei=Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuzukiHiroo en-aut-sei=Suzuki en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhmuraSatoshi en-aut-sei=Ohmura en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShikataRyo en-aut-sei=Shikata en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwasakiYui en-aut-sei=Iwasaki en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NoyamaGodai en-aut-sei=Noyama en-aut-mei=Godai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KishibuchiMisaki en-aut-sei=Kishibuchi en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaYuichiro en-aut-sei=Tanaka en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YajimaWataru en-aut-sei=Yajima en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=GodinNicolas en-aut-sei=Godin en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=PrivaultGael en-aut-sei=Privault en-aut-mei=Gael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TokunagaTomoharu en-aut-sei=Tokunaga en-aut-mei=Tomoharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OnoShota en-aut-sei=Ono en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KoshiharaShin-Ya en-aut-sei=Koshihara en-aut-mei=Shin-Ya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TsurutaKenji en-aut-sei=Tsuruta en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HayashiYasuhiko en-aut-sei=Hayashi en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=BertoniRoman en-aut-sei=Bertoni en-aut-mei=Roman kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HadaMasaki en-aut-sei=Hada en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Graduate School of Science and Technology, University of Tsukuba kn-affil= affil-num=2 en-affil=Univ Rennes, CNRS, IPR (Institut de Physique de Rennes) UMR 6251 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=Faculty of Engineering, Hiroshima Institute of Technology kn-affil= affil-num=5 en-affil=Graduate School of Science and Technology, University of Tsukuba kn-affil= affil-num=6 en-affil=Graduate School of Science and Technology, University of Tsukuba kn-affil= affil-num=7 en-affil=Graduate School of Science and Technology, University of Tsukuba kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Science and Technology, University of Tsukuba kn-affil= affil-num=11 en-affil=Univ Rennes, CNRS, IPR (Institut de Physique de Rennes) UMR 6251 kn-affil= affil-num=12 en-affil=Univ Rennes, CNRS, IPR (Institut de Physique de Rennes) UMR 6251 kn-affil= affil-num=13 en-affil=Graduate School of Engineering, Nagoya University kn-affil= affil-num=14 en-affil=Institute for Materials Research, Tohoku University kn-affil= affil-num=15 en-affil=School of Science, Tokyo Institute of Technology kn-affil= affil-num=16 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=17 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=18 en-affil=Univ Rennes, CNRS, IPR (Institut de Physique de Rennes) UMR 6251 kn-affil= affil-num=19 en-affil=Institute of Pure and Applied Science and Tsukuba Research Center for Energy Materials Science (TREMS), University of Tsukuba kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=19 article-no= start-page=21287 end-page=21297 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Superstructure of Fe5–xGeTe2 Determined by Te K-Edge Extended X-ray Absorption Fine Structure and Te Kα X-ray Fluorescence Holography en-subtitle= kn-subtitle= en-abstract= kn-abstract=The local structure of the two-dimensional van der Waals material, Fe5–xGeTe2, which exhibits unique structural/magnetic phase transitions, was investigated by Te K-edge extended X-ray absorption fine structure (EXAFS) and Te Kα X-ray fluorescence holography (XFH) over a wide temperature range. The formation of a trimer of Te atoms at low temperatures has been fully explored using these methods. An increase in the Te–Fe distance at approximately 150 K was suggested by EXAFS and presumably indicates the formation of a Te trimer. Moreover, XFH displayed clear atomic images of Te atoms. Additionally, the distance between the Te atoms shortened, as confirmed from the atomic images reconstructed from XFH, indicating the formation of a trimer of Te atoms, i.e., a charge-ordered (3⎯⎯√×3⎯⎯√)𝑅30◦ superstructure. Furthermore, Te Kα XFH provided unambiguous atomic images of Fe atoms occupying the Fe1 site; the images were not clearly observed in the Ge Kα XFH that was previously reported because of the low occupancy of Fe and Ge atoms. In this study, EXAFS and XFH clearly showed the local structure around the Te atom; in particular, the formation of Te trimers caused by charge-ordered phase transitions was clearly confirmed. The charge-ordered phase transition is fully discussed based on the structural variation at low temperatures, as established from EXAFS and XFH. en-copyright= kn-copyright= en-aut-name=EguchiRitsuko en-aut-sei=Eguchi en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SekharHalubai en-aut-sei=Sekhar en-aut-mei=Halubai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraKoji en-aut-sei=Kimura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasaiHirokazu en-aut-sei=Masai en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HappoNaohisa en-aut-sei=Happo en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkedaMitsuki en-aut-sei=Ikeda en-aut-mei=Mitsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoYuki en-aut-sei=Yamamoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UtsumiMasaki en-aut-sei=Utsumi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GotoHidenori en-aut-sei=Goto en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakabayashiYasuhiro en-aut-sei=Takabayashi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TajiriHiroo en-aut-sei=Tajiri en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayashiKoichi en-aut-sei=Hayashi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KubozonoYoshihiro en-aut-sei=Kubozono en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Physical Science and Technology, Nagoya Institute of Technology kn-affil= affil-num=3 en-affil=Department of Physical Science and Technology, Nagoya Institute of Technology kn-affil= affil-num=4 en-affil=Department of Materials and Chemistry, National Institute of Advanced Industrial Science and Technology (AIST) kn-affil= affil-num=5 en-affil=Graduate School of Information Sciences, Hiroshima City University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=10 en-affil=Department of Physical Science and Technology, Nagoya Institute of Technology kn-affil= affil-num=11 en-affil=Japan Synchrotron Radiation Research Institute (JASRI) kn-affil= affil-num=12 en-affil=Department of Physical Science and Technology, Nagoya Institute of Technology kn-affil= affil-num=13 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=6723 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240320 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of a novel AAK1 inhibitor via Kinobeads-based screening en-subtitle= kn-subtitle= en-abstract= kn-abstract=A chemical proteomics approach using Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor-immobilized sepharose (TIM-063-Kinobeads) identified main targets such as CaMKK alpha/1 and beta/2, and potential off-target kinases, including AP2-associated protein kinase 1 (AAK1), as TIM-063 interactants. Because TIM-063 interacted with the AAK1 catalytic domain and inhibited its enzymatic activity moderately (IC50 = 8.51 mu M), we attempted to identify potential AAK1 inhibitors from TIM-063-derivatives and found a novel AAK1 inhibitor, TIM-098a (11-amino-2-hydroxy-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) which is more potent (IC50 = 0.24 mu M) than TIM-063 without any inhibitory activity against CaMKK isoforms and a relative AAK1-selectivity among the Numb-associated kinases family. TIM-098a could inhibit AAK1 activity in transfected cultured cells (IC50 = 0.87 mu M), indicating cell-membrane permeability of the compound. Overexpression of AAK1 in HeLa cells significantly reduced the number of early endosomes, which was blocked by treatment with 10 mu M TIM-098a. These results indicate TIM-063-Kinobeads-based chemical proteomics is efficient for identifying off-target kinases and re-evaluating the kinase inhibitor (TIM-063), leading to the successful development of a novel inhibitory compound (TIM-098a) for AAK1, which could be a molecular probe for AAK1. TIM-098a may be a promising lead compound for a more potent, selective and therapeutically useful AAK1 inhibitor. en-copyright= kn-copyright= en-aut-name=YoshidaAkari en-aut-sei=Yoshida en-aut-mei=Akari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoFumiya en-aut-sei=Matsumoto en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyagawaTomoyuki en-aut-sei=Miyagawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkinoRei en-aut-sei=Okino en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkedaYumeya en-aut-sei=Ikeda en-aut-mei=Yumeya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TadaNatsume en-aut-sei=Tada en-aut-mei=Natsume kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GotohAkira en-aut-sei=Gotoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HatanoNaoya en-aut-sei=Hatano en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MorishitaRyo en-aut-sei=Morishita en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SunatsukiYukinari en-aut-sei=Sunatsuki en-aut-mei=Yukinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NilssonUlf J. en-aut-sei=Nilsson en-aut-mei=Ulf J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshikawaTeruhiko en-aut-sei=Ishikawa en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TokumitsuHiroshi en-aut-sei=Tokumitsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=4 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=5 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=6 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=11 en-affil=CellFree Sciences Co. Ltd kn-affil= affil-num=12 en-affil=Organelle Systems Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=13 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=14 en-affil=Department of Chemistry, Lund University kn-affil= affil-num=15 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=16 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=1 article-no= start-page=63 end-page=70 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Significance of Continuous Low-Dose Lenvatinib for the Treating of the Patients with Unresectable Thyroid Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=The tyrosine kinase inhibitor lenvatinib has been confirmed as an effective treatment option for patients with unresectable thyroid carcinoma. We conducted a retrospective analysis of the significance of the effect of continued lenvatinib treatment for the longest duration possible at a reasonable daily dose and with a minimum discontinuation period in 42 patients with unresectable thyroid carcinoma treated with lenvatinib between 2015 and 2020. A Cox proportional hazard model-based analysis revealed that the overall survival of the patients treated with a <8 mg/day mean dose of lenvatinib was significantly better than that of the patients treated with 8-24 mg/day (hazard ratio [HR] 0.38 for 1.14-4.54 mg/day, and HR 0.01 for 4.56-7.97 mg/day) adjusted for various factors (e.g., sex, age, drug interruption period). The cumulative dose of lenvatinib administered tended to be higher in the patients treated with low doses (< 8 mg/day) than in the patients treated with relatively high doses (8-24 mg/day). Considering its adverse events, the continuation of lenvatinib treatment with an adequate daily dose and drug interruption may help prolong the survival of patients with unresectable thyroid carcinoma. en-copyright= kn-copyright= en-aut-name=MurakamiDaizo en-aut-sei=Murakami en-aut-mei=Daizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimotoKohei en-aut-sei=Nishimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyamaruSatoru en-aut-sei=Miyamaru en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KadowakiTomoka en-aut-sei=Kadowaki en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaitoHaruki en-aut-sei=Saito en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakedaHiroki en-aut-sei=Takeda en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IseMomoko en-aut-sei=Ise en-aut-mei=Momoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuyamaKoichi en-aut-sei=Suyama en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OritaYorihisa en-aut-sei=Orita en-aut-mei=Yorihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Medical Oncology, Toranomon Hospital kn-affil= affil-num=10 en-affil=Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine kn-affil= en-keyword=thyroid carcinoma kn-keyword=thyroid carcinoma en-keyword=lenvatinib kn-keyword=lenvatinib en-keyword=adverse effect kn-keyword=adverse effect en-keyword=survival kn-keyword=survival END start-ver=1.4 cd-journal=joma no-vol=130 cd-vols= no-issue=7 article-no= start-page=1187 end-page=1195 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Pancreatic cancer is an aggressive, immunologically “cold” tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702).
Methods: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps).
Results: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection.
Conclusion: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer. en-copyright= kn-copyright= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KadowakiDaisuke en-aut-sei=Kadowaki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaYusuke en-aut-sei=Yoshida en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakamotoMasaki en-aut-sei=Sakamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamadaYuki en-aut-sei=Hamada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugimotoRyoma en-aut-sei=Sugimoto en-aut-mei=Ryoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YagiChiaki en-aut-sei=Yagi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhtaniTomoko en-aut-sei=Ohtani en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KumonKento en-aut-sei=Kumon en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=20 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=118 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hydrogen in Transplantation: Potential Applications and Therapeutic Implications en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hydrogen gas, renowned for its antioxidant properties, has emerged as a novel therapeutic agent with applications across various medical domains, positioning it as a potential adjunct therapy in transplantation. Beyond its antioxidative properties, hydrogen also exerts anti-inflammatory effects by modulating pro-inflammatory cytokines and signaling pathways. Furthermore, hydrogen's capacity to activate cytoprotective pathways bolsters cellular resilience against stressors. In recent decades, significant advancements have been made in the critical medical procedure of transplantation. However, persistent challenges such as ischemia-reperfusion injury (IRI) and graft rejection continue to hinder transplant success rates. This comprehensive review explores the potential applications and therapeutic implications of hydrogen in transplantation, shedding light on its role in mitigating IRI, improving graft survival, and modulating immune responses. Through a meticulous analysis encompassing both preclinical and clinical studies, we aim to provide valuable insights into the promising utility of hydrogen as a complementary therapy in transplantation. en-copyright= kn-copyright= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AgetaKohei en-aut-sei=Ageta en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HisamuraMasaki en-aut-sei=Hisamura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=hydrogen kn-keyword=hydrogen en-keyword=organ transplantation kn-keyword=organ transplantation en-keyword=ischemia reperfusion kn-keyword=ischemia reperfusion END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=4 article-no= start-page=e202301130 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Concise Synthesis of Thiazolo[4,5-b]indoles via Ring Switch/Cyclization Sequences en-subtitle= kn-subtitle= en-abstract= kn-abstract=The unexpected reactions of indoline hemiaminals affords 2,5-diaryl-4-hydroxythiazolines through a thioamidation/ring switch sequence. The key to success of this transformation is to use a thioamide as a thiazoline precursor under transient tautomeric control. This transformation features mild reaction conditions and good yields with broad functional group tolerance (17 examples, up to 99 % yield). Further transformations of the thiazolines provide a direct entry to dihydrothiazolo[4,5-b]indoles and thiazolo[4,5-b]indoles. en-copyright= kn-copyright= en-aut-name=YamadaKoji en-aut-sei=Yamada en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsubogoTetsu en-aut-sei=Tsubogo en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanazawaHikaru en-aut-sei=Kanazawa en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshizukaSayaka en-aut-sei=Ishizuka en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhyamaKoutaro en-aut-sei=Ohyama en-aut-mei=Koutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KaidaMasaki en-aut-sei=Kaida en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AbeTakumi en-aut-sei=Abe en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido kn-affil= affil-num=2 en-affil=Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido kn-affil= affil-num=3 en-affil=Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido kn-affil= affil-num=4 en-affil=Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido kn-affil= affil-num=5 en-affil=Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido kn-affil= affil-num=6 en-affil=Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido kn-affil= affil-num=7 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=hemiaminals kn-keyword=hemiaminals en-keyword=indoles kn-keyword=indoles en-keyword=ring-switch kn-keyword=ring-switch en-keyword=thiazolo[4.5-b]indoles kn-keyword=thiazolo[4.5-b]indoles en-keyword=thioamides kn-keyword=thioamides END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue= article-no= start-page=129536 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Direct evaluation of polarity of the ligand binding pocket in retinoid X receptor using a fluorescent solvatochromic agonist en-subtitle= kn-subtitle= en-abstract= kn-abstract=High selectivity of small-molecule drug candidates for their target molecule is important to minimize potential side effects. One factor that contributes to the selectivity is the internal polarity of the ligand-binding pocket (LBP) in the target molecule, but this is difficult to measure. Here, we first confirmed that the retinoid X receptor (RXR) agonist 6-(ethyl(1-isobutyl-2-oxo-4-(trifluoromethyl)-1,2-dihydroquinolin-7-yl)amino)nicotinic acid (NEt-iFQ, 1) exhibits fluorescence solvatochromism, i.e., its Stokes shift depends on the polarity of the solvent, and then we utilized this property to directly measure the internal polarity of the RXRα-LBP. The Stokes shift of 1 when bound to the RXRα-LBP corresponded to that of 1 in chloroform solution. This finding is expected to be helpful for designing RXR-selective ligands. A similar approach should be appliable to evaluate the internal polarity of the LBPs of other receptors. en-copyright= kn-copyright= en-aut-name=MiuraKizuku en-aut-sei=Miura en-aut-mei=Kizuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiharaMichiko en-aut-sei=Fujihara en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeMasaki en-aut-sei=Watanabe en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakamuraYuta en-aut-sei=Takamura en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawasakiMayu en-aut-sei=Kawasaki en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoShogo en-aut-sei=Nakano en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KakutaHiroki en-aut-sei=Kakuta en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka kn-affil= affil-num=6 en-affil=Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka kn-affil= affil-num=7 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=RXR kn-keyword=RXR en-keyword=Fluorescence kn-keyword=Fluorescence en-keyword=Solvatochromism kn-keyword=Solvatochromism en-keyword=Binding assay kn-keyword=Binding assay END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=6 article-no= start-page=635 end-page=645 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Nutritional Support Combined with Neuromuscular Electrical Stimulation on Muscle Strength and Thickness: A Randomized Controlled Trial in Healthy Young Adult Males en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the management of post-injury patients with activity limitations, methods to prevent musculoskeletal disorders and hasten recovery are important. This randomized controlled, single-blinded study was a preliminary investigation of the combined effect of nutritional support with neuromuscular electrical stimulation (NMES) on muscle strength and thickness. Healthy young adult males (median age, 21 years) were enrolled; each of their hands was randomly assigned to one of the following four groups: Placebo, Nutrition, NMES, and Nutrition + NMES. All participants received whey protein or placebo (3x/week for 6 weeks) and NMES training (3x/week for 6 weeks) on the abductor digiti minimi (ADM) muscle of either the left or right hand. ADM muscle strength and thickness were analyzed at baseline and at week 7. We analyzed 38 hands (9 Placebo, 10 Nutrition, 9 NMES, 10 Nutrition + NMES). There was significantly greater muscle strengthening in the Nutrition + NMES group compared to the Placebo group or the NMES group, but no significant difference in gain of muscle thickness. The combined intervention may be effective in improving muscle strength. Future clinical trials targeting various muscles after sports-related injuries are warranted. en-copyright= kn-copyright= en-aut-name=IkedaTomohiro en-aut-sei=Ikeda en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkamuraKazunori en-aut-sei=Okamura en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaMasaki en-aut-sei=Hasegawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaSatoshi en-aut-sei=Tanaka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanaiShusaku en-aut-sei=Kanai en-aut-mei=Shusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Rehabilitation Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima kn-affil= affil-num=3 en-affil=Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima kn-affil= affil-num=4 en-affil=Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima kn-affil= affil-num=5 en-affil=Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima kn-affil= en-keyword=whey protein kn-keyword=whey protein en-keyword=electrical stimulation kn-keyword=electrical stimulation en-keyword=muscle strength kn-keyword=muscle strength en-keyword=healthy volunteers kn-keyword=healthy volunteers END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=5 article-no= start-page=536 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of the accuracy of heart dose prediction by machine learning for selecting patients not requiring deep inspiration breath‑hold radiotherapy after breast cancer surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Increased heart dose during postoperative radiotherapy (RT) for left‑sided breast cancer (BC) can cause cardiac injury, which can decrease patient survival. The deep inspiration breath‑hold technique (DIBH) is becoming increasingly common for reducing the mean heart dose (MHD) in patients with left‑sided BC. However, treatment planning and DIBH for RT are laborious, time‑consuming and costly for patients and RT staff. In addition, the proportion of patients with left BC with low MHD is considerably higher among Asian women, mainly due to their smaller breast volume compared with that in Western countries. The present study aimed to determine the optimal machine learning (ML) model for predicting the MHD after RT to pre‑select patients with low MHD who will not require DIBH prior to RT planning. In total, 562 patients with BC who received postoperative RT were randomly divided into the trainval (n=449) and external (n=113) test datasets for ML using Python (version 3.8). Imbalanced data were corrected using synthetic minority oversampling with Gaussian noise. Specifically, right‑left, tumor site, chest wall thickness, irradiation method, body mass index and separation were the six explanatory variables used for ML, with four supervised ML algorithms used. Using the optimal value of hyperparameter tuning with root mean squared error (RMSE) as an indicator for the internal test data, the model yielding the best F2 score evaluation was selected for final validation using the external test data. The predictive ability of MHD for true MHD after RT was the highest among all algorithms for the deep neural network, with a RMSE of 77.4, F2 score of 0.80 and area under the curve‑receiver operating characteristic of 0.88, for a cut‑off value of 300 cGy. The present study suggested that ML can be used to pre‑select female Asian patients with low MHD who do not require DIBH for the postoperative RT of BC. en-copyright= kn-copyright= en-aut-name=KamizakiRyo en-aut-sei=Kamizaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaMasahiro en-aut-sei=Kuroda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Al‑HammadWlla en-aut-sei=Al‑Hammad en-aut-mei=Wlla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TekikiNouha en-aut-sei=Tekiki en-aut-mei=Nouha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshizakaHinata en-aut-sei=Ishizaka en-aut-mei=Hinata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurodaKazuhiro en-aut-sei=Kuroda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=TanabeYoshinori en-aut-sei=Tanabe en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=BarhamMajd en-aut-sei=Barham en-aut-mei=Majd kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SugiantoIrfan en-aut-sei=Sugianto en-aut-mei=Irfan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakamitsuYuki en-aut-sei=Nakamitsu en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HiranoMasaki en-aut-sei=Hirano en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MutoYuki en-aut-sei=Muto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IharaHiroki en-aut-sei=Ihara en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SugiyamaSoichi en-aut-sei=Sugiyama en-aut-mei=Soichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An‑Najah National University kn-affil= affil-num=11 en-affil=Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University kn-affil= affil-num=12 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Proton Beam Therapy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=BC kn-keyword=BC en-keyword=RT kn-keyword=RT en-keyword=heart dose kn-keyword=heart dose en-keyword=ML kn-keyword=ML en-keyword=DNN kn-keyword=DNN en-keyword=DIBH kn-keyword=DIBH END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=5 article-no= start-page=545 end-page=552 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endoscopic Manifestations and Clinical Characteristics of Localized Gastric Light-Chain Amyloidosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaShouichi en-aut-sei=Tanaka en-aut-mei=Shouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=NishimuraMamoru en-aut-sei=Nishimura en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuzukiTakao en-aut-sei=Tsuzuki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyaharaKoji en-aut-sei=Miyahara en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NegishiShin en-aut-sei=Negishi en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhyaShogen en-aut-sei=Ohya en-aut-mei=Shogen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Okayama City Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Kawaguchi Medical Clinic kn-affil= affil-num=9 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=gastric lesion kn-keyword=gastric lesion en-keyword=amyloidosis kn-keyword=amyloidosis en-keyword=light chain kn-keyword=light chain END start-ver=1.4 cd-journal=joma no-vol=263 cd-vols= no-issue= article-no= start-page=133 end-page=166 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230816 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The universal factorial Hall–Littlewood P- and Q-functions en-subtitle= kn-subtitle= en-abstract= kn-abstract=We introduce factorial analogues of the ordinary Hall–Littlewood P- and Q-polynomials, which we call the factorial Hall–Littlewood P- and Q-polynomials. Using the universal formal group law, we further generalize these polynomials to the universal factorial Hall–Littlewood P- and Q-functions. We show that these functions satisfy the vanishing property which the ordinary factorial Schur S-, P-, and Q-polynomials have. By the vanishing property, we derive the Pieri-type formula and a certain generalization of the classical hook formula. We then characterize our functions in terms of Gysin maps from flag bundles in complex cobordism theory. Using this characterization and Gysin formulas for flag bundles, we obtain generating functions for the universal factorial Hall–Littlewood P- and Q-functions. Using our generating functions, we show that our factorial Hall–Littlewood P- and Q-polynomials have a certain cancellation property. Further applications such as Pfaffian formulas for K-theoretic factorial Q-polynomials are also given. en-copyright= kn-copyright= en-aut-name=NakagawaMasaki en-aut-sei=Nakagawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaruseHiroshi en-aut-sei=Naruse en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Education Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Education University of Yamanashi kn-affil= en-keyword=factorial Hall-Littlewood P-and Q-functions kn-keyword=factorial Hall-Littlewood P-and Q-functions en-keyword=generating func-tions kn-keyword=generating func-tions en-keyword=formal group laws kn-keyword=formal group laws en-keyword=complex cobordism theory kn-keyword=complex cobordism theory en-keyword=Gysin formulas kn-keyword=Gysin formulas END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=20050930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=親和するよう修飾したテロメラーゼ特異的選択的増殖アデノウイルスOBP-405('Telomelysin-RGD')による腫瘍融解の増強 kn-title=Enhanced oncolysis by a tropism-modified telomerase-specific replication-selective adenoviral agent OBP-405 ('Telomelysin-RGD') en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakiMasaki en-aut-sei=Taki en-aut-mei=Masaki kn-aut-name=滝正樹 kn-aut-sei=滝 kn-aut-mei=正樹 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=236 cd-vols= no-issue=3 article-no= start-page=864 end-page=877 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220817 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A tonoplast‐localized magnesium transporter is crucial for stomatal opening in Arabidopsis under high Mg2+ conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plant stomata play an important role in CO2 uptake for photosynthesis and transpiration, but the mechanisms underlying stomatal opening and closing under changing environmental conditions are still not completely understood.
Through large-scale genetic screening, we isolated an Arabidopsis mutant (closed stomata2 (cst2)) that is defective in stomatal opening. We cloned the causal gene (MGR1/CST2) and functionally characterized this gene.
The mutant phenotype was caused by a mutation in a gene encoding an unknown protein with similarities to the human magnesium (Mg2+) efflux transporter ACDP/CNNM. MGR1/CST2 was localized to the tonoplast and showed transport activity for Mg2+. This protein was constitutively and highly expressed in guard cells. Knockout of this gene resulted in stomatal closing, decreased photosynthesis and growth retardation, especially under high Mg2+ conditions, while overexpression of this gene increased stomatal opening and tolerance to high Mg2+ concentrations. Furthermore, guard cell-specific expression of MGR1/CST2 in the mutant partially restored its stomatal opening.
Our results indicate that MGR1/CST2 expression in the leaf guard cells plays an important role in maintaining cytosolic Mg2+ concentrations through sequestering Mg2+ into vacuoles, which is required for stomatal opening, especially under high Mg2+ conditions. en-copyright= kn-copyright= en-aut-name=InoueShin‐ichiro en-aut-sei=Inoue en-aut-mei=Shin‐ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiMaki en-aut-sei=Hayashi en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangSheng en-aut-sei=Huang en-aut-mei=Sheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokoshoKengo en-aut-sei=Yokosho en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotohEiji en-aut-sei=Gotoh en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkematsuShuka en-aut-sei=Ikematsu en-aut-mei=Shuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkumuraMasaki en-aut-sei=Okumura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=KamuraTakumi en-aut-sei=Kamura en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KinoshitaToshinori en-aut-sei=Kinoshita en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=2 en-affil=Division of Biological Science, Graduate School of Science, Nagoya 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=Department of Forest Environmental Sciences, Faculty of Agriculture, Kyushu University kn-affil= affil-num=6 en-affil=Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University kn-affil= affil-num=7 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=8 en-affil=Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=9 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=10 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=11 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=ACDP kn-keyword=ACDP en-keyword=CNNM kn-keyword=CNNM en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=magnesium transport kn-keyword=magnesium transport en-keyword=plant growth kn-keyword=plant growth en-keyword=stomatal opening kn-keyword=stomatal opening END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=7 article-no= start-page=e0288175 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Augmented reality-based affective training for improving care communication skill and empathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=It is important for caregivers of people with dementia (PwD) to have good patient communication skills as it has been known to reduce the behavioral and psychological symptoms of dementia (BPSD) of PwD as well as caregiver burnout. However, acquiring such skills often requires one-on-one affective training, which can be costly. In this study, we propose affective training using augmented reality (AR) for supporting the acquisition of such skills. The system uses see-through AR glasses and a nursing training doll to train the user in both practical nursing skills and affective skills such as eye contact and patient communication. The experiment was conducted with 38 nursing students. The participants were assigned to either the Doll group, which only used a doll for training, or the AR group, which used both a doll and the AR system. The results showed that eye contact significantly increased and the face-to-face distance and angle decreased in the AR group, while the Doll group had no significant difference. In addition, the empathy score of the AR group significantly increased after the training. Upon analyzing the correlation between personality and changes of physical skills, we found a significant positive correlation between the improvement rate of eye contact and extraversion in the AR group. These results demonstrated that affective training using AR is effective for improving caregivers' physical skills and their empathy for their patients. We believe that this system will be beneficial not only for dementia caregivers but for anyone looking to improve their general communication skills. en-copyright= kn-copyright= en-aut-name=NakazawaAtsushi en-aut-sei=Nakazawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwamotoMiyuki en-aut-sei=Iwamoto en-aut-mei=Miyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurazumeRyo en-aut-sei=Kurazume en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NunoiMasato en-aut-sei=Nunoi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiMasaki en-aut-sei=Kobayashi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HondaMiwako en-aut-sei=Honda en-aut-mei=Miwako 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 Advanced Fibro-Science, Kyoto Institute of Technology kn-affil= affil-num=3 en-affil=Faculty of Information Science and Electrical Engineering, Kyushu University kn-affil= affil-num=4 en-affil=School of Human Sciences, Sugiyama Jogakuen University kn-affil= affil-num=5 en-affil=Division of geriatric medicine, Rochester Regional Health System kn-affil= affil-num=6 en-affil=Division of Geriatric Research, National Hospital Organization Tokyo Medical Center kn-affil= END start-ver=1.4 cd-journal=joma no-vol=299 cd-vols= no-issue=4 article-no= start-page=104587 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ATP and its metabolite adenosine cooperatively upregulate the antigen-presenting molecules on dendritic cells leading to IFN-gamma production by T cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells (DCs) present foreign antigens to T cells via the major histocompatibility complex (MHC), thereby inducing acquired immune responses. ATP accumulates at sites of inflammation or in tumor tissues, which triggers local inflammatory responses. However, it remains to be clarified how ATP modulates the functions of DCs. In this study, we investigated the effects of extracellular ATP on mouse bone marrow- derived dendritic cells (BMDCs) as well as the potential for subsequent T cell activation. We found that high concentrations of ATP (1 mM) upregulated the cell surface expression levels of MHC-I, MHC-II, and co-stimulatory molecules CD80 and CD86 but not those of co-inhibitory molecules PD-L1 and PD-L2 in BMDCs. Increased surface expression of MHC-I, MHC-II, CD80, and CD86 was inhibited by a pan-P2 receptor antagonist. In addition, the upregulation of MHC-I and MHC-II expression was inhibited by an adenosine P1 receptor antagonist and by inhibitors of CD39 and CD73, which metabolize ATP to adenosine. These results suggest that adenosine is required for the ATP-induced upregulation of MHC-I and MHC-II. In the mixed leukocyte reaction assay, ATP-stimulated BMDCs activated CD4 and CD8T cells and induced interferon-gamma (IFN-gamma) production by these T cells. Collectively, these results suggest that high concentrations of extracellular ATP upregulate the expression of antigenpresenting and co-stimulatory molecules but not that of coinhibitory molecules in BMDCs. Cooperative stimulation of ATP and its metabolite adenosine was required for the upregulation of MHC-I and MHC-II. These ATP-stimulated BMDCs induced the activation of IFN-gamma-producing T cells upon antigen presentation. 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=OnishiHiroka en-aut-sei=Onishi en-aut-mei=Hiroka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkadaYuki en-aut-sei=Ikada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasakiKento en-aut-sei=Masaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaSatoshi en-aut-sei=Tanaka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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 Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=4 article-no= start-page=582 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230326 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Effect of Medical Cooperation in the CKD Patients: 10-Year Multicenter Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. Methods: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. Results: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 +/- 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). Conclusion: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD. en-copyright= kn-copyright= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaeshimaYohei en-aut-sei=Maeshima en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkuyamaYuka en-aut-sei=Okuyama en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtakaNozomu en-aut-sei=Otaka en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UjikeHaruyo en-aut-sei=Ujike en-aut-mei=Haruyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaKeiko en-aut-sei=Tanaka en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitagawaMasashi en-aut-sei=Kitagawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KinomuraMasaru en-aut-sei=Kinomura en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OtaKosuke en-aut-sei=Ota en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaruyamaKeisuke en-aut-sei=Maruyama en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HiramatsuMakoto en-aut-sei=Hiramatsu en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OshiroYoshiyuki en-aut-sei=Oshiro en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MoriokaShigeru en-aut-sei=Morioka en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TakiueKeiichi en-aut-sei=Takiue en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OmoriKazuyoshi en-aut-sei=Omori en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FukushimaMasaki en-aut-sei=Fukushima en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=GamouNaoyuki en-aut-sei=Gamou en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HirataHiroshi en-aut-sei=Hirata en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=5 en-affil=Kagawa Prefectural Central Hospital kn-affil= affil-num=6 en-affil=Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=National Hospital Organization Okayama Medical Center kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Okayama Saiseikai General Hospital kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=National Hospital Organization Okayama Medical Center kn-affil= affil-num=17 en-affil=Okayama Saiseikai General Hospital kn-affil= affil-num=18 en-affil=Okayama Saiseikai General Hospital, kn-affil= affil-num=19 en-affil=Kawasaki Medical School General Medical Center kn-affil= affil-num=20 en-affil=Okayama Central Hospital kn-affil= affil-num=21 en-affil=Okayama City Hospital kn-affil= affil-num=22 en-affil=Shigei Medical Research Hospital kn-affil= affil-num=23 en-affil=Shigei Medical Research Hospital kn-affil= affil-num=24 en-affil=Japanese Red Cross Okayama Hospital kn-affil= affil-num=25 en-affil=Akebono Clinic kn-affil= affil-num=26 en-affil=Sato Clinic kn-affil= affil-num=27 en-affil=Okayama University kn-affil= affil-num=28 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=chronic kidney disease (CKD) kn-keyword=chronic kidney disease (CKD) en-keyword=medical cooperation kn-keyword=medical cooperation en-keyword=patient care team kn-keyword=patient care team en-keyword=OCKD-NET kn-keyword=OCKD-NET END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=3 article-no= start-page=109 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=2023124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Quantitative evaluation of the reduction of distortion and metallic artifacts in magnetic resonance images using the multiacquisition variable‑resonance image combination selective sequence en-subtitle= kn-subtitle= en-abstract= kn-abstract=Magnetic resonance imaging (MRI) is superior to computed tomography (CT) in determining changes in tissue structure, such as those observed following inflammation and infection. However, when metal implants or other metal objects are present, MRI exhibits more distortion and artifacts compared with CT, which hinders the accurate measurement of the implants. A limited number of reports have examined whether the novel MRI sequence, multiacquisition variable-resonance image combination selective (MAVRIC SL), can accurately measure metal implants without distortion. Therefore, the present study aimed to demonstrate whether MAVRIC SL could accurately measure metal implants without distortion and whether the area around the metal implants could be well delineated without artifacts. An agar phantom containing a titanium alloy lumbar implant was used for the present study and was imaged using a 3.0 T MRI machine. A total of three imaging sequences, namely MAVRIC SL, CUBE and magnetic image compilation (MAGiC), were applied and the results were compared. Distortion was evaluated by measuring the screw diameter and distance between the screws multiple times in the phase and frequency directions by two different investigators. The artifact region around the implant was examined using a quantitative method following standardization of the phantom signal values. It was revealed that MAVRIC SL was a superior sequence compared with CUBE and MAGiC, as there was significantly less distortion, a lack of bias between the two different investigators and significantly reduced artifact regions. These results suggested the possibility of utilizing MAVRIC SL for follow-up to observe metal implant insertions. en-copyright= kn-copyright= en-aut-name=HiranoMasaki en-aut-sei=Hirano en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MutoYuki en-aut-sei=Muto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurodaMasahiro en-aut-sei=Kuroda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraYuta en-aut-sei=Fujiwara en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasakiTomoaki en-aut-sei=Sasaki en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurodaKazuhiro en-aut-sei=Kuroda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamizakiRyo en-aut-sei=Kamizaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ImajohSatoshi en-aut-sei=Imajoh en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanabeYoshinori en-aut-sei=Tanabe en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=E. Al-HammadWlla en-aut-sei=E. Al-Hammad en-aut-mei=Wlla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamitsuYuki en-aut-sei=Nakamitsu en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShimizuYudai en-aut-sei=Shimizu en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=SugiantoIrfan en-aut-sei=Sugianto en-aut-mei=Irfan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=O. BamgboseBabatunde en-aut-sei=O. Bamgbose en-aut-mei=Babatunde kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Clinical Radiology Service, Okayama Central Hospital kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University, Okayama 700‑8558, Japan kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University, Okayama, 770‑8558, Japan kn-affil= affil-num=14 en-affil=Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University kn-affil= affil-num=15 en-affil=Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University kn-affil= affil-num=16 en-affil=Department of Oral Diagnostic Sciences, Faculty of Dentistry, Bayero University kn-affil= en-keyword=MAVRIC SL kn-keyword=MAVRIC SL en-keyword=metal artifacts kn-keyword=metal artifacts en-keyword=implant kn-keyword=implant en-keyword=phantom kn-keyword=phantom en-keyword=MRI kn-keyword=MRI END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=2 article-no= start-page=209 end-page=213 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Locally Advanced Rectal Cancer Invading the Gluteus Maximus Muscle Completely Responded to Total Neoadjuvant Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 70-year-old male with anal pain and fever was diagnosed with rectal cancer perforation and abscess in the right gluteus maximus (GM) muscle. He underwent a transverse colon colostomy followed by preoperative capecitabine+oxaliplatin. Some local control was achieved but a residual abscess was observed in the right GM muscle. To secure circumferential resection margin by tumor reduction, he received chemoradiotherapy as total neoadjuvant therapy (TNT) and underwent laparoscopic abdominoperineal resection, D3 lymph node dissection, combined coccyx resection, and partial resection of the right GM muscle. The skin defect and pelvic dead space were filled with a right lateral vastus lateral great muscle flap. Histopathologically, the resected specimen showed no tumor cells in the primary tumor or lymph nodes, indicating a pathological complete response (pCR). This case suggests that TNT might improve the R0 resection and pCR rates and overall survival. en-copyright= kn-copyright= en-aut-name=SakamotoMasaki en-aut-sei=Sakamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=ShigeyasuKunitoshi kn-aut-sei=Shigeyasu kn-aut-mei=Kunitoshi aut-affil-num=3 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=4 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of 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= en-keyword=locally advanced rectal cancer kn-keyword=locally advanced rectal cancer en-keyword=total neoadjuvant therapy kn-keyword=total neoadjuvant therapy en-keyword=lateral vastus lateral great muscle flap kn-keyword=lateral vastus lateral great muscle flap END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=2 article-no= start-page=169 end-page=177 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predictive Factors for Recovery from Alcoholic Liver Failure en-subtitle= kn-subtitle= en-abstract= kn-abstract=Alcoholic liver disease is a risk factor for non-virus-related hepatocellular carcinoma (HCC), which is increasing in prevalence. This study aimed to identify the factors for recovery from alcoholic liver failure. Sixty-two consecutive patients hospitalized for alcoholic liver failure at Okayama City Hospital were enrolled. The characteristics of patients who survived to the 1-month follow-up and whose liver function improved to Child–Pugh A at 3 months (CPA3) and 12 months (CPA12) were compared with the rest of the patients. The survivors at 1 month (50 patients) were significantly younger than the deceased patients and had better liver and renal function with higher levels of γ-glutamyl transferase (GGT). The same factors, except renal function, were correlated with achieving CPA3. High AST, ALT, and GGT levels as well as short spleen length, total abstinence, and good Child–Pugh scores at admission were identified as factors for achieving CPA12. The extent of alcohol intake before admission was not identified as a risk factor in any analysis. In conclusion, baseline liver function is crucial for survival and achieving CPA3, whereas high transaminase and γ-GTP levels, the absence of splenomegaly, and total abstinence are significant factors for achieving CPA12. en-copyright= kn-copyright= en-aut-name=InoueKanae en-aut-sei=Inoue en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujitaRio en-aut-sei=Fujita en-aut-mei=Rio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaharaTakatoshi en-aut-sei=Nagahara en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurakamiShiho en-aut-sei=Murakami en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaiYuta en-aut-sei=Nagai en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriwakeRina en-aut-sei=Moriwake en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyakeNozomi en-aut-sei=Miyake en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WakutaAkiko en-aut-sei=Wakuta en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KariyamaKazuya en-aut-sei=Kariyama en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimuraMamoru en-aut-sei=Nishimura en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= en-keyword=alcoholic liver failure kn-keyword=alcoholic liver failure en-keyword=risk factors kn-keyword=risk factors en-keyword=recovery kn-keyword=recovery END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=2 article-no= start-page=131 end-page=137 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Venous Thromboembolism in Eating Disorders: A Retrospective Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Eating disorders (EDs) are associated with a high mortality rate. Patients with EDs often experience severe dehydration due to food restriction and/or vomiting. Severely underweight patients are often prescribed bed rest during inpatient care to reduce their energy consumption, and they may thus develop multiple risk factors for venous thromboembolism (VTE). We compared the clinical features of ED inpatients with VTE to those of ED inpatients without VTE. Seventy-one inpatients with ED were treated at Okayama University Hospital’s psychiatric ward in 2016-2020; five were experienced a VTE. Compared to the non-VTE group, the VTE group’s median age and disease duration were greater and the median body mass index (BMI) was lower. The VTE group’s D-dimer peak values were > 5 mg/L. Physical restraint and central venous catheter use were associated with VTE. Longer ED duration and lower BMI might be risk factors for VTE. To make inpatient treatment for ED safer, it is important to avoid the use of physical restraints and central venous catheters. Continuous D-dimer monitoring is necessary for the early detection of VTE in ED patients at high risk of VTE. en-copyright= kn-copyright= en-aut-name=SendaMayuko en-aut-sei=Senda en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaNorihito en-aut-sei=Yamada en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=eating disorder kn-keyword=eating disorder en-keyword=anorexia nervosa kn-keyword=anorexia nervosa en-keyword=venous thromboembolism kn-keyword=venous thromboembolism en-keyword=deep vein thrombosis kn-keyword=deep vein thrombosis END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevalence of transthyretin amyloidosis among heart failure patients with preserved ejection fraction in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims Heart failure with preserved ejection fraction (HFpEF), which is caused by wide various conditions, has become a major public health problem. Transthyretin amyloid cardiomyopathy (ATTR-CM), which is thought to be an underdiagnosed disease, can cause HFpEF. Non-invasive diagnosis using 99mTechnetium (Tc)-pyrophosphate (PYP) scintigraphy enables accurate diagnosis of ATTR-CM. The aim of this study was to clarify the prevalence and characteristics of ATTR-CM among Japanese patients with HFpEF.
Methods and results This study was a multicentre, prospective, observational study conducted in Japan. We enrolled 373 patients with HFpEF [left ventricular (LV) ejection fraction ≥50%] aged ≥65 years who were admitted to the department of cardiology from September 2018 to January 2022. A 99mTc-PYP scintigraphy scan was performed during admission in all eligible patients. Cardiac 99mTc-PYP retention was graded according to a previously reported visual scale ranging from 0 to 3 points. The scan was considered positive when it revealed moderate-to-severe 99mTc-PYP uptake (Grade 2–3) in both ventricles. Patients were divided into ATTR-CM and non-ATTR-CM patients according to positive (Grade 2–3) or negative (Grade 0–1) 99mTc-PYP scintigraphy, respectively. Medical history, blood tests, electrocardiogram, echocardiography, and magnetic resonance imaging in the two groups of patients were compared. Among the 373 patients with HFpEF, 53 patients (14.2%; 95% confidence interval: 10.7–17.7) showed positive uptake on 99mTc-PYP scintigraphy. An endomyocardial biopsy was performed in 32 patients and confirmed amyloidosis in all cases. There were no significant differences between the two groups in age, severity of heart failure as assessed by the New York Heart Association (NYHA) functional classification, renal function values, left ventricular ejection fraction, and tricuspid regurgitant pressure gradient (ATTR-CM, n = 53 vs. non-ATTR-CM, n = 320). Patients in the ATTR-CM group had a higher N-terminal pro-brain natriuretic peptide level [2314 (1081–3398) vs. 900 (415–1828), P < 0.001], higher sensitive troponin T level (0.074 ± 0.049 vs. 0.035 ± 0.038, P < 0.001), and higher mean LV maximal wall thickness [12.5 (11–14) vs. 10.5 (9.5–11.5), P < 0.001].
Conclusions ATTR-CM is an underdiagnosed disease with a significant prevalence in Japanese patients with HFpEF. This study showed that results of examinations for ATTR-CM patients appear to be worse than those for non-ATTR-CM patients, but clinical severities of heart failure as assessed by the NYHA functional classification are similar in ATTR-CM and non-ATTR-CM patients, and the clinical overlap between ATTR-CM and non-ATTR-CM is high. en-copyright= kn-copyright= en-aut-name=NaitoTakanori en-aut-sei=Naito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AbeYukio en-aut-sei=Abe en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeHiroyuki en-aut-sei=Watanabe en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakuragiSatoru en-aut-sei=Sakuragi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaYusuke en-aut-sei=Katayama en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KiharaHajime en-aut-sei=Kihara en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkizakiAtsutaka en-aut-sei=Okizaki en-aut-mei=Atsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawaiYusuke en-aut-sei=Kawai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshikawaMasaki en-aut-sei=Yoshikawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakaishiAtsushi en-aut-sei=Takaishi en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujioHideki en-aut-sei=Fujio en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtsukaHiroaki en-aut-sei=Otsuka en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OguraSoichiro en-aut-sei=Ogura en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ATTR HFpEF Registry Investigators en-aut-sei=ATTR HFpEF Registry Investigators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiology, Osaka City General Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Tokyo Bay Urayasu Ichikawa Medical Center kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Kihara Cardiovascular Clinic kn-affil= affil-num=8 en-affil=Department of Radiology, Asahikawa Medical University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama City Hospital kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=11 en-affil=Department of Cardiology, Mitoyo General Hospital kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil= kn-affil= en-keyword=Transthyretin amyloidosis kn-keyword=Transthyretin amyloidosis en-keyword=Heart failure kn-keyword=Heart failure en-keyword=Scintigraphy kn-keyword=Scintigraphy en-keyword=Left ventricular hypertrophy kn-keyword=Left ventricular hypertrophy END start-ver=1.4 cd-journal=joma no-vol=85 cd-vols= no-issue=4 article-no= start-page=436 end-page=480 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Poor vaccine responsiveness towards third-dose mRNA vaccine of COVID-19 in Japanese older people en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HikitaTakao en-aut-sei=Hikita en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HabuTomohiro en-aut-sei=Habu en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsadaMasaki en-aut-sei=Asada en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University 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=Departments of Medical Education, Kurashiki Central Hospital kn-affil= affil-num=5 en-affil=Department of Epidemiology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=1 article-no= start-page=75 end-page=80 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Scattered Tiny Whitish Protrusions in the Stomach Are a Clue to the Diagnosis of Autoimmune Gastritis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Herein, we report two patients with autoimmune gastritis who had undergone multiple esophagogastroduodenoscopy procedures for 17 and 9 years, respectively, before their diagnosis. Instead, they had been diagnosed with and treated for Helicobacter pylori-associated gastritis. The correct diagnosis was made when scatterings of tiny whitish protrusions in the gastric mucosa were detected on esophagogastroduodenoscopy. Our findings suggest that scattered tiny whitish bumps may be a clue to the diagnosis of autoimmune gastritis. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=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=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanzakiHiromitsu en-aut-sei=Kanzaki en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=autoimmune gastritis kn-keyword=autoimmune gastritis en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=scattered lesions kn-keyword=scattered lesions en-keyword=small white protrusions kn-keyword=small white protrusions en-keyword=mucosal lesions kn-keyword=mucosal lesions END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=1 article-no= start-page=673 end-page=680 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characteristics of Postoperative Patients with Breast Cancer Aged 65 Years and Older en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: This study aimed to compare postoperative patients with breast cancer aged >= 65 years with those aged <65 years and clarify the characteristics of postoperative patients with breast cancer aged >= 65. Methods: In total, 376 patients in whom we were able to evaluate survey items one month after surgery were included in the study. Comorbidity, including diabetes mellitus and hypertension, shoulder range of motion (ROM), upper-limb function, and psychological problems, was evaluated. Results: Hypertension and diabetes mellitus were significantly higher in patients aged >= 65 years (the elderly group) than in those aged <65 years (the non-elderly group) (p < 0.05). Preoperative shoulder flexion ROM was significantly restricted in the elderly group compared with the non-elderly group (p < 0.05). Preoperative shoulder abduction ROM was significantly restricted in the elderly group compared with the non-elderly group (p < 0.05). At one month after surgery, upper-limb function was more impaired in the non-elderly group than in the elderly group (p < 0.05). In both groups, both ROM and upper-limb function were significantly impaired one month after surgery compared with before surgery (p < 0.05). Conclusions: Postoperative patients with breast cancer aged >= 65 years should be careful about risk management and intervention during rehabilitation. Preoperative evaluation of shoulder ROM should be performed because patients aged >= 65 years have limited ROM before surgery. en-copyright= kn-copyright= en-aut-name=AkezakiYoshiteru en-aut-sei=Akezaki en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikuuchiMasato en-aut-sei=Kikuuchi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TominagaRitsuko en-aut-sei=Tominaga en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurokawaHideaki en-aut-sei=Kurokawa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoMasaki en-aut-sei=Okamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=OhsumiShozo en-aut-sei=Ohsumi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugiharaShinsuke en-aut-sei=Sugihara en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Physical Therapy, Kochi Professional University of Rehabilitation kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center, kn-affil= affil-num=6 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center, kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=10 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=elderly kn-keyword=elderly en-keyword=comorbidity kn-keyword=comorbidity en-keyword=upper-limb function kn-keyword=upper-limb function en-keyword=rehabilitation kn-keyword=rehabilitation END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue= article-no= start-page=18 end-page=31 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The beginning date of wet rice cultivation at the of Okayama University site: Tree ring oxygen isotope dating and radiocarbon 14 age of weirs from the mid-I stage of the Yayoi period kn-title=岡山大学構内遺跡における水田稲作の開始年代 ―Ⅰ期中段階の堰の酸素同位体比年輪年代と炭素14年代― en-subtitle= kn-subtitle= en-abstract= kn-abstract=This article clarifies the date when paddy field rice cultivation began at the archaeological site located within the Okayama University campus. The analysis used tree ring oxygen isotope dating and radiocarbon dating. When the oxygen isotope ratios of wood used in paddy weirs detected in the 23rd excavation season were examined, peaks could be seen in two places: in the 10th century BC and the 6th century BC. Since the weir was accompanied by mid-I stage Yayoi pottery, which was dated to the 6th century BC using radiocarbon dating, tree ring dating determined that the weir was made from wood cut down soon after 540 BC. Therefore, it was reaffirmed that one of the points of the mid-I stage can be dated to the middle of the 6th century BC.
Next is the age of the early-I stage, when paddy field rice cultivation began on the Okayama Plain. In the Tsuruba area of the Nishikawazu archaeological site in Shimane Prefecture, where paddy field rice cultivation is thought to have begun at the same time as on the Okayama Plain, tree ring oxygen isotope dating of wood accompanied by early-I stage pottery has been reported. The date of 649 BC date means that one of the earliest stages of the early-I period dates to the middle of the 7th century BC. Therefore, we reaffirmed the view that paddy rice cultivation in the Chugoku region, such as Okayama and Shimane, began in the 7th century BC.
It also became clear that the beginning of paddy field rice cultivation in the Chugoku region occurred at a time when the climate that had been the base of cold in the 10th century BC gradually warmed and the relatively humid climate began to turn to arid. en-copyright= kn-copyright= en-aut-name=FUJIOShinichiro en-aut-sei=FUJIO en-aut-mei=Shinichiro kn-aut-name=藤尾慎一郎 kn-aut-sei=藤尾 kn-aut-mei=慎一郎 aut-affil-num=1 ORCID= en-aut-name=SAKAMOTOMinoru en-aut-sei=SAKAMOTO en-aut-mei=Minoru kn-aut-name=坂本稔 kn-aut-sei=坂本 kn-aut-mei=稔 aut-affil-num=2 ORCID= en-aut-name=SANOMasaki en-aut-sei=SANO en-aut-mei=Masaki kn-aut-name=佐野雅規 kn-aut-sei=佐野 kn-aut-mei=雅規 aut-affil-num=3 ORCID= affil-num=1 en-affil=The National Museum of Japanese History, School of Cultural and Social Studies, The Graduate University for Advanced Studies kn-affil= affil-num=2 en-affil=The National Museum of Japanese History, School of Cultural and Social Studies, The Graduate University for Advanced Studies kn-affil= affil-num=3 en-affil=Graduate School of Environmental Studies, Nagoya University kn-affil= en-keyword=土器付着炭化物：carbides adhering to pottery kn-keyword=土器付着炭化物：carbides adhering to pottery en-keyword=酸素同位体比年輪年代法：tree ring oxygen isotope dating kn-keyword=酸素同位体比年輪年代法：tree ring oxygen isotope dating en-keyword=炭素14年代法：radiocarbon dating kn-keyword=炭素14年代法：radiocarbon dating en-keyword=岡山大学構内遺跡：the Okayama University site kn-keyword=岡山大学構内遺跡：the Okayama University site en-keyword=弥生前期：the early Yayoi period kn-keyword=弥生前期：the early Yayoi period en-keyword=水田稲作：wet rice cultivation kn-keyword=水田稲作：wet rice cultivation en-keyword=堰：weirs kn-keyword=堰：weirs END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=6 article-no= start-page=679 end-page=688 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy and Safety of Three-dimensional Conformal Radiotherapy for Macroscopic Vascular Invasion of Hepatocellular Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chemotherapy is insufficient to treat macroscopic vascular invasion (MVI) of hepatocellular carcinoma (HCC). We retrospectively investigated the treatment outcomes of patients who underwent three-dimensional conformal radiotherapy (3D-CRT) for HCC MVI and analyzed prognostic factors by multivariate analysis using a Cox proportional hazard model. Sixty-five patients were studied. MVI sites were the portal vein (n=48 patients), portal and hepatic veins (n=8), and hepatic vein (n=9). The median irradiation dose was 50 Gy. The median survival time (MST) was 7.5 months. Performance status 2 or 3, modified albumin-bilirubin grade 2b or 3, and massive/diffuse type were poor prognostic factors. Nineteen patients (29%) with a treatment effect of 3 or 4 (≥ 50% of tumor necrosis or regression) at the irradiation sites according to the Response Evaluation Criteria in Cancer of the Liver showed longer survival than those with an effect of 1 or 2 (MST 18.7 vs. 5.9 months, p<0.001). No treatment-related death occurred. The hepatic function reserve was preserved in more than 70% of patients. 3D-CRT controlled HCC MVI safely and was suggested to be a good treatment option. en-copyright= kn-copyright= en-aut-name=AsagiAkinori en-aut-sei=Asagi en-aut-mei=Akinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakaguchiChihiro en-aut-sei=Sakaguchi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NadanoSeijin en-aut-sei=Nadano en-aut-mei=Seijin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishinaTomohiro en-aut-sei=Nishina en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamamotoYasushi en-aut-sei=Hamamoto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KataokaMasaaki en-aut-sei=Kataoka en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamashitaNatsumi en-aut-sei=Yamashita en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanimizuMasahito en-aut-sei=Tanimizu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HyodoIchinosuke en-aut-sei=Hyodo en-aut-mei=Ichinosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=2 en-affil=Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=3 en-affil=Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Radiation Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Radiology, Saiseikai Imabari Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Research Center, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=macroscopic vascular invasion kn-keyword=macroscopic vascular invasion en-keyword=portal vein tumor thrombosis kn-keyword=portal vein tumor thrombosis en-keyword=hepatic vein tumor thrombosis kn-keyword=hepatic vein tumor thrombosis en-keyword=three-dimensional conformal radiotherapy kn-keyword=three-dimensional conformal radiotherapy END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=15628 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220917 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer stem cells induced by chronic stimulation with prostaglandin E2 exhibited constitutively activated PI3K axis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Previously, our group has demonstrated establishment of Cancer Stem Cell (CSC) models from stem cells in the presence of conditioned medium of cancer cell lines. In this study, we tried to identify the factors responsible for the induction of CSCs. Since we found the lipid composition could be traced to arachidonic acid cascade in the CSC model, we assessed prostaglandin E2 (PGE2) as a candidate for the ability to induce CSCs from induced pluripotent stem cells (iPSCs). Mouse iPSCs acquired the characteristics of CSCs in the presence of 10 ng/mL of PGE2 after 4 weeks. Since constitutive Akt activation and pik3cg overexpression were found in the resultant CSCs, of which growth was found independent of PGE2, chronic stimulation of the receptors EP-2/4 by PGE2 was supposed to induce CSCs from iPSCs through epigenetic effect. The bioinformatics analysis of the next generation sequence data of the obtained CSCs proposed not only receptor tyrosine kinase activation by growth factors but also extracellular matrix and focal adhesion enhanced PI3K pathway. Collectively, chronic stimulation of stem cells with PGE2 was implied responsible for cancer initiation enhancing PI3K/Akt axis. en-copyright= kn-copyright= en-aut-name=MinematsuHideki en-aut-sei=Minematsu en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AfifySaid M. en-aut-sei=Afify en-aut-mei=Said M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugiharaYuki en-aut-sei=Sugihara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HassanGhmkin en-aut-sei=Hassan en-aut-mei=Ghmkin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZahraMaram H. en-aut-sei=Zahra en-aut-mei=Maram H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SenoAkimasa en-aut-sei=Seno en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AdachiMasaki en-aut-sei=Adachi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Laboratory of Nao‑Biotechnology, Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Division of Biochemistry, Chemistry Department, Faculty of Science, Menoufa University kn-affil= affil-num=3 en-affil=R&D Center, Katayama Chemicals Ind., Co. Ltd, Ina, Minoh kn-affil= affil-num=4 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=R&D Center, Katayama Chemicals Ind., Co. Ltd, Ina, Minoh kn-affil= affil-num=8 en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=15449 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220914 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sodium-glucose cotransporter 2 inhibitors could reduce cardiovascular events in patients with heart failure irrespective of diabetes status. In this prespecified sub-analysis of randomised-controlled trial, we investigated the efficacy of luseogliflozin (2.5 mg daily), a sodium-glucose cotransporter 2 inhibitor, with that of voglibose (0.6 mg daily), an alpha-glucosidase inhibitor, on high-risk lipid profile and inflammatory markers in patients with type-2 diabetes and heart failure. Among the 157 patients studied, there were no significant differences in the mean malondialdehyde LDL or small-dense LDL cholesterol levels between the luseogliflozin and voglibose groups (percent change: 0.2% vs. - 0.6%, p = 0.93; - 1.7% vs. - 8.6%, p= 0.21) after 12 weeks in comparison to levels at the baseline. No significant difference was observed between the two groups in the adiponectin and high-sensitivity C-reactive protein levels after 12 weeks compared to the baseline levels (percent change, - 1.6% vs. - 4.0% and 22.5% vs. 10.0%; p = 0.52 and p = 0.55, respectively). In conclusion, in patients with type-2 diabetes and heart failure, compared to voglibose, luseogliflozin did not significantly improve the high-risk lipoprotein profile including malondialdehyde LDL and small-dense LDL cholesterol or the levels of inflammatory markers, including adiponectin and high-sensitivity C-reactive protein. en-copyright= kn-copyright= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro 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=KiharaHajime en-aut-sei=Kihara en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HataYoshiki en-aut-sei=Hata en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaganoToshihiko en-aut-sei=Nagano en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakaishiAtsushi en-aut-sei=Takaishi en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TodaHironobu en-aut-sei=Toda en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NambaSeiji en-aut-sei=Namba en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraYoichi en-aut-sei=Nakamura en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakuragiSatoru en-aut-sei=Sakuragi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MinagawaTaro en-aut-sei=Minagawa en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KawaiYusuke en-aut-sei=Kawai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=YoshikawaMasaki en-aut-sei=Yoshikawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=The MUSCAT-HF Study Investigators en-aut-sei=The MUSCAT-HF Study Investigators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 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 Internal Medicine, Kihara Cardiovascular Clinic kn-affil= affil-num=4 en-affil=Department of Cardiology, Minamino Cardiovascular Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Iwasa Hospital kn-affil= affil-num=6 en-affil=Department of Cardiology, Mitoyo General Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiology, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Specifed Clinic of Soyokaze Cardiovascular Medicine and Diabetes Care kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Iwakuni Clinical Center kn-affil= affil-num=12 en-affil=Department of Internal Medicine, Minagawa Cardiovascular Clinic kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Okayama City Hospital kn-affil= affil-num=14 en-affil=Department of Internal Medicine, Yoshinaga Hospital kn-affil= affil-num=15 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=16 en-affil=Department of Cardiology, Fukuyama City Hospital kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue= article-no= start-page=108280 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Developing a dataset for the expected anthropogenic mercury release in China in response to the Minamata convention on mercury en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper contains supplementary data in support of a research paper published [1] regarding the expected anthropogenic mercury release in China in response to the Minamata Convention on Mercury (MCM). The dataset provided within this article contains a set of excel spreadsheets. Each spreadsheet contains filtered (collected) and analysed data, i.e., parameters, collected data, calculated and summarized results for mercury distribution by the category of mineral production, intentional uses, secondary metal production, extraction and combustion, and waste treatment in a specific year. The collected (filtered) data in this article consist of the input factor (IF), activity rate data (ARD), output scenario (OS), initial distribution factor (iDF), and redistribution factor (rDF). IF was from the default IF in the United Nations Environment Programme (UNEP) Toolkit Level 2 and published scientific papers. ARD was obtained from the U.S. Geological Survey database, China Statistical Yearbooks, and published scientific papers. The OS content was from the default OS in the UNEP Toolkit Level 2 and published scientific papers. iDF was from the default distribution factor (DF) in the UNEP Toolkit Level 2 and published scientific papers. rDF was from published scientific paper. The mercury input was calculated using IF and ARD. The mercury release to different media in the initial distribution step was calculated using the mercury input and iDF. The release of mercury to the final sinks in the redistribution step was calculated using the amount of sector-specific treatment/disposal, product or by-product, and rDF. The dataset with combination of the collected (filtered) and analyzed data can contribute to an understanding of differences in anthropogenic mercury release before and after implementation of the MCM, especially considering technology transformation in China. Government policymakers involved in hazardous waste management, especially those working on MCM, and engineers and scientists interested in hazardous waste management may benefit from these data. The data can be used for identifying the environmental impact of anthropogenic mercury release before and after the MCM in China. The data can facilitate the creation of strategic management policies for mercury as the MCM is implemented in China. en-copyright= kn-copyright= en-aut-name=Habuer en-aut-sei=Habuer en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTakeshi en-aut-sei=Fujiwara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaokaMasaki en-aut-sei=Takaoka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=Graduate School of Engineering, Kyoto University kn-affil= en-keyword=Anthropogenic activity kn-keyword=Anthropogenic activity en-keyword=Mercury release kn-keyword=Mercury release en-keyword=Minamata convention on mercury kn-keyword=Minamata convention on mercury en-keyword=Technology transformation kn-keyword=Technology transformation END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=14 article-no= start-page=7856 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220716 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Muscle Fiber Composition Changes after Selective Nerve Innervation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Facial nerve paralysis interferes with mimetic muscle function. To reconstruct natural facial movement, free muscle flaps are transplanted as new muscles. However, it is difficult to maintain resting tonus. A dual innervation technique in which other nerves such as the hypoglossal nerve or contralateral facial nerve are added is often applied. Using 10-week-old rats (n = 10), the masseteric and hypoglossal nerves were cut, and the distal stump of the masseteric nerve and the proximal stump of the hypoglossal nerve were then sutured (suture group). In the other group, the masseteric nerve was cut and cauterized (cut group). Immunohistochemistry and microarray were performed on the extracted masseter muscle. The immunohistochemistry results suggested that the muscles in the suture group obtained oxidative characteristics. The microarray showed the genes involved in mitochondrial function, including Perm1. In summary, our data support the validity of the dualinnervation technique for facial paralysis treatment. en-copyright= kn-copyright= en-aut-name=WatanabeShiho en-aut-sei=Watanabe en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OchiaiHiroko en-aut-sei=Ochiai en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakumaHisashi en-aut-sei=Sakuma en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriTaisuke en-aut-sei=Mori en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YazawaMasaki en-aut-sei=Yazawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkaAiko en-aut-sei=Oka en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KishiKazuo en-aut-sei=Kishi en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital, kn-affil= affil-num=2 en-affil=Laboratory of Regenerative Medicine, Department of Plastic and Reconstructive Surgery, Division of Hearing and Balance Disorder, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center kn-affil= affil-num=3 en-affil=Department of Plastic and Reconstructive Surgery, Tokyo Dental College Ichikawa General Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, National Cancer Center Research Institute kn-affil= affil-num=5 en-affil=Department of Plastic and Reconstructive Surgery, Keio University School of Medicine kn-affil= affil-num=6 en-affil=Laboratory of Regenerative Medicine, Department of Plastic and Reconstructive Surgery, Division of Hearing and Balance Disorder, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center kn-affil= affil-num=7 en-affil=Department of Plastic and Reconstructive Surgery, Keio University School of Medicine kn-affil= en-keyword=muscle fiber type kn-keyword=muscle fiber type en-keyword=facial paralysis kn-keyword=facial paralysis en-keyword=dualinnervation kn-keyword=dualinnervation en-keyword=masseter muscle kn-keyword=masseter muscle END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=26021 end-page=26028 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characteristics of Vertical Ga2O3 Schottky Junctions with the Interfacial Hexagonal Boron Nitride Film en-subtitle= kn-subtitle= en-abstract= kn-abstract=We present the device properties of a nickel (Ni)- gallium oxide (Ga2O3) Schottky junction with an interfacial hexagonal boron nitride (hBN) layer. A vertical Schottky junction with the configuration Ni/hBN/Ga2O3/In was created using a chemical vapor-deposited hBN film on a Ga(2)O(3 )substrate. The current-voltage characteristics of the Schottky junction were investigated with and without the hBN interfacial layer. We observed that the turn-on voltage for the forward current of the Schottky junction was significantly enhanced with the hBN interfacial film. Furthermore, the Schottky junction was analyzed under the illumination of deep ultraviolet light (254 nm), obtaining a photoresponsivity of 95.11 mA/W under an applied bias voltage (-7.2 V). The hBN interfacial layer for the Ga2O3-based Schottky junction can serve as a barrier layer to control the turn-on voltage and optimize the device properties for deep-UV photosensor applications. Furthermore, the demonstrated vertical heterojunction with an hBN layer has the potential to be significant for temperature management at the junction interface to develop reliable Ga2O3-based Schottky junction devices. en-copyright= kn-copyright= en-aut-name=RamaVenkata Krishna Rao en-aut-sei=Rama en-aut-mei=Venkata Krishna Rao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RanadeAjinkya K. en-aut-sei=Ranade en-aut-mei=Ajinkya K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DesaiPradeep en-aut-sei=Desai en-aut-mei=Pradeep kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TodankarBhagyashri en-aut-sei=Todankar en-aut-mei=Bhagyashri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KalitaGolap en-aut-sei=Kalita en-aut-mei=Golap kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiHiroo en-aut-sei=Suzuki en-aut-mei=Hiroo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanemuraMasaki en-aut-sei=Tanemura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HayashiYasuhiko en-aut-sei=Hayashi en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Physical Science and Engineering, Nagoya Institute of Technology kn-affil= affil-num=3 en-affil=Department of Physical Science and Engineering, Nagoya Institute of Technology kn-affil= affil-num=4 en-affil=Department of Physical Science and Engineering, Nagoya Institute of Technology kn-affil= affil-num=5 en-affil=Department of Physical Science and Engineering, Nagoya Institute of Technology kn-affil= affil-num=6 en-affil=Graduate School of Natural Science and Technology kn-affil= affil-num=7 en-affil=Department of Physical Science and Engineering, Nagoya Institute of Technology kn-affil= affil-num=8 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=98 cd-vols= no-issue=6 article-no= start-page=227 end-page=282 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective en-subtitle= kn-subtitle= en-abstract= kn-abstract=Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation. en-copyright= kn-copyright= en-aut-name=NAKAMURAEizo en-aut-sei=NAKAMURA en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KOBAYASHIKatsura en-aut-sei=KOBAYASHI en-aut-mei=Katsura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KUNIHIROTak en-aut-sei=KUNIHIRO en-aut-mei=Tak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KITAGAWAHiroshi en-aut-sei=KITAGAWA en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=POTISZILChristian en-aut-sei=POTISZIL en-aut-mei=Christian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OTATsutomu en-aut-sei=OTA en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SAKAGUCHIChie en-aut-sei=SAKAGUCHI en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YAMANAKAMasahiro en-aut-sei=YAMANAKA en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=RATNAYAKEDilan M. en-aut-sei=RATNAYAKE en-aut-mei=Dilan M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TRIPATHIHavishk en-aut-sei=TRIPATHI en-aut-mei=Havishk kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KUMARRahul en-aut-sei=KUMAR en-aut-mei=Rahul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AVRAMESCUMaya-Liliana en-aut-sei=AVRAMESCU en-aut-mei=Maya-Liliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TSUCHIDAHidehisa en-aut-sei=TSUCHIDA en-aut-mei=Hidehisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YACHIYusuke en-aut-sei=YACHI en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MIURAHitoshi en-aut-sei=MIURA en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ABEMasanao en-aut-sei=ABE en-aut-mei=Masanao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=FUKAIRyota en-aut-sei=FUKAI en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FURUYAShizuho en-aut-sei=FURUYA en-aut-mei=Shizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HATAKEDAKentaro en-aut-sei=HATAKEDA en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HAYASHITasuku en-aut-sei=HAYASHI en-aut-mei=Tasuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HITOMIYuya en-aut-sei=HITOMI en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KUMAGAIKazuya en-aut-sei=KUMAGAI en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MIYAZAKIAkiko en-aut-sei=MIYAZAKI en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NAKATOAiko en-aut-sei=NAKATO en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=NISHIMURAMasahiro en-aut-sei=NISHIMURA en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=OKADATatsuaki en-aut-sei=OKADA en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=SOEJIMAHiromichi en-aut-sei=SOEJIMA en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=SUGITASeiji en-aut-sei=SUGITA en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SUZUKIAyako en-aut-sei=SUZUKI en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=USUITomohiro en-aut-sei=USUI en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=YADAToru en-aut-sei=YADA en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=YAMAMOTODaiki en-aut-sei=YAMAMOTO en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=YOGATAKasumi en-aut-sei=YOGATA en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=YOSHITAKEMiwa en-aut-sei=YOSHITAKE en-aut-mei=Miwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=ARAKAWAMasahiko en-aut-sei=ARAKAWA en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=FUJIIAtsushi en-aut-sei=FUJII en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=HAYAKAWAMasahiko en-aut-sei=HAYAKAWA en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=HIRATANaoyuki en-aut-sei=HIRATA en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=HIRATANaru en-aut-sei=HIRATA en-aut-mei=Naru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=HONDARie en-aut-sei=HONDA en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=HONDAChikatoshi en-aut-sei=HONDA en-aut-mei=Chikatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=HOSODASatoshi en-aut-sei=HOSODA en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=IIJIMAYu-ichi en-aut-sei=IIJIMA en-aut-mei=Yu-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=IKEDAHitoshi en-aut-sei=IKEDA en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=ISHIGUROMasateru en-aut-sei=ISHIGURO en-aut-mei=Masateru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=ISHIHARAYoshiaki en-aut-sei=ISHIHARA en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= 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kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=80 ORCID= en-aut-name=YAMADATetsuya en-aut-sei=YAMADA en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=81 ORCID= en-aut-name=YAMAMOTOYukio en-aut-sei=YAMAMOTO en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=82 ORCID= en-aut-name=YANOHajime en-aut-sei=YANO en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=83 ORCID= en-aut-name=YOKOTAYasuhiro en-aut-sei=YOKOTA en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=84 ORCID= en-aut-name=YOSHIHARAKeisuke en-aut-sei=YOSHIHARA en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=85 ORCID= en-aut-name=YOSHIKAWAMakoto en-aut-sei=YOSHIKAWA en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=86 ORCID= en-aut-name=YOSHIKAWAKent en-aut-sei=YOSHIKAWA en-aut-mei=Kent kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=87 ORCID= en-aut-name=FUJIMOTOMasaki en-aut-sei=FUJIMOTO en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=88 ORCID= en-aut-name=WATANABESei-ichiro en-aut-sei=WATANABE en-aut-mei=Sei-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=89 ORCID= en-aut-name=TSUDAYuichi en-aut-sei=TSUDA en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=90 ORCID= affil-num=1 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=4 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=5 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=6 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=7 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=8 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=9 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=10 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=11 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=12 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=13 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=14 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=15 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=16 en-affil=Department of Information and Basic Science, Nagoya City University kn-affil= affil-num=17 en-affil=The Graduate University for Advanced Studies (SOKENDAI) kn-affil= affil-num=18 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=19 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=20 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=21 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=22 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=23 en-affil=Marine Works Japan, Ltd. kn-affil= affil-num=24 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=25 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=26 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=27 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=28 en-affil=Marine Works Japan, Ltd. kn-affil= affil-num=29 en-affil=Graduate School of Science, The University of Tokyo kn-affil= affil-num=30 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=31 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=32 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=33 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=34 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=35 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=36 en-affil=Graduate School of Science, Kobe University kn-affil= affil-num=37 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=38 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=39 en-affil=Graduate School of Science, Kobe University kn-affil= affil-num=40 en-affil=Faculty of Computer Science and Engineering, The University of Aizu kn-affil= affil-num=41 en-affil=Faculty of Science and Technology, Kochi University kn-affil= affil-num=42 en-affil=Faculty of Computer Science and Engineering, The University of Aizu kn-affil= affil-num=43 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=44 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=45 en-affil=Research and Development Directorate, JAXA kn-affil= affil-num=46 en-affil=Department of Physics and Astronomy, Seoul National University kn-affil= affil-num=47 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=48 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=49 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=50 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=51 en-affil=Faculty of Computer Science and Engineering, The University of Aizu kn-affil= affil-num=52 en-affil=National Astronomical Observatory of Japan kn-affil= affil-num=53 en-affil=Observatoire de Paris kn-affil= affil-num=54 en-affil=Faculty of Engineering, Kindai University kn-affil= affil-num=55 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=56 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=57 en-affil=Graduate School of Environmental Studies, Nagoya University kn-affil= affil-num=58 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=59 en-affil=National Astronomical Observatory of Japan kn-affil= affil-num=60 en-affil=National Astronomical Observatory of Japan kn-affil= affil-num=61 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=62 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=63 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=64 en-affil=Graduate School of Science, Kobe University kn-affil= affil-num=65 en-affil=Research and Development Directorate, JAXA kn-affil= affil-num=66 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=67 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=68 en-affil=College of Science, Rikkyo University kn-affil= affil-num=69 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=70 en-affil=Planetary Exploration Research Center (PERC), Chiba Institute of Technology kn-affil= affil-num=71 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=72 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=73 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=74 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=75 en-affil=The Graduate University for Advanced Studies (SOKENDAI) kn-affil= affil-num=76 en-affil=Graduate School of Science, The University of Tokyo kn-affil= affil-num=77 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=78 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=79 en-affil=Planetary Exploration Research Center (PERC), Chiba Institute of Technology kn-affil= affil-num=80 en-affil=Planetary Exploration Research Center (PERC), Chiba Institute of Technology kn-affil= affil-num=81 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=82 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=83 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=84 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=85 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=86 en-affil=The Graduate University for Advanced Studies (SOKENDAI) kn-affil= affil-num=87 en-affil=Research and Development Directorate, JAXA kn-affil= affil-num=88 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= affil-num=89 en-affil=Graduate School of Environmental Studies, Nagoya University kn-affil= affil-num=90 en-affil=Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=6 article-no= start-page=e060621 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Patients' acceptability and implementation outcomes of a case management approach to encourage participation in colorectal cancer screening for people with schizophrenia: a qualitative secondary analysis of a mixed-method randomised clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives We examined the efficacy of case management (CM) interventions to encourage participation in colorectal cancer screening for patients with schizophrenia. This study aimed to clarify patients' acceptability of the intervention and the helpful components of the intervention. Simultaneously, the study aimed to determine the acceptability, appropriateness and feasibility of the intervention from the perspective of psychiatric care providers. Study design and setting This study was a secondary qualitative analysis of a mixed-method randomised controlled trial that evaluated the efficacy of the CM approach to encourage participation in cancer screening for people with schizophrenia. The intervention comprised education and patient navigation for colorectal cancer screening. Interviews were conducted with patients who received the intervention and staff from two psychiatric hospitals in Japan who delivered the intervention. Participants Of the 172 patients with schizophrenia who participated in the trial, 153 were included. In addition, three out of six providers were included. Data collection and analysis Using a structured interview, the case manager asked participants about patient acceptability and the helpful components of the intervention. Content analysis was conducted for the responses obtained, and the number of responses was tabulated by two researchers. For the interviews with the providers, opinions obtained from verbatim transcripts were extracted and summarised. Results Forty-three of the 56 patients perceived that the intervention was acceptable. For the intervention component, inperson counselling with an explanation of the screening process by psychiatric care providers was most frequently reported by the patients as helpful (48 of the 68 respondents). Psychiatric care providers evaluated the intervention as acceptable, appropriate and easy to understand and administer. However, providing the intervention to all patients simultaneously was considered difficult with the current human resources. Conclusions This study showed that the CM intervention was perceived as acceptable by patients and acceptable and appropriate by psychiatric care providers. en-copyright= kn-copyright= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimazuTaichi en-aut-sei=Shimazu en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EtohTsuyoshi en-aut-sei=Etoh en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KodamaMasafumi en-aut-sei=Kodama en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SoRyuhei en-aut-sei=So en-aut-mei=Ryuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsushitaTakanori en-aut-sei=Matsushita en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshimuraYusaku en-aut-sei=Yoshimura en-aut-mei=Yusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HoriiShigeo en-aut-sei=Horii en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujimoriMaiko en-aut-sei=Fujimori en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakahashiHirokazu en-aut-sei=Takahashi en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakayaNaoki en-aut-sei=Nakaya en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiyajiTempei en-aut-sei=Miyaji en-aut-mei=Tempei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HinotsuShiro en-aut-sei=Hinotsu en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HaradaKeita en-aut-sei=Harada en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=UchitomiYosuke en-aut-sei=Uchitomi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamadaNorihito en-aut-sei=Yamada en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=InagakiMasatoshi en-aut-sei=Inagaki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control kn-affil= affil-num=4 en-affil=Department of Nursing, Shimane University Hospital kn-affil= affil-num=5 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=6 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=7 en-affil=Zikei Hospital kn-affil= affil-num=8 en-affil=Zikei Hospital kn-affil= affil-num=9 en-affil=Zikei Hospital kn-affil= affil-num=10 en-affil=Division of Supportive Care, Survivorship and Translational Research, National Cancer Center Institute for Cancer Control kn-affil= affil-num=11 en-affil=Division of Screening Assessment and Management, National Cancer Center Institute for Cancer Control kn-affil= affil-num=12 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=13 en-affil=Department of Clinical Trial Data Management, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Biostatistics and Data Management, Sapporo Medical University kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Group for Supportive Care and Survivorship Research, National Cancer Center Institute for Cancer Control kn-affil= affil-num=18 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=289 cd-vols= no-issue=19 article-no= start-page=5971 end-page=5984 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220517 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Substrate recognition by Arg/Pro‐rich insert domain in calcium/calmodulin‐dependent protein kinase kinase for target protein kinases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Calcium/calmodulin-dependent protein kinase kinases (CaMKKs) activate CaMKI, CaMKIV, protein kinase B/Akt, and AMP-activated protein kinase (AMPK) by phosphorylating Thr residues in activation loops to mediate various Ca2+-signaling pathways. Mammalian cells expressing CaMKK alpha and CaMKK beta lacking Arg/Pro-rich insert domain (RP-domain) sequences showed impaired phosphorylation of AMPK alpha, CaMKI alpha, and CaMKIV, whereas the autophosphorylation activities of CaMKK mutants remained intact and were similar to those of wild-type CaMKKs. Liver kinase B1 (LKB1, an AMPK kinase) complexed with STRAD and MO25 and was unable to phosphorylate CaMKI alpha and CaMKIV; however, mutant LKB1 with the RP-domain sequences of CaMKK alpha and CaMKK beta inserted between kinase subdomains II and III acquired CaMKI alpha and CaMKIV phosphorylating activity in vitro and in transfected cultured cells. Furthermore, ionomycin-induced phosphorylation of hemagglutinin (HA)-CaMKI alpha at Thr177, HA-CaMKIV at Thr196, and HA-AMPK alpha at Thr172 in transfected cells was significantly suppressed by cotransfection of kinase-dead mutants of CaMKK isoforms, but these dominant-negative effects were abrogated with RP-deletion mutants, suggesting that sequestration of substrate kinases by loss-of-function CaMKK mutants requires the RP-domain. This was confirmed by pulldown experiments that showed that dominant-negative mutants of CaMKK alpha and CaMKK beta interact with target kinases but not RP-deletion mutants. Taken together, these results clearly indicate that both CaMKK isoforms require the RP-domain to recognize downstream kinases to interact with and phosphorylate Thr residues in their activation loops. Thus, the RP-domain may be a promising target for specific CaMKK inhibitors. en-copyright= kn-copyright= en-aut-name=KaneshigeRiku en-aut-sei=Kaneshige en-aut-mei=Riku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaYuhei en-aut-sei=Harada en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawamataIssei en-aut-sei=Kawamata en-aut-mei=Issei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KanayamaNaoki en-aut-sei=Kanayama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HatanoNaoya en-aut-sei=Hatano en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakagamiHiroyuki en-aut-sei=Sakagami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=5 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Department of Anatomy, Kitasato University School of Medicine kn-affil= affil-num=9 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=AMP-activated protein kinase kn-keyword=AMP-activated protein kinase en-keyword=Arg/Pro-rich insert domain (RP-domain) kn-keyword=Arg/Pro-rich insert domain (RP-domain) en-keyword=calcium/calmodulin-dependent protein kinase kn-keyword=calcium/calmodulin-dependent protein kinase en-keyword=calcium/calmodulin-dependent protein kinase kinase kn-keyword=calcium/calmodulin-dependent protein kinase kinase en-keyword=substrate recognition kn-keyword=substrate recognition END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=7 article-no= start-page=545 end-page=553 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Conformation-Dependent Reversible Interaction of Ca2+/Calmodulin-Dependent Protein Kinase Kinase with an Inhibitor, TIM-063 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), a Ca2+/CaM-dependent enzyme that phosphorylates and activates multifunctional kinases, including CaMKI, CaMKIV, protein kinase B/Akt, and 5'AMP-activated protein kinase, is involved in various Ca2+-signaling pathways in cells. Recently, we developed an ATP competitive CaMKK inhibitor, TIM-063 (2-hydroxy-3-nitro-7H-benzo-[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one, Ohtsuka et al. Biochemistry 2020, 59, 1701-1710). To gain mechanistic insights into the interaction of CaMKK with TIM-063, we prepared TIM-063-coupled sepharose (TIM-127-sepharose) for association/dissociation analysis of the enzyme/inhibitor complex. CaMKK alpha/beta in transfected COS-7 cells and in mouse brain extracts specifically bound to TIM-127-sepharose and dissociated following the addition of TIM-063 in a manner similar to that of recombinant GST-CaMKK alpha/beta, which could bind to TIM-127sepharose in a Ca2+/CaM-dependent fashion and dissociate from the sepharose following the addition of TIM-063 in a dose dependent manner. In contrast to GST-CaMKK alpha, GST-CaMKK beta was able to weakly bind to TIM-127-sepharose in the presence of EGTA, probably due to the partially active conformation of recombinant GST-CaMKK beta without Ca2+/CaM-binding. These results suggested that the regulatory domain of CaMKK alpha prevented the inhibitor from interacting with the catalytic domain as the GST-CaMKK alpha mutant (residues 126-434) lacking the regulatory domain (residues 438-463) interacted with TIM-127-sepharose regardless of the presence or absence of Ca2+/CaM. Furthermore, CaMKK alpha bound to TIM-127-sepharose in the presence of Ca2+/ CaM completely dissociated from TIM-127-sepharose following the addition of excess EGTA. These results indicated that TIM-063 interacted with and inhibited CaMKK in its active state but not in its autoinhibited state and that this interaction is likely reversible, depending on the concentration of intracellular Ca2+. en-copyright= kn-copyright= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=ΤabuchiYuna en-aut-sei=Τabuchi en-aut-mei=Yuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyagawaTomoyuki en-aut-sei=Miyagawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanayamaNaoki en-aut-sei=Kanayama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=HatanoNaoya en-aut-sei=Hatano en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakagamiHiroyuki en-aut-sei=Sakagami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=IshikawaTeruhiko en-aut-sei=Ishikawa en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=3 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=4 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=5 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Department of Anatomy, Kitasato University School of Medicine kn-affil= affil-num=9 en-affil=Division of Cancer Biology, Institute for Genetic Medicine, Hokkaido University kn-affil= affil-num=10 en-affil=Department of Science Education, Graduate School of Education, Okayama University kn-affil= affil-num=11 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=2 article-no= start-page=195 end-page=202 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Safety and Effectiveness of Perospirone in Comparison to Risperidone for Treatment of Delirium in Patients with Advanced Cancer: A Multicenter Prospective Observational Study in Real-World Psycho-Oncology Settings en-subtitle= kn-subtitle= en-abstract= kn-abstract=The clinical benefit of perospirone for treatment of delirium in patients with advanced cancer is not sufficiently clear. The objective of this study was to compare the safety and effectiveness of perospirone to those of risperidone for the treatment of delirium in patients with advanced cancer. This is a secondary analysis of a multicenter prospective observational study in nine psycho-oncology consultation services in Japan. The study used the Delirium Rating Scale (DRS) Revised-98 to measure effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 to assess safety. Data from 16 patients who received perospirone and 53 patients who received risperidone were analyzed. The mean age was 70 years in the perospirone group and 73 years in the risperidone group. Both groups showed a significant decrease in the total score of DRS-R-98 after three days of treatment (perospirone: 11.7 (7.9-15.4) to 7.0 (3.3-10.7), difference −4.7, effect size=0.72, p=0.003; risperidone: 15.5 (13.6-17.4) to 12.2 (10.1-14.2), difference −3.3, effect size=0.55, p=0.00). The risperidone group showed significant improvements in sleep-wake cycle disturbance, orientation, attention, and visuospatial ability. In the perospirone group, there was a significant improvement of sleep-wake cycle disturbance. The median daily dose of perospirone was 4 mg/day. There were fewer episodes of somnolence as an adverse event in the perospirone group. Low-dose perospirone was thus found to be effective for the treatment of delirium in patients with advanced cancer and may be associated with fewer episodes of over-sedation as an adverse event. en-copyright= kn-copyright= en-aut-name=InoueShinichiro en-aut-sei=Inoue en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaIsseki en-aut-sei=Maeda en-aut-mei=Isseki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OgawaAsao en-aut-sei=Ogawa en-aut-mei=Asao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiuchiKazuhiro en-aut-sei=Yoshiuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=YamadaNorihito en-aut-sei=Yamada en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Palliative Care, Senri-Chuo Hospital kn-affil= affil-num=3 en-affil=Department of Psycho-Oncology Service, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Department of Stress Sciences and Psychosomatic Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=delirium kn-keyword=delirium en-keyword=cancer kn-keyword=cancer en-keyword=perospirone kn-keyword=perospirone en-keyword=risperidone kn-keyword=risperidone END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=2 article-no= start-page=146 end-page=154 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of Scaled-Up Synthetic Method for Retinoid X Receptor Agonist NEt-3IB Contributing to Sustainable Development Goals en-subtitle= kn-subtitle= en-abstract= kn-abstract=Abstract Small-molecular drugs, which are generally inexpensive compared with biopharmaceuticals and can often be taken orally, may contribute to the Sustainable Development Goals (SDGs) adopted by the United Nations. We previously reported the retinoid X receptor (RXR) agonist 4-(ethyl(3-isobutoxy-4-isopropylphenyl)amino)benzoic acid (NEt-3IB, 1) as a small-molecular drug candidate to replace biopharmaceuticals for the treatment of inflammatory bowel disease. The previous synthetic method to 1 required a large amount of organic solvent and extensive purification. In line with the SDGs, we aimed to develop an environmentally friendly, inexpensive method for the large-scale synthesis of 1. The developed method requires only a hydrophobic ether and EtOH as reaction and extraction solvents. The product was purified by recrystallization twice to afford 99% pure 1 at 100 mmol scale in about 30% yield. The optimized process showed a 35-fold improvement of the E-factor (an index of environmental impact) compared to the original method. This work, which changes the solvent used to environmentally preferable ones based on the existing synthetic method for 1, illustrates how synthetic methods for small-molecular drugs can be adapted and improved to contribute to the SDGs. en-copyright= kn-copyright= en-aut-name=TakamuraYuta en-aut-sei=Takamura en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorishitaKen-ichi en-aut-sei=Morishita en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikuzawaShota en-aut-sei=Kikuzawa en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeMasaki en-aut-sei=Watanabe en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakutaHiroki en-aut-sei=Kakuta en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=99 end-page=104 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rapidly Progressive Stenosis of the Left Main Trunk Ostium Starting 21 Months After Stent Implantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rapidly progressive in-stent restenosis (ISR) after stent deployment from the left main trunk (LMT) to the left anterior descending artery (LAD) without plaque at the LMT ostium has not been reported. A 60-year-old Japanese man with a history of scleroderma, pulmonary fibrosis, and type 2 diabetes developed acute myocardial infarction of the right coronary artery (RCA) and was treated by emergency percutaneous coronary intervention (PCI) for RCA. Nine days later he underwent PCI from the LMT to the LAD. Follow-up coronary angiography (CAG) at 9 and 21 months post-PCI did not reveal ISR in any lesion, but the patient experienced cardiac arrest at 25 months post-PCI. Emergency CAG after resuscitation revealed ISR of the LMT ostium; emergency PCI was conducted. The development of ISR at the ostium of the LMT although the patient was free of plaque 4 months before is extremely unusual. This rare ISR of the LMT ostium progressed rapidly after follow-up CAG revealed no ISR at 21 months post-stent implantation. en-copyright= kn-copyright= en-aut-name=NaitoYoichiro en-aut-sei=Naito en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshikawaMasaki en-aut-sei=Yoshikawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KuboMotoki en-aut-sei=Kubo en-aut-mei=Motoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiyamaHiroyasu en-aut-sei=Sugiyama en-aut-mei=Hiroyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiHideyuki en-aut-sei=Suzuki en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujitaShinpei en-aut-sei=Fujita en-aut-mei=Shinpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AraiYasunori en-aut-sei=Arai en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakahashiSho en-aut-sei=Takahashi en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatoYuichi en-aut-sei=Kato en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshidaYu en-aut-sei=Yoshida en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AkaiHiroaki en-aut-sei=Akai en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MurakamiShuhei en-aut-sei=Murakami en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Fukuyama City Hospital kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=left main trunk kn-keyword=left main trunk en-keyword=in-stent restenosis kn-keyword=in-stent restenosis en-keyword=cardiopulmonary arrest kn-keyword=cardiopulmonary arrest END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=17 end-page=24 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Extending Treatment Intervals of R-CHOP Therapy Might Be Acceptable for Some Patients with Non-indolent Non-Hodgkin’s B-cell Lymphoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=R-CHOP therapy is generally performed every 3 weeks. We investigated the effects of extending the interval of R-CHOP therapy for > 1 week on the prognoses of patients with non-indolent non-Hodgkin’s B-cell lymphoma. Among the 338 patients with non-indolent non-Hodgkin’s B-cell lymphoma who received initial chemotherapy at our institution, we focused on 178 patients who received R-CHOP therapy and analyzed the outcomes of the patients stratified by the treatment intervals. The estimated 3-year overall survival (OS) for the entire population was 82.1%. Patients treated at intervals of ≥ 4 weeks were significantly older, and they had significantly longer follow-up periods and lower relative dose intensity. But the estimated 3-year OS was comparable to those treated at <4 weeks (83.3% vs. 80.5% p=0.947). In a multivariate analysis, age and the dose of anti-cancer agents had significant impacts on OS, but there was no significant relationship regarding the treatment intervals. Propensity score matching confirmed the same result. R-CHOP therapy every around 4 weeks could achieve relatively good survival in some selected patients with non-indolent non-Hodgkin’s B-cell lymphoma. en-copyright= kn-copyright= en-aut-name=FujishitaKeigo en-aut-sei=Fujishita en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasuhisaSando en-aut-sei=Yasuhisa en-aut-mei=Sando kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkaSatoshi en-aut-sei=Oka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujisawaYuka en-aut-sei=Fujisawa en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MachidaTakuya en-aut-sei=Machida en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImaiToshi en-aut-sei=Imai en-aut-mei=Toshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= en-keyword=R-CHOP therapy kn-keyword=R-CHOP therapy en-keyword=relative dose intensity kn-keyword=relative dose intensity en-keyword= non-Hodgkin’s lymphoma kn-keyword= non-Hodgkin’s lymphoma END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=7 end-page=15 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Aging-related Characteristics of Subclinical Hypothyroidism Detected in General Practice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Subclinical hypothyroidism (SCH) is diagnosed when serum thyrotropin (TSH) is elevated despite a normal thyroxine level and is known to increase the risk of metabolic disorders. This study was conducted to identify potential laboratory markers suspicious for latent SCH. We retrospectively reviewed 958 outpatients in whom thyroid functions had been examined. Eighty-five (9.1%) of the 939 analyzed subjects had SCH (73% females). In the SCH group, median serum TSH and FT4 levels were 5.04 μU/ml and 1.19 ng/dl, respectively, and auto-thyroid antibodies were detected in 53.8% of patients. SCH group patients were significantly older than patients in the euthyroid group, while there was no intergroup difference in BMI. However, 56.5% of the SCH patients were asymptomatic. In the SCH group, serum aspartate aminotransferase and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher, and the estimated glomerular filtration rate (eGFR) was significantly lower than in the euthyroid group. Among patients less than 65 years of age, SCH patients tended to have lower eGFR and higher LDL-C than euthyroid patients. Age-dependent reductions of red blood cells and serum albumin were more prominent in the SCH than the euthyroid group. Biochemical changes with aging are useful as potential clues for suspecting latent SCH. en-copyright= kn-copyright= en-aut-name=TakamiMasao en-aut-sei=Takami en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoKoichiro en-aut-sei=Yamamoto en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HanayamaYoshihisa en-aut-sei=Hanayama en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=ObikaMikako en-aut-sei=Obika en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=FurukawaMasanori en-aut-sei=Furukawa en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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 Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=aging kn-keyword=aging en-keyword=renal function kn-keyword=renal function en-keyword=cholesterol kn-keyword=cholesterol en-keyword=subclinical hypothyroidism kn-keyword=subclinical hypothyroidism en-keyword=thyroid function kn-keyword=thyroid function END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue= article-no= start-page=694018 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Meclozine Attenuates the MARK Pathway in Mammalian Chondrocytes and Ameliorates FGF2-Induced Bone Hyperossification in Larval Zebrafish en-subtitle= kn-subtitle= en-abstract= kn-abstract=Meclozine has been developed as an inhibitor of fibroblast growth factor receptor 3 (FGFR3) to treat achondroplasia (ACH). Extracellular signal regulated kinase (ERK) phosphorylation was attenuated by meclozine in FGF2-treated chondrocyte cell line, but the site of its action has not been elucidated. Although orally administered meclozine promoted longitudinal bone growth in a mouse model of ACH, its effect on craniofacial bone development during the early stage remains unknown. Herein, RNA-sequencing analysis was performed using murine chondrocytes from FGF2-treated cultured tibiae, which was significantly elongated by meclozine treatment. Gene set enrichment analysis demonstrated that FGF2 significantly increased the enrichment score of mitogen-activated protein kinase (MAPK) family signaling cascades in chondrocytes; however, meclozine reduced this enrichment. Next, we administered meclozine to FGF2-treated larval zebrafish from 8 h post-fertilization (hpf). We observed that FGF2 significantly increased the number of ossified vertebrae in larval zebrafish at 7 days post-fertilization (dpf), while meclozine delayed vertebral ossification in FGF2-induced zebrafish. Meclozine also reversed the FGF2-induced upregulation of ossified craniofacial bone area, including ceratohyal, hyomandibular, and quadrate. The current study provided additional evidence regarding the inhibitory effect of meclozine on the FGF2-induced upregulation of MAPK signaling in chondrocytes and FGF2-induced development of craniofacial and vertebral bones. en-copyright= kn-copyright= en-aut-name=TakemotoGenta en-aut-sei=Takemoto en-aut-mei=Genta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsushitaMasaki en-aut-sei=Matsushita en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkamotoTakaaki en-aut-sei=Okamoto en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItoToshinari en-aut-sei=Ito en-aut-mei=Toshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuuraYuki en-aut-sei=Matsuura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakashimaChieko en-aut-sei=Takashima en-aut-mei=Chieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Chen-YoshikawaToyofumi Fengshi en-aut-sei=Chen-Yoshikawa en-aut-mei=Toyofumi Fengshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EbiHiromichi en-aut-sei=Ebi en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=KitohHiroshi en-aut-sei=Kitoh en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhnoKinji en-aut-sei=Ohno en-aut-mei=Kinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Division of Molecular Therapeutics, Aichi Cancer Center Research Institute kn-affil= affil-num=5 en-affil=Division of Molecular Therapeutics, Aichi Cancer Center Research Institute kn-affil= affil-num=6 en-affil=Division of Molecular Therapeutics, Aichi Cancer Center Research Institute kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Division of Molecular Therapeutics, Aichi Cancer Center Research Institute kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Aichi Children’s Health and Medical Center kn-affil= affil-num=11 en-affil=Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=FGFR3 kn-keyword=FGFR3 en-keyword=achondroplasia kn-keyword=achondroplasia en-keyword=meclozine kn-keyword=meclozine en-keyword=zebrafish kn-keyword=zebrafish en-keyword=bone kn-keyword=bone END start-ver=1.4 cd-journal=joma no-vol=89 cd-vols= no-issue= article-no= start-page=301 end-page=306 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Environmental Impact of Anthropogenic Mercury Release in China en-subtitle= kn-subtitle= en-abstract= kn-abstract=There is increasing public concern regarding the potential risks posed by mercury and mercury compounds. Knowledge of the mercury emission and release inventory, and determination of the main factors that ameliorate the environmental impact of anthropogenic activities, will contribute to environmentally sound mercury management. This study used a life cycle impact assessment to identify the major factors contributing to the overall environmental burden imposed by elemental mercury releases. The environmental impact of the business-as-usual scenario (total impacts = 5.13 GPt) was greater than that of the accelerated technology transformation (ACR) scenario (total impacts = 4.51 GPt), especially in terms of the impact on human health (HH). ACR mainly reduces mercury emissions to air, which affects HH. ompared to its effects on HH, mercury release to the environment has less impact on ecosystem diversity (ED). Mercury release to land had the largest impact on ED, followed by mercury emissions to air and discharge to water. ACR can reduce the harm to HH and marine ecosystems by 12 %. This study provides quantitative information on the environmental impact of mercury release, facilitating strategic management of mercury emissions in line with the Minamata Convention on Mercury (implemented in China in 2017). en-copyright= kn-copyright= en-aut-name=Habuer en-aut-sei=Habuer en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTakeshi en-aut-sei=Fujiwara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaokaMasaki en-aut-sei=Takaoka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=248 cd-vols= no-issue= article-no= start-page=118867 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Layer-specific activation in human primary somatosensory cortex during tactile temporal prediction error processing en-subtitle= kn-subtitle= en-abstract= kn-abstract=The human brain continuously generates predictions of incoming sensory input and calculates corresponding prediction errors from the perceived inputs to update internal predictions. In human primary somatosensory cortex (area 3b), different cortical layers are involved in receiving the sensory input and generation of error signals. It remains unknown, however, how the layers in the human area 3b contribute to the temporal prediction error processing. To investigate prediction error representation in the area 3b across layers, we acquired layer specific functional magnetic resonance imaging (fMRI) data at 7T from human area 3b during a task of index finger poking with no-delay, short-delay and long-delay touching sequences. We demonstrate that all three tasks increased activity in both superficial and deep layers of area 3b compared to the random sensory input. The fMRI signal was differentially modulated solely in the deep layers rather than the superficial layers of area 3b by the delay time. Compared with the no-delay stimuli, activity was greater in the deep layers of area 3b during the short delay stimuli but lower during the long-delay stimuli. This difference activity features in the superficial and deep layers suggest distinct functional contributions of area 3b layers to tactile temporal prediction error processing. The functional segregation in area 3b across layers may reflect that the excitatory and inhibitory interplay in the sensory cortex contributions to flexible communication between cortical layers or between cortical areas. en-copyright= kn-copyright= en-aut-name=YuYinghua en-aut-sei=Yu en-aut-mei=Yinghua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HuberLaurentius en-aut-sei=Huber en-aut-mei=Laurentius kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YangJiajia en-aut-sei=Yang en-aut-mei=Jiajia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukunagaMasaki en-aut-sei=Fukunaga en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChaiYuhui en-aut-sei=Chai en-aut-mei=Yuhui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JangrawDavid C. en-aut-sei=Jangraw en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ChenGang en-aut-sei=Chen en-aut-mei=Gang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HandwerkerDaniel A. en-aut-sei=Handwerker en-aut-mei=Daniel A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MolfesePeter J. en-aut-sei=Molfese en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EjimaYoshimichi en-aut-sei=Ejima en-aut-mei=Yoshimichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SadatoNorihiro en-aut-sei=Sadato en-aut-mei=Norihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WuJinglong en-aut-sei=Wu en-aut-mei=Jinglong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=BandettiniPeter A. en-aut-sei=Bandettini en-aut-mei=Peter A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=MR-Methods Group, MBIC, Cognitive Neuroscience Department, Faculty of Psychology and Neuroscience, University of Maastricht, Cognitive Neuroscience 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=Division of Cerebral Research, National Institute for Physiological Sciences kn-affil= affil-num=5 en-affil=Section on Functional Imaging Methods, National Institute of Mental Health kn-affil= affil-num=6 en-affil=Section on Functional Imaging Methods, National Institute of Mental Health kn-affil= affil-num=7 en-affil=Scientific and Statistical Computational Core, National Institute of Mental Health kn-affil= affil-num=8 en-affil=Section on Functional Imaging Methods, National Institute of Mental Health kn-affil= affil-num=9 en-affil=Section on Functional Imaging Methods, National Institute of Mental Health 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=Division of Cerebral Research, National Institute for Physiological Sciences kn-affil= affil-num=12 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=13 en-affil=Section on Functional Imaging Methods, National Institute of Mental Health kn-affil= en-keyword=Layer-specific fMRI kn-keyword=Layer-specific fMRI en-keyword=Tactile prediction kn-keyword=Tactile prediction en-keyword=Primary somatosensory cortex kn-keyword=Primary somatosensory cortex en-keyword=Temporal prediction error kn-keyword=Temporal prediction error en-keyword=High-resolution CBV-fMRI kn-keyword=High-resolution CBV-fMRI END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue= article-no= start-page=794948 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploring the Retinal Binding Cavity of Archaerhodopsin-3 by Replacing the Retinal Chromophore With a Dimethyl Phenylated Derivative en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rhodopsins act as photoreceptors with their chromophore retinal (vitamin-A aldehyde) and they regulate light-dependent biological functions. Archaerhodopsin-3 (AR3) is an outward proton pump that has been widely utilized as a tool for optogenetics, a method for controlling cellular activity by light. To characterize the retinal binding cavity of AR3, we synthesized a dimethyl phenylated retinal derivative, (2E,4E,6E,8E)-9-(2,6-Dimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenal (DMP-retinal). QM/MM calculations suggested that DMP-retinal can be incorporated into the opsin of AR3 (archaeopsin-3, AO3). Thus, we introduced DMP-retinal into AO3 to obtain the non-natural holoprotein (AO3-DMP) and compared some molecular properties with those of AO3 with the natural A1-retinal (AO3-A1) or AR3. Light-induced pH change measurements revealed that AO3-DMP maintained slow outward proton pumping. Noteworthy, AO3-DMP had several significant changes in its molecular properties compared with AO3-A1 as follows; 1) spectroscopic measurements revealed that the absorption maximum was shifted from 556 to 508 nm and QM/MM calculations showed that the blue-shift was due to the significant increase in the HOMO-LUMO energy gap of the chromophore with the contribution of some residues around the chromophore, 2) time-resolved spectroscopic measurements revealed the photocycling rate was significantly decreased, and 3) kinetical spectroscopic measurements revealed the sensitivity of the chromophore binding Schiff base to attack by hydroxylamine was significantly increased. The QM/MM calculations show that a cavity space is present at the aromatic ring moiety in the AO3-DMP structure whereas it is absent at the corresponding beta-ionone ring moiety in the AO3-A1 structure. We discuss these alterations of the difference in interaction between the natural A1-retinal and the DMP-retinal with binding cavity residues. en-copyright= kn-copyright= en-aut-name=TsuneishiTaichi en-aut-sei=Tsuneishi en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiMasataka en-aut-sei=Takahashi en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujimuraMasaki en-aut-sei=Tsujimura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=IshikitaHiroshi en-aut-sei=Ishikita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakeuchiYasuo en-aut-sei=Takeuchi en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Laboratory of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=4 en-affil=Laboratory of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=6 en-affil=Laboratory of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Laboratory of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=retinal kn-keyword=retinal en-keyword=rhodopsin kn-keyword=rhodopsin en-keyword=proton pump kn-keyword=proton pump en-keyword=derivative kn-keyword=derivative en-keyword=photoreceptor kn-keyword=photoreceptor END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=e72264 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Proton transfer pathway in anion channelrhodopsin-1 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anion channelrhodopsin from Guillardia theta (GtACR1) has Asp234 (3.2 angstrom) and Glu68 (5.3 angstrom) near the protonated Schiff base. Here, we investigate mutant GtACR1s (e.g., E68Q/D234N) expressed in HEK293 cells. The influence of the acidic residues on the absorption wavelengths was also analyzed using a quantum mechanical/molecular mechanical approach. The calculated protonation pattern indicates that Asp234 is deprotonated and Glu68 is protonated in the original crystal structures. The D234E mutation and the E68Q/D234N mutation shorten and lengthen the measured and calculated absorption wavelengths, respectively, which suggests that Asp234 is deprotonated in the wild-type GtACR1. Molecular dynamics simulations show that upon mutation of deprotonated Asp234 to asparagine, deprotonated Glu68 reorients toward the Schiff base and the calculated absorption wavelength remains unchanged. The formation of the proton transfer pathway via Asp234 toward Glu68 and the disconnection of the anion conducting channel are likely a basis of the gating mechanism. en-copyright= kn-copyright= en-aut-name=TsujimuraMasaki en-aut-sei=Tsujimura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawanishiShiho en-aut-sei=Kawanishi en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=IshikitaHiroshi en-aut-sei=Ishikita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, The University of Tokyo 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=Department of Applied Chemistry, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=587 cd-vols= no-issue= article-no= start-page=160 end-page=165 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oligomerization of Ca2+/calmodulin-dependent protein kinase kinase en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ca2+/calmodulin-dependent protein kinase kinases (CaMKKα and β) are regulatory kinases for multiple downstream kinases, including CaMKI, CaMKIV, PKB/Akt, and AMP-activated protein kinase (AMPK) through phosphorylation of each activation-loop Thr residue. In this report, we biochemically characterize the oligomeric structure of CaMKK isoforms through a heterologous expression system using COS-7 cells. Oligomerization of CaMKK isoforms was readily observed by treating CaMKK transfected cells with cell membrane permeable crosslinkers. In addition, His-tagged CaMKKα (His–CaMKKα) pulled down with FLAG-tagged CaMKKα (FLAG–CaMKKα) in transfected cells. The oligomerization of CaMKKα was confirmed by the fact that GST–CaMKKα/His–CaMKKα complex from transiently expressed COS-7 cells extracts was purified to near homogeneity by the sequential chromatography using glutathione-sepharose/Nisepharose and was observed in a Ca2+/CaM-independent manner by reciprocal pulldown assay, suggesting the direct interaction between monomeric CaMKKα. Furthermore, the His-CaMKKα kinase-dead mutant (D293A) complexed with FLAG–CaMKKα exhibited significant CaMKK activity, indicating the active CaMKKα multimeric complex. Collectively, these results suggest that CaMKKα can self-associate in the cells, constituting a catalytically active oligomer that might be important for the efficient activation of CaMKK-mediated intracellular signaling. en-copyright= kn-copyright= en-aut-name=FukumotoYusei en-aut-sei=Fukumoto en-aut-mei=Yusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaradaYuhei en-aut-sei=Harada en-aut-mei=Yuhei 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=KanayamaNaoki en-aut-sei=Kanayama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=HatanoNaoya en-aut-sei=Hatano en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakagamiHiroyuki en-aut-sei=Sakagami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=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=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Anatomy, Kitasato University School of Medicine kn-affil= affil-num=8 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=CaMKK kn-keyword=CaMKK en-keyword=oligomerization kn-keyword=oligomerization en-keyword=Ca2+-signaling kn-keyword=Ca2+-signaling en-keyword=phosphorylation kn-keyword=phosphorylation en-keyword=CaM kinase cascade kn-keyword=CaM kinase cascade END start-ver=1.4 cd-journal=joma no-vol=85 cd-vols= no-issue=11 article-no= start-page=405 end-page=412 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Formation Mechanism of Tempering-Induced Martensite in Ti-10Mo-7Al Alloy kn-title=Ti–10Mo–7Al合金の焼戻し誘起マルテンサイトの形成機構 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The formation mechanism of αAA–martensite (αAAMt) induced by tempering at 450–550℃ for a short time was investigated using Ti–10Mo–7Al alloy. The solution treated and quenched (STQ) sample was composed of β phase and a small amount of αAAMq, and a large amount of αAAMt was generated by rapid tempering at 550℃–3 s using a salt bath. However, αAAMt was completely transformed into a single β phase by aging at 200℃ for 3 min. Reversibility was observed between the αAAMt transformation and the β reverse transformation. In–situ high–temperature X–ray diffraction measurements revealed that αAAMq → β reverse transformation occurred at 200℃ and that a thermally activated αAAiso was generated at 450℃ due to the slow heating rate. In–situ optical microscopic observation of STQ sample with rapid lamp heating revealed that αAAMt was formed during heating process. However, αAAMt did not generate under following conditions; that is, a slow heating rate, thin sample plate, and a small temperature difference until tempering by preheating. On the other hand, rapid tempering using thick plate from liquid nitrogen (−196℃) to 250℃ was performed to ensure a sufficient temperature difference, but αAAMt was not generated at all. From the cross–sectional observation of the STQ plate, it was found that αAAMq was hardly formed on the surface of the sample, but was formed abundantly inside the sample. On the other hand, in the rapidly tempered plate, a large amount of αAAMt was distributed in the surface layer than inside sample. These results suggest that the thermal compressive stress induced by rapid heat treatment contributes to the formation of α''M. en-copyright= kn-copyright= en-aut-name=TakemotoYoshito en-aut-sei=Takemoto en-aut-mei=Yoshito kn-aut-name=竹元嘉利 kn-aut-sei=竹元 kn-aut-mei=嘉利 aut-affil-num=1 ORCID= en-aut-name=YasunoMikiko en-aut-sei=Yasuno en-aut-mei=Mikiko kn-aut-name=安野実希子 kn-aut-sei=安野 kn-aut-mei=実希子 aut-affil-num=2 ORCID= en-aut-name=IkemotoMasaki en-aut-sei=Ikemoto en-aut-mei=Masaki kn-aut-name=池本雅基 kn-aut-sei=池本 kn-aut-mei=雅基 aut-affil-num=3 ORCID= en-aut-name=AndoHiroyuki en-aut-sei=Ando en-aut-mei=Hiroyuki kn-aut-name=安藤寛幸 kn-aut-sei=安藤 kn-aut-mei=寛幸 aut-affil-num=4 ORCID= en-aut-name=ShimizuIchiro en-aut-sei=Shimizu en-aut-mei=Ichiro kn-aut-name=清水一郎 kn-aut-sei=清水 kn-aut-mei=一郎 aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil=岡山大学大学院自然科学研究科 affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil=岡山大学大学院自然科学研究科 affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil=岡山大学大学院自然科学研究科 affil-num=4 en-affil=Faculty of Engineering, Okayama University kn-affil=岡山大学工学部 affil-num=5 en-affil=Faculty of Engineering, Okayama University of Science kn-affil=岡山理科大学工学部 en-keyword=α''–martensite kn-keyword=α''–martensite en-keyword=thermal stress kn-keyword=thermal stress en-keyword=tempering kn-keyword=tempering en-keyword=in situ observation kn-keyword=in situ observation en-keyword=reverse transformation kn-keyword=reverse transformation 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=2021 dt-pub=20210924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=レチノイドX受容体を標的とする非アロステリックアンタゴニストの創製 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WatanabeMasaki en-aut-sei=Watanabe en-aut-mei=Masaki kn-aut-name=渡邉将貴 kn-aut-sei=渡邉 kn-aut-mei=将貴 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211103 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of luseogliflozin on estimated plasma volume in patients with heart failure with preserved ejection fraction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims
Sodium glucose co-transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF).
Methods and results
This study was a post-hoc analysis of the MUSCAT-HF trial (UMIN000018395), a multicentre, prospective, open-label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed-effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group-difference -6.43% [95% confidence interval (CI): -9.11 to -3.74]}, at Week 12 [-8.73% (95%CI: -11.40 to -6.05)], and at Week 24 [-11.02% (95%CI: -13.71 to -8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log-transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019).
Conclusions
Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF. en-copyright= kn-copyright= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=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=KiharaHajime en-aut-sei=Kihara en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HataYoshiki en-aut-sei=Hata en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaganoToshihiko en-aut-sei=Nagano en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakaishiAtsushi en-aut-sei=Takaishi en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TodaHironobu en-aut-sei=Toda en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NanbaSeiji en-aut-sei=Nanba en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraYoichi en-aut-sei=Nakamura en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=SakuragiSatoru en-aut-sei=Sakuragi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MinagawaTaro en-aut-sei=Minagawa en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawaiYusuke en-aut-sei=Kawai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= en-aut-name=YoshikawaMasaki en-aut-sei=Yoshikawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MUSCAT-HF Study Investigators en-aut-sei=MUSCAT-HF Study Investigators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Kihara Cardiovascular Clinic kn-affil= affil-num=5 en-affil=Department of Cardiology, Minamino Cardiovascular Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Iwasa Hospital, kn-affil= affil-num=7 en-affil=Department of Cardiology, Mitoyo General Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiology, Okayama Rosai Hospital kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Specified Clinic of Soyokaze CardioVascular Medicine and Diabetes Care, Matsuyama kn-affil= affil-num=11 en-affil=Department of Internal Medicine, Akaiwa Medical Association Hospital kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Iwakuni Clinical Center kn-affil= affil-num=13 en-affil=Department of Internal Medicine, Minagawa Cardiovascular Clinic kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Okayama City Hospital kn-affil= affil-num=15 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=17 en-affil=Department of Cardiology, Fukuyama City Hospital kn-affil= affil-num=18 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=Estimated plasma volume kn-keyword=Estimated plasma volume en-keyword=Heart failure with preserved ejection fraction kn-keyword=Heart failure with preserved ejection fraction en-keyword=Luseogliflozin kn-keyword=Luseogliflozin en-keyword=Sodium glucose co-transporter 2 inhibitors kn-keyword=Sodium glucose co-transporter 2 inhibitors en-keyword=Voglibose kn-keyword=Voglibose END start-ver=1.4 cd-journal=joma no-vol=83 cd-vols= no-issue= article-no= start-page=7 end-page=12 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anthropogenic Mercury Release Flow in China en-subtitle= kn-subtitle= en-abstract= kn-abstract=China is the largest emitter of anthropogenic mercury worldwide. Implementation of the Minamata Convention on Mercury will significantly impact the development, use, and management of mercury resources. Chinese mercury management policies require significant adjustment. There is an urgent need to develop a current national mercury inventory to estimate mercury inputs and outputs by source category, and to clarify the distributions to various environmental scenarios. Here, the mercury releases are quantitatively analysed to facilitate the implementation of strategic mercury management policies in China. First, the mercury inputs and outputs by source categories in 2016 are quantified and then the mercury distributions to various environmental and intermediate sinks are estimated. The total mercury input was 5,116 t in 2016, of which 77% was attributable to mineral production. In total, 3,083 t were released into various environmental and intermediate reservoirs. Of this total, 53.8 % was intentional uses, followed by extraction and combustion (26.5%), and mineral production (19.6 %); 1,501 t were released into air, water, and land, of which extraction and combustion accounted for 48.6 % followed by mineral production (25.7 %) and intentional uses (25.6 %). en-copyright= kn-copyright= en-aut-name=Habuer en-aut-sei=Habuer en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTakeshi en-aut-sei=Fujiwara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaokaMasaki en-aut-sei=Takaoka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Okayama University kn-affil= affil-num=2 en-affil=Okayama University kn-affil= affil-num=3 en-affil=Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=2 article-no= start-page=143 end-page=151 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Future trends of excess mercury in Asia in response to Minamata Convention on Mercury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Owing to rapid industrialization, Asia has become the main source of mercury emissions and a significant net importer of mercury.
Therefore, the situation regarding excess mercury in Asia needs to be better understood. In this study, mercury flows and excess mercury in 2010–2050 in Asian regions, with a particular focus on China, are assessed under updated assumptions. The excess mercury in China in 2030 and 2050 is estimated to be 125 and 284 tons, respectively. The cumulative excess mercury in China will reach around 10,000 tons in 2050 under the assumption of no export of it in the years 2010–2050. In addition, the year in which mercury reaches a surplus in Asia (excl. China) is estimated to be 2039. The mercury supply in Asia strongly depends on the usage of excess mercury in China. It is estimated that mercury supplies will be insufficient in Asia until at least 2017. These predictions should support decision-making and planning for long-term storage capacity, discussions of regional coordination, securing of technical support, and development of the basic design of related facilities. en-copyright= kn-copyright= en-aut-name=Habuer en-aut-sei=Habuer en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamaguchiDaisuke en-aut-sei=Hamaguchi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhouYingjun en-aut-sei=Zhou en-aut-mei=Yingjun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujimoriTakashi en-aut-sei=Fujimori en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakaokaMasaki en-aut-sei=Takaoka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Engineering, Kyoto University kn-affil= affil-num=3 en-affil=Graduate School of Engineering, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Engineering, Kyoto University kn-affil= affil-num=5 en-affil=Graduate School of Engineering, Kyoto University kn-affil= en-keyword=Excess mercury kn-keyword=Excess mercury en-keyword=Long-term strategy kn-keyword=Long-term strategy en-keyword=Scenario analysis kn-keyword=Scenario analysis en-keyword=China kn-keyword=China en-keyword=Asia kn-keyword=Asia END start-ver=1.4 cd-journal=joma no-vol=323 cd-vols= no-issue= article-no= start-page=129089 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The response of anthropogenic mercury release in China to the Minamata Convention on Mercury: A hypothetical expectation en-subtitle= kn-subtitle= en-abstract= kn-abstract=The combination of anthropogenic activities and long-term atmospheric transport has resulted in a sustained increase in global mercury concentrations in air, in water and on land. The Minamata Convention on Mercury (MCM), is a global treaty with the goal of protecting human health and the environment from anthropogenic releases of mercury. This study aimed to quantify the mercury inputs and outputs in China in 2016–2019 according to five source categories and investigate the effect of an accelerated scenario/technology transformation required by the MCM on the subsequent distribution of mercury among environmental and intermediate reservoirs. Mercury releases to natural environment decreased dramatically after the MCM, such that around 840 t of mercury was released to those reservoirs in 2019, which is less than 21% of that in 2016 (1,063 t) when an accelerated scenario/technology transformation (STranf) was taken into consideration. Applying the accelerated STranf can hardly change the total release amount to the natural environment, also can reduce 53 t and 58 t of atmospheric emission in 2018 and 2019 respectively. Atmospheric emission was most sensitive to STranf, followed by emissions to land and water. This is the first attempt to provide a systematic evaluation of the effectiveness of the MCM based on the hypothetical expectations. As the MCM moves into the implementation phase, further information from scientific data and studies is critically needed to support decision-making and management. The results of this study can provide such information, facilitating the creation of strategic management policies for mercury as the MCM is implemented in China. en-copyright= kn-copyright= en-aut-name=Habuer en-aut-sei=Habuer en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTakeshi en-aut-sei=Fujiwara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaokaMasaki en-aut-sei=Takaoka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=Graduate School of Engineering, Kyoto University kn-affil= en-keyword=Mercury kn-keyword=Mercury en-keyword=Anthropogenic release kn-keyword=Anthropogenic release en-keyword=Distribution flow kn-keyword=Distribution flow en-keyword=Substance flow analysis kn-keyword=Substance flow analysis en-keyword=Minamata Convention on Mercury kn-keyword=Minamata Convention on Mercury en-keyword=China kn-keyword=China END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=6 article-no= start-page=691 end-page=697 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Status of Acute Stroke Practice in Patients with a Cardiac Implantable Electronic Device en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although diagnostic and therapeutic strategies for acute stroke patients in Japan depend largely on magnetic resonance imaging (MRI), patients with cardiac implantable electronic devices (CIED) must still rely on com-puted tomography (CT). We retrospectively analyzed clinical and neuroimaging data of ischemic stroke patients with CIED treated at our hospital. Forty-five patients were enrolled in the study. Patients were divided into two groups according to whether corresponding lesions were detected (group A, n = 21) or not detected (group B, n = 24) by the first brain CT. We also evaluated in detail the clinical courses of patients who arrived at hospital within therapeutic time windows for recanalization therapy. Negative fresh infarct in the first CT was associated, though not significantly, with early onset-to-arrival time and subcortical white matter infarction. Five patients did not undergo recanalization therapy because their families did not agree to the procedure. The reasons for their lack of consent included inadequate information about the safety and efficacy of recanalization therapy because MRI could not be performed. Our study confirmed delayed detection of the corresponding lesion and undertreatment for acute stroke in patients with CIED. en-copyright= kn-copyright= en-aut-name=KatoYuji en-aut-sei=Kato en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiTakeshi en-aut-sei=Hayashi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatoRitsushi en-aut-sei=Kato en-aut-mei=Ritsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchinoAkira en-aut-sei=Uchino en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TakahashiShinichi en-aut-sei=Takahashi en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Neurology and Cerebrovascular Medicine, Saitama Medical University International Medical Center kn-affil= affil-num=2 en-affil=Department of Neurology and Cerebrovascular Medicine, Saitama Medical University International Medical Center kn-affil= affil-num=3 en-affil=Department of Cardiology, Saitama Medical University International Medical Center kn-affil= affil-num=4 en-affil=Department of Diagnostic Radiology,Saitama Medical University International Medical Center kn-affil= affil-num=5 en-affil=Department of Neurology and Cerebrovascular Medicine, Saitama Medical University International Medical Center kn-affil= affil-num=6 en-affil=Department of Neurology and Cerebrovascular Medicine, Saitama Medical University International Medical Center kn-affil= en-keyword=stroke kn-keyword=stroke en-keyword=cardiac implantable electronic device kn-keyword=cardiac implantable electronic device en-keyword=computed tomography kn-keyword=computed tomography en-keyword=magnetic resonance imaging kn-keyword=magnetic resonance imaging END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=10 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210829 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Regulation of germination by targeted mutagenesis of grain dormancy genes in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=High humidity during harvest season often causes pre-harvest sprouting in barley (Hordeum vulgare). Prolonged grain dormancy prevents pre-harvest sprouting; however, extended dormancy can interfere with malt production and uniform germination upon sowing. In this study, we used Cas9-induced targeted mutagenesis to create single and double mutants in QTL FOR SEED DORMANCY 1 (Qsd1) and Qsd2 in the same genetic background. We performed germination assays in independent qsd1 and qsd2 single mutants, as well as in two double mutants, which revealed a strong repression of germination in the mutants. These results demonstrated that normal early grain germination requires both Qsd1 and Qsd2 function. However, germination of qsd1 was promoted by treatment with 3% hydrogen peroxide, supporting the notion that the mutants exhibit delayed germination. Likewise, exposure to cold temperatures largely alleviated the block of germination in the single and double mutants. Notably, qsd1 mutants partially suppress the long dormancy phenotype of qsd2, while qsd2 mutant grains failed to germinate in the light, but not in the dark. Consistent with the delay in germination, abscisic acid accumulated in all mutants relative to the wild type, but abscisic acid levels cannot maintain long-term dormancy and only delay germination. Elucidation of mutant allele interactions, such as those shown in this study, are important for fine-tuning traits that will lead to the design of grain dormancy through combinations of mutant alleles. Thus, these mutants will provide the necessary germplasm to study grain dormancy and germination in barley. en-copyright= kn-copyright= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HoffieRobert E. en-aut-sei=Hoffie en-aut-mei=Robert E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AbeFumitaka en-aut-sei=Abe en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MunemoriHiromi en-aut-sei=Munemori en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=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=EndoMasaki en-aut-sei=Endo en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MikamiMasafumi en-aut-sei=Mikami en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraShingo en-aut-sei=Nakamura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KumlehnJochen en-aut-sei=Kumlehn en-aut-mei=Jochen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben kn-affil= affil-num=3 en-affil=Institute of Crop Science, NARO 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 Agrobiological Sciences, NARO kn-affil= affil-num=7 en-affil=Institute of Agrobiological Sciences, NARO kn-affil= affil-num=8 en-affil=Institute of Crop Science, NARO kn-affil= affil-num=9 en-affil=Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Hordeum vulgare kn-keyword=Hordeum vulgare en-keyword=seed dormancy kn-keyword=seed dormancy en-keyword=targeted genome modification kn-keyword=targeted genome modification en-keyword=CRISPR kn-keyword=CRISPR en-keyword=Cas9 nuclease kn-keyword=Cas9 nuclease en-keyword=pre-harvest sprouting kn-keyword=pre-harvest sprouting END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=715752 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Retinoid X Receptor Agonist Directed to the Large Intestine Ameliorates T-Cell-Mediated Colitis in Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Retinoid X receptor (RXR) is a nuclear receptor that heterodimerizes with several nuclear receptors, integrating ligand-mediated signals across the heterodimers. Synthetic RXR agonists have been developed to cure certain inflammatory diseases, including inflammatory bowel diseases (IBDs). However, pre-existing RXR agonists, which are lipophilic and readily absorbed in the upper intestine, cause considerable adverse effects such as hepatomegaly, hyperlipidemia, and hypothyroidism. To minimize these adverse effects, we have developed an RXR agonist, NEt-3IB, which has lipophilic and thus poorly absorptive properties. In this study, we evaluated the effects of NEt-3IB in an experimental murine colitis model induced through the adoptive transfer of CD45RB(high)CD4(+) T cells. Pharmacokinetic studies demonstrated that the major portion of NEt-3IB was successfully delivered to the large intestine after oral administration. Notably, NEt-3IB treatment suppressed the development of T cell-mediated chronic colitis, as indicated by improvement of wasting symptoms, inflammatory infiltration, and mucosal hyperplasia. The protective effect of NEt-3IB was mediated by the suppression of IFN-gamma-producing Th1 cell expansion in the colon. In conclusion, NEt-3IB, a large intestine-directed RXR agonist, is a promising drug candidate for IBDs. en-copyright= kn-copyright= en-aut-name=MatsumotoRyohtaroh en-aut-sei=Matsumoto en-aut-mei=Ryohtaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiDaisuke en-aut-sei=Takahashi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeMasaki en-aut-sei=Watanabe en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakataniShunsuke en-aut-sei=Nakatani en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakamuraYuta en-aut-sei=Takamura en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurosakiYuji en-aut-sei=Kurosaki en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KakutaHiroki en-aut-sei=Kakuta en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaseKoji en-aut-sei=Hase en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Biochemistry, Graduate School of Pharmaceutical Science and Faculty of Pharmacy, Keio University kn-affil= affil-num=2 en-affil=Division of Biochemistry, Graduate School of Pharmaceutical Science and Faculty of Pharmacy, Keio University kn-affil= affil-num=3 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Biochemistry, Graduate School of Pharmaceutical Science and Faculty of Pharmacy, Keio University kn-affil= en-keyword=RXR kn-keyword=RXR en-keyword=NEt-3IB kn-keyword=NEt-3IB en-keyword=inflammatory bowel disease kn-keyword=inflammatory bowel disease en-keyword=colitis kn-keyword=colitis en-keyword=Th1 cells kn-keyword=Th1 cells END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=7 article-no= start-page=e046505 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study protocol for endoscopic ultrasonography-guided ethanol injection therapy for patients with pancreatic neuroendocrine neoplasm: a multicentre prospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction The management of small pancreatic neuroendocrine neoplasms (PNENs) remains controversial. The standard treatment for PNENs is surgical resection; however, invasiveness of surgical procedure remains higher and the incidence of postoperative adverse events is still high. Recently, the efficacy and safety of endoscopic ultrasonography (EUS)-guided ethanol injection for small PNENs has been preliminarily demonstrated. Thus, a multicentre prospective study is being conducted to evaluate the efficacy and safety of EUS-guided ethanol injection therapy for small PNENs. Methods and analysis The major eligibility criteria are the presence of pathologically diagnosed grade (G) 1 tumour, a tumour size of <= 15 mm and non-functional PNEN or insulinoma. For treatment, we will use a 25-gauge needle and pure ethanol. Contrast-enhanced CT (CE-CT) will be performed on postoperative day 3-5, and if enhanced areas of the tumour are still apparent, an additional session is scheduled during the same hospitalisation period. We set the total amount of ethanol per session to 2 mL. To evaluate the efficacy and safety, CE-CT will be performed at 1 and 6 months after treatment. The primary endpoint is the percentage of subjects who achieved all of the following evaluated points. Efficacy will be evaluated based on the achievement of complete ablation (defined as no enhanced area within the tumour on CE-CT) at 1 and 6 months. Safety will be evaluated based on the avoidance of severe adverse events within 1 month after treatment, continuing severe pancreatic fistula at 1 month after treatment and the incidence and/or exacerbation of diabetes mellitus at 6 months after treatment. Ethics and dissemination This protocol has been approved by Okayama University Certified Review Board (approval number. CRB19-007). The results will be submitted to peer-reviewed journals and will be presented at international conferences. en-copyright= kn-copyright= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitanoMasayuki en-aut-sei=Kitano en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaraKazuo en-aut-sei=Hara en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuwataniMasaki en-aut-sei=Kuwatani en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AshidaReiko en-aut-sei=Ashida en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakenakaMamoru en-aut-sei=Takenaka en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamazakiTatsuhiro en-aut-sei=Yamazaki en-aut-mei=Tatsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakuraiJun en-aut-sei=Sakurai en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshidaMichihiro en-aut-sei=Yoshida en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=Second Department of Internal Medicine, Wakayama Medical University kn-affil= affil-num=4 en-affil=Gastroenterology, Aichi Cancer Center kn-affil= affil-num=5 en-affil=Gastroenterology and Hepatology, Hokkaido University Hospital kn-affil= affil-num=6 en-affil=Second Department of Internal Medicine, Wakayama Medical University kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kindai University kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=gastroenterology kn-keyword=gastroenterology en-keyword=endoscopy kn-keyword=endoscopy en-keyword=pancreatic disease kn-keyword=pancreatic disease END start-ver=1.4 cd-journal=joma no-vol=57 cd-vols= no-issue=8 article-no= start-page=846 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Patient Clinical Variables in Osteoporosis Classification Using Hip X-rays in Deep Learning Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Objectives: A few deep learning studies have reported that combining image features with patient variables enhanced identification accuracy compared with image-only models. However, previous studies have not statistically reported the additional effect of patient variables on the image-only models. This study aimed to statistically evaluate the osteoporosis identification ability of deep learning by combining hip radiographs with patient variables. Materials andMethods: We collected a dataset containing 1699 images from patients who underwent skeletal-bone-mineral density measurements and hip radiography at a general hospital from 2014 to 2021. Osteoporosis was assessed from hip radiographs using convolutional neural network (CNN) models (ResNet18, 34, 50, 101, and 152). We also investigated ensemble models with patient clinical variables added to each CNN. Accuracy, precision, recall, specificity, F1 score, and area under the curve (AUC) were calculated as performance metrics. Furthermore, we statistically compared the accuracy of the image-only model with that of an ensemble model that included images plus patient factors, including effect size for each performance metric. Results: All metrics were improved in the ResNet34 ensemble model compared with the image-only model. The AUC score in the ensemble model was significantly improved compared with the image-only model (difference 0.004; 95% CI 0.002-0.0007; p = 0.0004, effect size: 0.871). Conclusions: This study revealed the additional effect of patient variables in identification of osteoporosis using deep CNNs with hip radiographs. Our results provided evidence that the patient variables had additive synergistic effects on the image in osteoporosis identification. en-copyright= kn-copyright= en-aut-name=YamamotoNorio en-aut-sei=Yamamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaKazutaka en-aut-sei=Yamashita en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ManabeMasaki en-aut-sei=Manabe en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawasakiKeisuke en-aut-sei=Kawasaki en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FurukiYoshihiko en-aut-sei=Furuki en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=4 en-affil=Department of Radiation Technology, Kagawa Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=12 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=patient variables kn-keyword=patient variables en-keyword=osteoporosis kn-keyword=osteoporosis en-keyword=deep learning kn-keyword=deep learning en-keyword=convolutional neural network kn-keyword=convolutional neural network en-keyword=ensemble model kn-keyword=ensemble model en-keyword=effect size kn-keyword=effect size END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=8 article-no= start-page=1078 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210822 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Factors Affecting Participation in Leisure Activities in Patients after Breast Cancer Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The purpose of this study was to investigate the factors related to patient's participation in leisure activity in breast cancer patients with axillary lymph node dissection at 3 months after surgery. Methods: In total, 160 women who were employed before their surgery were evaluated. Age, body mass index (BMI), employment, level of lymph node dissection, marital status, children, coresident household members, preoperative chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, shoulder range of motion test, upper limb function, quality of life, and patient's participation in leisure activity were evaluated. Results: Patients who undertook leisure activities constituted the leisure activity group, and patients who did not constituted the non-leisure activity group. Global health status, emotional function, social function, and dyspnea were significantly different between the leisure activity group and the non-leisure activity group at 3 months after surgery (p < 0.05). Regarding factors that affected participation in leisure activities, logistic regression analysis showed that only participation in leisure activities before surgery was significantly associated with participation in leisure activities at 3 months after surgery (p < 0.05). Conclusion: Patients who did not participate in leisure activities prior to surgery were unlikely to participate 3 months after surgery and thus require intervention to encourage their involvement. en-copyright= kn-copyright= en-aut-name=AkezakiYoshiteru en-aut-sei=Akezaki en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikuuchiMasato en-aut-sei=Kikuuchi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TominagaRitsuko en-aut-sei=Tominaga en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurokawaHideaki en-aut-sei=Kurokawa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoMasaki en-aut-sei=Okamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamadaMakiko en-aut-sei=Hamada en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=OhsumiShozo en-aut-sei=Ohsumi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugiharaShinsuke en-aut-sei=Sugihara en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Physical Therapy, Kochi Professional University of Rehabilitation kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Rehabilitation Medicine, Higashi Tokushima Medical Center kn-affil= affil-num=8 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=10 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=leisure kn-keyword=leisure en-keyword=surgery kn-keyword=surgery en-keyword=rehabilitation kn-keyword=rehabilitation en-keyword=factor kn-keyword=factor END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=16 article-no= start-page=e020103 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210817 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predictive Value of the Cardio-Ankle Vascular Index for Cardiovascular Events in Patients at Cardiovascular Risk en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND: Arterial stiffness is an important predictor of cardiovascular events; however, indexes for measuring arterial stiffness have not been widely incorporated into routine clinical practice. This study aimed to determine whether the cardio-ankle vascular index (CAVI), based on the blood pressure-independent stiffness parameter beta and reflecting arterial stiffness from the origin of the ascending aorta, is a good predictor of cardiovascular events in patients with cardiovascular disease risk factors in a large prospective cohort.

METHODS AND RESULTS: This multicenter prospective cohort study, commencing in May 2013, with a 5-year follow-up period, included patients (aged 40-74 years) with cardiovascular disease risks. The primary outcome was the composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Among 2932 included patients, 2001 (68.3%) were men; the mean (SD) age at diagnosis was 63 (8) years. During the median follow-up of 4.9 years, 82 participants experienced primary outcomes. The CAVI predicted the primary outcome (hazard ratio, 1.38; 95% CI, 1.16-1.65; P<0.001). In terms of event subtypes, the CAVI was associated with cardiovascular death and stroke but not with myocardial infarction. When the CAVI was incorporated into a model with known cardiovascular disease risks for predicting cardiovascular events, the global chi(2) value increased from 33.8 to 45.2 (P<0.001), and the net reclassification index was 0.254 (P=0.024).

CONCLUSIONS: This large cohort study demonstrated that the CAVI predicted cardiovascular events. en-copyright= kn-copyright= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiraiKohji en-aut-sei=Shirai en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HorinakaShigeo en-aut-sei=Horinaka en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HigakiJitsuo en-aut-sei=Higaki en-aut-mei=Jitsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamuraShigeo en-aut-sei=Yamamura en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaikiAtsuhito en-aut-sei=Saiki en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakahashiMao en-aut-sei=Takahashi en-aut-mei=Mao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MasakiMitsuru en-aut-sei=Masaki en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkuraTakafumi en-aut-sei=Okura en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KotaniKazuhiko en-aut-sei=Kotani en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KubozonoTakuro en-aut-sei=Kubozono en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=KiharaHajime en-aut-sei=Kihara en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HasegawaKoji en-aut-sei=Hasegawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Satoh-AsaharaNoriko en-aut-sei=Satoh-Asahara en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OrimoHajime en-aut-sei=Orimo en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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 Internal Medicine, Mihama Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Dokkyo Medical University kn-affil= affil-num=5 en-affil=Department of Cardiology, South Matsuyama Hospital kn-affil= affil-num=6 en-affil=Faculty of Pharmaceutical Sciences, Josai International University kn-affil= affil-num=7 en-affil=Center of Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center, Sakura-City kn-affil= affil-num=8 en-affil=Division of Cardiovascular Medicine (Sakura), Department of Internal Medicine, Faculty of Medicine, Toho University kn-affil= affil-num=9 en-affil=Division of Clinical Laboratory Medicine, Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine kn-affil= affil-num=10 en-affil=Department of Cardiology, Yawatahama City General Hospital kn-affil= affil-num=11 en-affil=Division of Community and Family Medicine, Jichi Medical University kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, The Sakakibara Heart Institute of Okayama kn-affil= affil-num=14 en-affil=Department of Internal Medicine, Kihara Cardiovascular Clinic kn-affil= affil-num=15 en-affil=Division of Translational Research kn-affil= affil-num=16 en-affil=Department of Endocrinology, Metabolism, and Hypertension Research kn-affil= affil-num=17 en-affil=Clinical Research Institute, National Hospital Organization Kyoto Medical Center kn-affil= en-keyword=arterial stiffness kn-keyword=arterial stiffness en-keyword=blood pressure kn-keyword=blood pressure en-keyword=cardiovascular events kn-keyword=cardiovascular events en-keyword=pulse-wave velocity kn-keyword=pulse-wave velocity en-keyword=risk factor kn-keyword=risk factor END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue= article-no= start-page=102404 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Regulation of the tubulin polymerization-promoting protein by Ca2+/S100 proteins en-subtitle= kn-subtitle= en-abstract= kn-abstract=To elucidate S100 protein-mediated signaling pathways, we attempted to identify novel binding partners for S100A2 by screening protein arrays carrying 19,676 recombinant glutathione S-transferase (GST)-fused human proteins with biotinylated S100A2. Among newly discovered putative S100A2 interactants, including TMLHE, TRH, RPL36, MRPS34, CDR2L, OIP5, and MED29, we identified and characterized the tubulin polymerization-promoting protein (TPPP) as a novel S100A2-binding protein. We confirmed the interaction of TPPP with Ca2+/S100A2 by multiple independent methods, including the protein array method, S100A2 overlay, and pulldown assay in vitro and in transfected COS-7 cells. Based on the results from the S100A2 overlay assay using various GST-TPPP mutants, the S100A2-binding region was identified in the C-terminal (residues 111-160) of the central core domain of a monomeric form of TPPP that is involved in TPPP dimerization. Chemical cross-linking experiments indicated that S100A2 suppresses dimer formation of His-tagged TPPP in a dosedependent and a Ca2+-dependent manner. In addition to S100A2, TPPP dimerization is disrupted by other multiple S100 proteins, including S100A6 and S100B, in a Ca2+-dependent manner but not by S100A4. This is consistent with the fact that S100A6 and S100B, but not S100A4, are capable of interacting with GST-TPPP in the presence of Ca2+. Considering these results together, TPPP was identified as a novel target for S100A2, and it is a potential binding target for other multiple S100 proteins, including S100A6 and S100B. Direct binding of the S100 proteins with TPPP may cause disassembly of TPPP dimer formation in response to the increasing concentration of intracellular Ca2+, thus resulting in the regulation of the physiological function of TPPP, such as microtubule organization. en-copyright= kn-copyright= en-aut-name=DoiSeita en-aut-sei=Doi en-aut-mei=Seita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiokaNaoki en-aut-sei=Fujioka en-aut-mei=Naoki 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=KondoRina en-aut-sei=Kondo en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoMaho en-aut-sei=Yamamoto en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DendaMiwako en-aut-sei=Denda en-aut-mei=Miwako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KanayamaNaoki en-aut-sei=Kanayama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HatanoNaoya en-aut-sei=Hatano en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorishitaRyo en-aut-sei=Morishita en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HasegawaTakafumi en-aut-sei=Hasegawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=CellFree Sciences Co., Ltd kn-affil= affil-num=7 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=CellFree Sciences Co., Ltd kn-affil= affil-num=11 en-affil=Division of Neurology, Department of Neuroscience and Sensory Organs, Tohoku University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=11086 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn's disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD. en-copyright= kn-copyright= en-aut-name=YasutomiEriko en-aut-sei=Yasutomi en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakeiKensuke en-aut-sei=Takei en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=YamamotoShumpei en-aut-sei=Yamamoto en-aut-mei=Shumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhmoriMasayasu en-aut-sei=Ohmori en-aut-mei=Masayasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkaShohei en-aut-sei=Oka en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HaradaKeita en-aut-sei=Harada en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FurukawaMasaki en-aut-sei=Furukawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ItoshimaKouichi en-aut-sei=Itoshima en-aut-mei=Kouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OkadaKen en-aut-sei=Okada en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 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=17 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=18 ORCID= en-aut-name=KatoJun en-aut-sei=Kato en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Laboratory Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterology, Graduate School of Medicine, Chiba University kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=385 end-page=389 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful Surgical Management of Acute Appendicitis in a Centenarian en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OkitaAtsushi en-aut-sei=Okita en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujimuraMasaki en-aut-sei=Fujimura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoIsao en-aut-sei=Sato en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChinoYoshihide en-aut-sei=Chino en-aut-mei=Yoshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YubaTakafumi en-aut-sei=Yuba en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MizutaniMakoto en-aut-sei=Mizutani en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TabataTomotake en-aut-sei=Tabata en-aut-mei=Tomotake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IidaMinoru en-aut-sei=Iida en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KumanoKimitsuka en-aut-sei=Kumano en-aut-mei=Kimitsuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Endoscopic Surgery Center, Daiichi Towakai Hospital kn-affil= affil-num=2 en-affil=Endoscopic Surgery Center, Daiichi Towakai Hospital kn-affil= affil-num=3 en-affil=Endoscopic Surgery Center, Daiichi Towakai Hospital kn-affil= affil-num=4 en-affil=Endoscopic Surgery Center, Daiichi Towakai Hospital kn-affil= affil-num=5 en-affil=Endoscopic Surgery Center, Daiichi Towakai Hospital kn-affil= affil-num=6 en-affil=Endoscopic Surgery Center, Daiichi Towakai Hospital kn-affil= affil-num=7 en-affil=Endoscopic Surgery Center, Daiichi Towakai Hospital kn-affil= affil-num=8 en-affil=Endoscopic Surgery Center, Daiichi Towakai Hospital kn-affil= affil-num=9 en-affil=Endoscopic Surgery Center, Daiichi Towakai Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=335 end-page=343 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Baseline Neutrophil-to-Lymphocyte Ratio and Glasgow Prognostic Score are Associated with Clinical Outcome in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Treated with Nivolumab en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recurrent or metastatic head and neck squamous cell carcinoma (R/MHNSCC) has a poor prognosis. Although nivolumab is approved in Japan for treating R/MHNSCC, the response rate is low. Therefore, identifying pretreatment prognostic factors is necessary. This study assessed the utility of the neutrophil-to-lymphocyte ratio (NLR) and Glasgow Prognostic Score (GPS) as biomarkers of response to nivolumab. We retrospectively collected the data of 56 R/MHNSCC patients treated with nivolumab between May 2017 and December 2019. The Kaplan–Meier method and log-rank test were used to estimate overall survival (OS) and progression-free survival (PFS), and multivariate Cox hazard regression analysis was used to identify independent predictors of survival. Patients with a low pretreatment NLR had prolonged OS, and patients with a low pretreatment GPS had increased OS and PFS. A performance score (PS) of 0-1, development of immune-related adverse events, and GPS of 0-1 were significantly associated with OS in multivariate analysis. In summary, baseline pretreatment NLR and GPS are independently associated with OS in R/MHNSCC patients treated with nivolumab. Administration of nivolumab while maintaining the PS reflects a immune status of the host and leads to a good OS. en-copyright= kn-copyright= en-aut-name=ChikuieNobuyuki en-aut-sei=Chikuie en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamamotoTakao en-aut-sei=Hamamoto en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaTsutomu en-aut-sei=Ueda en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaruyaTakayuki en-aut-sei=Taruya en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KonoTakashi en-aut-sei=Kono en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FuruieHiromi en-aut-sei=Furuie en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshinoTakashi en-aut-sei=Ishino en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakenoSachio en-aut-sei=Takeno en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=2 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=3 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=4 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=8 en-affil=Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= en-keyword=neutrophil-to-lymphocyte ratio kn-keyword=neutrophil-to-lymphocyte ratio en-keyword=nivolumab kn-keyword=nivolumab en-keyword=Glasgow Prognostic Score kn-keyword=Glasgow Prognostic Score en-keyword=recurrent or metastatic head and neck squamous cell carcinoma (R/MHNSCC) kn-keyword=recurrent or metastatic head and neck squamous cell carcinoma (R/MHNSCC) END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=315 end-page=322 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Validity and Reliability of the Japanese Version of the 12-item Self-administered World Health Organization Disability Assessment Schedule (WHODAS) 2.0 in Patients with Schizophrenia en-subtitle= kn-subtitle= en-abstract= kn-abstract=It is necessary to assess functional impairment when treating schizophrenia. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) has been adopted as a measure of functional disability in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. This study was a secondary analysis from a cross-sectional study of health-related behaviors among patients with schizophrenia. We examined the validity and reliability of the Japanese version of the 12-item WHODAS 2.0 when self-administered by such patients. Participants were 350 outpatients with schizophrenia from a psychiatric hospital. The standard six-factor structure of the WHODAS 2.0 showed a good fit for these participants. The Cronbach’s alpha coefficient was 0.858, showing good internal consistency. The WHODAS 2.0 showed moderate correlations with the modified Global Assessment of Functioning and Kessler 6 scales (r=−0.434 and 0.555, respectively). The results of this study show that the Japanese version of the 12-item self-administered WHODAS 2.0 has good internal consistency and convergent validity among patients with schizophrenia. Further exploration of the usefulness of WHODAS 2.0 in clinical settings is needed. en-copyright= kn-copyright= en-aut-name=WadaRiho en-aut-sei=Wada en-aut-mei=Riho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaYuto en-aut-sei=Yamada en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakayaNaoki en-aut-sei=Nakaya en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimoriMaiko en-aut-sei=Fujimori en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SoRyuhei en-aut-sei=So en-aut-mei=Ryuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KodamaMasafumi en-aut-sei=Kodama en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiguchiYuji en-aut-sei=Higuchi en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KakedaKyoko en-aut-sei=Kakeda en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UchitomiYosuke en-aut-sei=Uchitomi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamadaNorihito en-aut-sei=Yamada en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=InagakiMasatoshi en-aut-sei=Inagaki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Health Sciences, Saitama Prefectural University kn-affil= affil-num=5 en-affil=Division of Health Care Research, Behavioral Sciences and Survivorship Research Group, National Cancer Center kn-affil= affil-num=6 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=7 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=8 en-affil=Care of Your Mind, Taiyo Hills Hospital kn-affil= affil-num=9 en-affil=Department of Neuropsychiatry, Kochi Medical School, Kochi University kn-affil= affil-num=10 en-affil=Innovation Center for Supportive, Palliative and Psychosocial Care, National Cancer Center Hospital kn-affil= affil-num=11 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Psychiatry, Faculty of Medicine, Shimane University kn-affil= en-keyword=disability kn-keyword=disability en-keyword=schizophrenia kn-keyword=schizophrenia en-keyword=validity kn-keyword=validity en-keyword=reliability kn-keyword=reliability en-keyword=WHODAS 2.0 kn-keyword=WHODAS 2.0 END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=289 end-page=297 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy and Safety of Early Intravenous Landiolol on Myocardial Salvage in Patients with ST-segment Elevation Myocardial Infarction before Primary Percutaneous Coronary Intervention: A Randomized Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Early treatment with an oral β-blocker is recommended in patients with a ST-segment–elevation myocardial infarction (STEMI). In this multicenter study, we evaluated the effects of a continuous administration of landiolol, an ultrashort-acting β-blocker, before primary percutaneous coronary intervention (PCI) on myocardial salvage and its safety in STEMI patients. A total of 47 Japanese patients with anterior or lateral STEMI undergoing a primary PCI within 12 h of symptom onset were randomized to receive intravenous landiolol (started at 3 μg/min/kg dose and continued to a total of 50 mg; n=23) or not (control; n=24). Patients with Killip class III or more were excluded. The primary outcome was the myocardial salvage index on cardiac magnetic resonance imaging (MRI) performed 5-7 days after the PCI. Cardiac MRI was performed in 35 patients (74%). The myocardial salvage index in the landiolol group was significantly greater than that in the control group (44.4±14.6% vs. 31.7±18.9%, respectively; p=0.04). There were no significant differences in adverse events at 24 h between the landiolol and control groups. A continuous administration of landiolol before a primary PCI may increase the degree of myocardial salvage without additional hemodynamic adverse effects within the first 24 h after STEMI. en-copyright= kn-copyright= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OsawaKazuhiro en-aut-sei=Osawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=MoriAtsushi en-aut-sei=Mori en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshikawaMasaki en-aut-sei=Yoshikawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkaTakefumi en-aut-sei=Oka en-aut-mei=Takefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchikawaKeishi en-aut-sei=Ichikawa en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiology, Tsuyama Central Hospital kn-affil= affil-num=5 en-affil=Department of Cardiology, Fukuyama City Hospital kn-affil= affil-num=6 en-affil=Department of Cardiology, Tsuyama Central Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=myocardial infarction kn-keyword=myocardial infarction en-keyword=landiolol kn-keyword=landiolol en-keyword= magnetic resonance imaging kn-keyword= magnetic resonance imaging en-keyword=STEMI kn-keyword=STEMI en-keyword=PCI kn-keyword=PCI END start-ver=1.4 cd-journal=joma no-vol=381 cd-vols= no-issue= article-no= start-page=335 end-page=361 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Darondeau–Pragacz formulas in complex cobordism en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this paper, we generalize the push-forward (Gysin) formulas for flag bundles in ordinary cohomology theory, which are due to Darondeau-Pragacz, to the complex cobordism theory. Then, we introduce the universal quadratic Schur functions, which are a generalization of the (ordinary) quadratic Schur functions introduced by Darondeau-Pragacz, and establish some Gysin formulas for the universal quadratic Schur functions as an application of our Gysin formulas. en-copyright= kn-copyright= en-aut-name=NakagawaMasaki en-aut-sei=Nakagawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaruseHiroshi en-aut-sei=Naruse en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=4 article-no= start-page=510 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210330 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification and Biochemical Characterization of High Mobility Group Protein 20A as a Novel Ca2+/S100A6 Target en-subtitle= kn-subtitle= en-abstract= kn-abstract=During screening of protein-protein interactions, using human protein arrays carrying 19,676 recombinant glutathione s-transferase (GST)-fused human proteins, we identified the high-mobility protein group 20A (HMG20A) as a novel S100A6 binding partner. We confirmed the Ca2+-dependent interaction of HMG20A with S100A6 by the protein array method, biotinylated S100A6 overlay, and GST-pulldown assay in vitro and in transfected COS-7 cells. Co-immunoprecipitation of S100A6 with HMG20A from HeLa cells in a Ca2+-dependent manner revealed the physiological relevance of the S100A6/HMG20A interaction. In addition, HMG20A has the ability to interact with S100A1, S100A2, and S100B in a Ca2+-dependent manner, but not with S100A4, A11, A12, and calmodulin. S100A6 binding experiments using various HMG20A mutants revealed that Ca2+/S100A6 interacts with the C-terminal region (residues 311-342) of HMG20A with stoichiometric binding (HMG20A:S100A6 dimer = 1:1). This was confirmed by the fact that a GST-HMG20A mutant lacking the S100A6 binding region (residues 311-347, HMG20A-Delta C) failed to interact with endogenous S100A6 in transfected COS-7 cells, unlike wild-type HMG20A. Taken together, these results identify, for the first time, HMG20A as a target of Ca2+/S100 proteins, and may suggest a novel linkage between Ca2+/S100 protein signaling and HMG20A function, including in the regulation of neural differentiation. en-copyright= kn-copyright= en-aut-name=YamamotoMaho en-aut-sei=Yamamoto en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoRina en-aut-sei=Kondo en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HozumiHaruka en-aut-sei=Hozumi en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DoiSeita en-aut-sei=Doi en-aut-mei=Seita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DendaMiwako en-aut-sei=Denda en-aut-mei=Miwako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KanayamaNaoki en-aut-sei=Kanayama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HatanoNaoya en-aut-sei=Hatano en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorishitaRyo en-aut-sei=Morishita en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, 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=Cell Free Sciences Co., Ltd. kn-affil= affil-num=6 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=Cell Free Sciences Co., Ltd. kn-affil= affil-num=10 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=S100 protein kn-keyword=S100 protein en-keyword=HMG20A kn-keyword=HMG20A en-keyword=protein-protein interaction kn-keyword=protein-protein interaction en-keyword=Ca2+-signal transduction kn-keyword=Ca2+-signal transduction en-keyword=genome-wide screening kn-keyword=genome-wide screening END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=2 article-no= start-page=187 end-page=197 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multiacquisition Variable-Resonance Image Combination Selective Can Improve Image Quality and Reproducibility for Metallic Implants in the Lumbar Spine en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this study is to evaluate how metallic artifacts in the lumbar spine can affect images obtained from magnetic resonance (MR) sequences. We performed a phantom experiment by scanning an agar containing an orthopedic metallic implant using 64-channel multidetector row computed tomography (CT) and a 3-tesla MR unit. We compared the reproducibility in each measurement, enlargement or reduction ratio of the CT and MR measurements, and signal deviation in each voxel from the control. The reproducibility on CT and multiacquisition variable-resonance image combination selective (MAVRIC SL) was good, but that on the other MR sequences showed either fixed bias or proportional bias. The reduction ratios of the distance between the nails were significantly smaller in MAVRIC SL than in the other MR sequences after CT measurements (p<0.001, respectively). MAVRIC SL was able to reduce the metallic artifact, permitting observation of the tissue surrounding the metal with good reproducibility. en-copyright= kn-copyright= en-aut-name=FujiwaraYuta en-aut-sei=Fujiwara en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SasakiTomoaki en-aut-sei=Sasaki en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MutoYuki en-aut-sei=Muto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiranoMasaki en-aut-sei=Hirano en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamizakiRyo en-aut-sei=Kamizaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurakamiKaito en-aut-sei=Murakami en-aut-mei=Kaito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiuraNaoya en-aut-sei=Miura en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujibuchiYutaka en-aut-sei=Fujibuchi en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhmukaiNayu en-aut-sei=Ohmukai en-aut-mei=Nayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UedaNao en-aut-sei=Ueda en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SugimotoKouhei en-aut-sei=Sugimoto en-aut-mei=Kouhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OtaKazuhiro en-aut-sei=Ota en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KamihoriuchiYoshiki en-aut-sei=Kamihoriuchi en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SasakiTomoko en-aut-sei=Sasaki en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KaneshigeSouichirou en-aut-sei=Kaneshige en-aut-mei=Souichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Division of Clinical Radiology Service, Okayama Central Hospital kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University 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 Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=12 en-affil=Division of Clinical Radiology Service, Okayama Central Hospital kn-affil= affil-num=13 en-affil=Division of Clinical Radiology Service, Okayama Central Hospital kn-affil= affil-num=14 en-affil=Division of Clinical Radiology Service, Okayama Central Hospital kn-affil= affil-num=15 en-affil=Department of Radiology, Okayama Central Hospital kn-affil= en-keyword=metallic artifact reduction kn-keyword=metallic artifact reduction en-keyword=implant kn-keyword=implant en-keyword=MAVRIC SL kn-keyword=MAVRIC SL END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue= article-no= start-page=100044 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural basis of enzyme activity regulation by the propeptide of l-lysine α-oxidase precursor from Trichoderma viride en-subtitle= kn-subtitle= en-abstract= kn-abstract=Harmuful proteins are usually synthesized as inactive precursors and are activated by proteolytic processing. l-Amino acid oxidase (LAAO) is a flavoenzyme that catalyzes the oxidative deamination of l-amino acid to produce a 2-oxo acid with ammonia and highly toxic hydrogen peroxide and, therefore, is expressed as a precursor. The LAAO precursor shows significant variation in size and the cleavage pattern for activation. However, the molecular mechanism of how the propeptide suppresses the enzyme activity remains unclear except for deaminating/decarboxylating Pseudomonasl-phenylalanine oxidase (PAO), which has a short N-terminal propeptide composed of 14 residues. Here we show the inactivation mechanism of the l-lysine oxidase (LysOX) precursor (prLysOX), which has a long N-terminal propeptide composed of 77 residues, based on the crystal structure at 1.97 Å resolution. The propeptide of prLysOX indirectly changes the active site structure to inhibit the enzyme activity. prLysOX retains weak enzymatic activity with strict specificity for l-lysine and shows raised activity in acidic conditions. The structures of prLysOX crystals that soaked in a solution with various concentrations of l-lysine have revealed that prLysOX can adopt two conformations; one is the inhibitory form, and the other is very similar to mature LysOX. The propeptide region of the latter form is disordered, and l-lysine is bound to the latter form. These results indicate that prLysOX uses a different strategy from PAO to suppress the enzyme activity and suggest that prLysOX can be activated quickly in response to the environmental change without proteolytic processing. en-copyright= kn-copyright= en-aut-name=KitagawaMasaki en-aut-sei=Kitagawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoNanako en-aut-sei=Ito en-aut-mei=Nanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoYuya en-aut-sei=Matsumoto en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoMasaya en-aut-sei=Saito en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraTakashi en-aut-sei=Tamura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KusakabeHitoshi en-aut-sei=Kusakabe en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InagakiKenji en-aut-sei=Inagaki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ImadaKatsumi en-aut-sei=Imada en-aut-mei=Katsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Macromolecular Science, Graduate School of Science, Osaka University kn-affil= affil-num=2 en-affil=Department of Macromolecular Science, Graduate School of Science, Osaka University kn-affil= affil-num=3 en-affil=Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Enzyme Sensor Co., Ltd. kn-affil= affil-num=7 en-affil=Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Macromolecular Science, Graduate School of Science, Osaka University kn-affil= en-keyword=L-Lysine α-oxidase kn-keyword=L-Lysine α-oxidase en-keyword=Crystal structure kn-keyword=Crystal structure en-keyword=Precursor kn-keyword=Precursor en-keyword=Substrate recognition kn-keyword=Substrate recognition END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=2 article-no= start-page=213 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigation of Factors Affecting Early Quality of Life of Patients after Breast Cancer Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: The purpose of this study was to investigate factors related to early quality of life (QOL) three months after surgery in breast cancer patients with axillary lymph node dissection. Methods: The subjects of this study were 195 consecutive patients who underwent axillary lymph node dissection for breast cancer. Age, body mass index, level of lymph node dissection, marriage, children, co-resident household members, neoadjuvant chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, upper limb function (disabilities of the arm, shoulder, and hand (DASH)), and QOL (European Organization for the Treatment and Research of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)) were evaluated. For each item of the EORTC QLQ-C30, compared with preoperative status and three months after surgery, those who improved or remained unchanged in the three months after surgery were classified as the maintenance and improved groups, and those with worsening status were classified as the worsened group. Results: Age, level of lymph node dissection, DASH, neoadjuvant chemotherapy, postoperative chemotherapy, and postoperative radiotherapy were significantly associated with QOL (p < 0.05). Conclusions: The early QOL of postoperative patients with breast cancer is affected by multiple factors, such as upper limb function and postoperative chemotherapy, and thus comprehensive intervention is required. en-copyright= kn-copyright= en-aut-name=AkezakiYoshiteru en-aut-sei=Akezaki en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikuuchiMasato en-aut-sei=Kikuuchi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TominagaRitsuko en-aut-sei=Tominaga en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurokawaHideaki en-aut-sei=Kurokawa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoMasaki en-aut-sei=Okamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamadaMakiko en-aut-sei=Hamada en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=OhsumiShozo en-aut-sei=Ohsumi en-aut-mei=Shozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugiharaShinsuke en-aut-sei=Sugihara en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Physical Therapy, Kochi Professional University of Rehabilitation kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=7 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=10 en-affil=Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= en-keyword=quality of life kn-keyword=quality of life en-keyword=breast cancer kn-keyword=breast cancer en-keyword=neoadjuvant chemotherapy kn-keyword=neoadjuvant chemotherapy en-keyword=postoperative chemotherapy kn-keyword=postoperative chemotherapy en-keyword=postoperative radiotherapy kn-keyword=postoperative radiotherapy END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=20857 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lokiarchaeota archaeon schizorhodopsin-2 (LaSzR2) is an inward proton pump displaying a characteristic feature of acid-induced spectral blue-shift en-subtitle= kn-subtitle= en-abstract= kn-abstract=The photoreactive protein rhodopsin is widespread in microorganisms and has a variety of photobiological functions. Recently, a novel phylogenetically distinctive group named 'schizorhodopsin (SzR)' has been identified as an inward proton pump. We performed functional and spectroscopic studies on an uncharacterised schizorhodopsin from the phylum Lokiarchaeota archaeon. The protein, LaSzR2, having an all-trans-retinal chromophore, showed inward proton pump activity with an absorption maximum at 549 nm. The pH titration experiments revealed that the protonated Schiff base of the retinal chromophore (Lys188, pK(a)=12.3) is stabilised by the deprotonated counterion (presumably Asp184, pK(a)=3.7). The flash-photolysis experiments revealed the presence of two photointermediates, K and M. A proton was released and uptaken from bulk solution upon the formation and decay of the M intermediate. During the M-decay, the Schiff base was reprotonated by the proton from a proton donating residue (presumably Asp172). These properties were compared with other inward (SzRs and xenorhodopsins, XeRs) and outward proton pumps. Notably, LaSzR2 showed acid-induced spectral 'blue-shift' due to the protonation of the counterion, whereas outward proton pumps showed opposite shifts (red-shifts). Thus, we can distinguish between inward and outward proton pumps by the direction of the acid-induced spectral shift. en-copyright= kn-copyright= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=HasegawaMasumi en-aut-sei=Hasegawa en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamaMasaki en-aut-sei=Nakama en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuriharaMarie en-aut-sei=Kurihara en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KikukawaTakashi en-aut-sei=Kikukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=3 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Advanced Life Science, Hokkaido University kn-affil= affil-num=7 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=28 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210113 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effectiveness, safety, and factors associated with the clinical success of endoscopic biliary drainage for patients with hepatocellular carcinoma: a retrospective multicenter study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Only a few reports have assessed the effectiveness of endoscopic biliary drainage (EBD) in hepatocellular carcinoma (HCC) patients with obstructive jaundice and liver dysfunction.
Methods
This was a retrospective study based on the clinical databases from the Okayama University Hospital and 10 affiliated hospitals. All patients received EBD for jaundice or liver dysfunction. The indication for EBD was aggravation of jaundice or liver dysfunction with intrahepatic bile duct (IHBD) dilation. The technical and clinical success rate, complications, factors associated with clinical failure, and survival duration were evaluated.
Results
A total of 107 patients were enrolled in this study. Technical success was achieved in 105 of 107 patients (98.1%). Clinical success was achieved in 85 of 105 patients (81%). Complications related to endoscopic retrograde cholangiography (ERC) occurred in 3 (2.8%) patients. Child–Pugh class C (odds ratio 3.90, 95% confidence interval [CI] 1.47–10.4, p = 0.0046) was the only factor associated with clinical failure, irrespective of successful drainage. The median survival duration was significantly longer in patients with clinical success than in those without clinical success (5.0 months vs. 0.93 months; hazard ratio [HR] 3.2, 95% CI 1.87–5.37). HCC Stage I/II/III (HR 0.57, CI 0.34–0.95, p = 0.032), absence of portal thrombosis (HR 0.52, CI 0.32–0.85, p = 0.0099), and clinical success (HR 0.39, CI 0.21–0.70, p = 0.0018) were significant factors associated with a long survival.
Conclusions
EBD for obstructive jaundice and liver dysfunction in patients with HCC can be performed safely with a high technical success rate. Clinical success can improve the survival duration, even in patients expected to have a poor prognosis. en-copyright= kn-copyright= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UekiToru en-aut-sei=Ueki en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaEtsuji en-aut-sei=Ishida en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakataniMasahiro en-aut-sei=Takatani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiMasakuni en-aut-sei=Fujii en-aut-mei=Masakuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatoMasaki en-aut-sei=Wato en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=HaradaRyo en-aut-sei=Harada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsugenoHirofumi en-aut-sei=Tsugeno en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsubaraMinoru en-aut-sei=Matsubara en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsushitaHiroshi en-aut-sei=Matsushita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Kurashiki Central Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Tsuyama Central Hospital kn-affil= affil-num=11 en-affil=Department of Internal Medicine, Sumitomo Besshi Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterology, Okayama City Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Endoscopic retrograde cholangiopancreatography kn-keyword=Endoscopic retrograde cholangiopancreatography en-keyword=Jaundice kn-keyword=Jaundice en-keyword=Hepatocellular carcinoma kn-keyword=Hepatocellular carcinoma en-keyword=Liver dysfunction kn-keyword=Liver dysfunction END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=1 article-no= start-page=217 end-page=227 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background:
Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer’s disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid- β (Aβ), plasma tau, and serum antibodies for Aβ1 - 42 are not yet well established.
Objective:
We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology.
Methods:
With only 1.5μl of serum, we examined a new target plate “BLOTCHIP®” plus a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n = 100), MCI (n = 60), and AD (n = 99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains.
Results:
Apart from Aβ or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (***p < 0.001). MMSE score was well correlated to brain Aβ deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains.
Conclusion:
The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage. en-copyright= kn-copyright= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShangJingwei en-aut-sei=Shang en-aut-mei=Jingwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiXiaowen en-aut-sei=Shi en-aut-mei=Xiaowen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IkedaMasaki en-aut-sei=Ikeda en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IkedaYoshio en-aut-sei=Ikeda en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkamotoKoichi en-aut-sei=Okamoto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShojiMikio en-aut-sei=Shoji en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakatamaMasamitsu en-aut-sei=Takatama en-aut-mei=Masamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KojoMotohisa en-aut-sei=Kojo en-aut-mei=Motohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KurodaTakeshi en-aut-sei=Kuroda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OnoKenjiro en-aut-sei=Ono en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KimuraNoriyuki en-aut-sei=Kimura en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MatsubaraEtsuro en-aut-sei=Matsubara en-aut-mei=Etsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OsakadaYosuke en-aut-sei=Osakada en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=WakutaniYosuke en-aut-sei=Wakutani en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TakaoYoshiki en-aut-sei=Takao en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HigashiYasuto en-aut-sei=Higashi en-aut-mei=Yasuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=AsadaKyoichi en-aut-sei=Asada en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=SengaTakehito en-aut-sei=Senga en-aut-mei=Takehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name= LeeLyang-Ja en-aut-sei= Lee en-aut-mei=Lyang-Ja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TanakaKenji en-aut-sei=Tanaka en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=9 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama City Hospital, Okayama kn-affil= affil-num=11 en-affil=Department of Neurology, Gunma University, Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Neurology, Gunma University, Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Neurology, Geriatrics Research Institute and Hospital kn-affil= affil-num=14 en-affil=Department of Neurology, Geriatrics Research Institute and Hospital kn-affil= affil-num=15 en-affil=Department of Neurology, Geriatrics Research Institute and Hospital kn-affil= affil-num=16 en-affil=Department of Neurology, Ako Chuo Hospital kn-affil= affil-num=17 en-affil=Division of Neurology, Department of Medicine, Showa University, School of Medicine kn-affil= affil-num=18 en-affil=Division of Neurology, Department of Medicine, Showa University, School of Medicine kn-affil= affil-num=19 en-affil=Department of Neurology, Faculty of Medicine, Oita University kn-affil= affil-num=20 en-affil=Department of Neurology, Faculty of Medicine, Oita University kn-affil= affil-num=21 en-affil=Department of Neurology, Kurashiki Heisei Hospital kn-affil= affil-num=22 en-affil=Department of Neurology, Kurashiki Heisei Hospital kn-affil= affil-num=23 en-affil=Department of Neurology, Kurashiki Heisei Hospital kn-affil= affil-num=24 en-affil=Department of Neurology, Himeji Central Hospital kn-affil= affil-num=25 en-affil=Membrane Protein and Ligand Analysis Center, Protosera Inc., kn-affil= affil-num=26 en-affil=Membrane Protein and Ligand Analysis Center, Protosera Inc., kn-affil= affil-num=27 en-affil=Membrane Protein and Ligand Analysis Center, Protosera Inc., kn-affil= affil-num=28 en-affil=Membrane Protein and Ligand Analysis Center, Protosera Inc., kn-affil= en-keyword=Alzheimer’s disease kn-keyword=Alzheimer’s disease en-keyword=biomarker kn-keyword=biomarker en-keyword=coagulation kn-keyword=coagulation en-keyword=complement kn-keyword=complement en-keyword=MALDI-TOF kn-keyword=MALDI-TOF en-keyword=mild cognitive impairment kn-keyword=mild cognitive impairment en-keyword=neuroinflammation kn-keyword=neuroinflammation en-keyword=peptidome kn-keyword=peptidome en-keyword=plasticity kn-keyword=plasticity END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue= article-no= start-page=100595 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202009 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HAMAMATSU-ICG study: Protocol for a phase III, multicentre, single-arm study to assess the usefulness of indocyanine green fluorescent lymphography in assessing secondary lymphoedema en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction
Secondary lymphoedema of the extremities is an important quality-of-life issue for patients who were treated for their malignancies. Indocyanine green (ICG) fluorescent lymphography may be helpful for assessing lymphoedema and for planning lymphaticovenular anastomosis (LVA). The objective of the present clinical trial is to confirm whether or not ICG fluorescent lymphography using the near-infrared monitoring camera is useful for assessing the indication for LVA, for the identification of the lymphatic vessels before the conduct of LVA, and for the confirmation of the patency of the anastomosis site during surgery.
Methods and analysis
This trial is a phase III, multicentre, single-arm, open-label clinical trial to assess the efficacy and safety of ICG fluorescent lymphography when assessing and treating lymphoedema of patients with secondary lymphoedema who are under consideration for LVA. The primary endpoint is the identification rate of the lymphatic vessels at the incision site based on ICG fluorescent lymphograms obtained before surgery. The secondary endpoints are 1) the sensitivity and specificity of dermal back flow determined by ICG fluorescent lymphography as compared with 99mTc lymphoscintigraphy—one of the standard diagnostic methods and 2) the usefulness of ICG fluorescent lymphography when confirming the patency of the anastomosis site after LVA.
Ethics and dissemination
The protocol for the study was approved by the Institutional Review Board of each institution. The trial was filed for and registered at the Pharmaceuticals and Medical Devices Agency in Japan. The trial is currently on-going and is scheduled to end in June 2020. en-copyright= kn-copyright= en-aut-name=AkitaShinsuke en-aut-sei=Akita en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UnnoNaoki en-aut-sei=Unno en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaegawaJiro en-aut-sei=Maegawa en-aut-mei=Jiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KimataYoshihiro en-aut-sei=Kimata en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukamizuHidekazu en-aut-sei=Fukamizu en-aut-mei=Hidekazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YabukiYuichiro en-aut-sei=Yabuki en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShinaokaAkira en-aut-sei=Shinaoka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SanoMasaki en-aut-sei=Sano en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawasakiYohei en-aut-sei=Kawasaki en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraTadami en-aut-sei=Fujiwara en-aut-mei=Tadami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HanaokaHideki en-aut-sei=Hanaoka en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MitsukawaNobuyuki en-aut-sei=Mitsukawa 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 Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Vascular Surgery, Hamamatsu Medical Center kn-affil= affil-num=3 en-affil=Department of Plastic and Reconstructive Surgery, Yokohama City University, Graduate School of Medicin kn-affil= affil-num=4 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Plastic and Reconstructive Surgery, Hamamatsu University School of Medicine kn-affil= affil-num=6 en-affil=Department of Plastic and Reconstructive Surgery, Yokohama City University, Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Second Department of Surgery, Hamamatsu University School of Medicine kn-affil= affil-num=9 en-affil=Clinical Research Center, Chiba University Hospital kn-affil= affil-num=10 en-affil=Clinical Research Center, Chiba University Hospital kn-affil= affil-num=11 en-affil=Clinical Research Center, Chiba University Hospital kn-affil= affil-num=12 en-affil=Department of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of Medicine kn-affil= en-keyword=Indocyanine green fluorescent lymphography kn-keyword=Indocyanine green fluorescent lymphography en-keyword=Secondary lymphoedema kn-keyword=Secondary lymphoedema en-keyword=Lymphaticovenular anastomosis kn-keyword=Lymphaticovenular anastomosis END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue= article-no= start-page=100571 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202011 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of patient characteristics on the efficacy and safety of landiolol in patients with sepsis-related tachyarrhythmia: Subanalysis of the J-Land 3S randomised controlled study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
The J-Land 3S trial demonstrated that landiolol is effective and tolerated for treating sepsis-related tachyarrhythmias. Patient characteristics (e.g. baseline heart rate [HR], type of tachyarrhythmia, and concomitant disorders) may impact the outcomes of landiolol therapy. We performed subanalyses of J-Land 3S to evaluate the impact of patient characteristics on the efficacy and safety of landiolol for treating sepsis-related tachyarrhythmia.
Methods
Patients (≥20 years old; N = 151) hospitalised with sepsis at 54 participating hospitals in Japan with HR ≥100 beats/min for ≥10 min accompanied by diagnosis of tachyarrhythmia were randomised 1:1 to conventional sepsis therapy alone (control group) or conventional sepsis therapy plus landiolol (landiolol group). The efficacy and safety of landiolol were assessed in prespecified analyses of patients divided into subgroups by baseline characteristics and in post hoc, multivariate analyses with adjustment for age and HR at baseline.
Findings
The percentage of patients with HR of 60–94 beats/min at 24 h after randomisation (primary endpoint) was greater in the landiolol group in most subgroups in univariate unadjusted analyses and in multivariate logistic regression. The incidence of new-onset arrhythmia by 168 h and mortality by 28 days were also lower in the landiolol group in most subgroups in univariate and multivariate Cox proportional hazards models. No subgroups showed a markedly higher incidence of adverse events in univariate or multivariate logistic regression analyses. en-copyright= kn-copyright= en-aut-name=MatsudaNaoyuki en-aut-sei=Matsuda en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishidaOsamu en-aut-sei=Nishida en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniguchiTakumi en-aut-sei=Taniguchi en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkajimaMasaki en-aut-sei=Okajima en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OguraHiroshi en-aut-sei=Ogura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamadaYoshitsugu en-aut-sei=Yamada en-aut-mei=Yoshitsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NaganoTetsuji en-aut-sei=Nagano en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IchikawaAkira en-aut-sei=Ichikawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KakihanaYasuyuki en-aut-sei=Kakihana en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=J-Land 3S Study Group en-aut-sei=J-Land 3S Study Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Emergency & Critical Care Medicine, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Anesthesiology & Critical Care Medicine, Fujita Health University School of Medicine kn-affil= affil-num=3 en-affil=Department of Anesthesiology & Intensive Care Medicine, Kanazawa University kn-affil= affil-num=4 en-affil=Intensive Care Unit, Kanazawa University Hospital kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Anesthesiology and Pain Relief Center, The University of Tokyo Hospital kn-affil= affil-num=8 en-affil=Clinical Development Planning, Ono Pharmaceutical Co., Ltd. kn-affil= affil-num=9 en-affil=Clinical Development Planning, Ono Pharmaceutical Co., Ltd. kn-affil= affil-num=10 en-affil=Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences kn-affil= affil-num=11 en-affil= kn-affil= en-keyword=Ultra-short-acting β1-selective antagonist kn-keyword=Ultra-short-acting β1-selective antagonist en-keyword=Heart rate kn-keyword=Heart rate en-keyword=Mortality kn-keyword=Mortality en-keyword=Adverse events kn-keyword=Adverse events en-keyword=Septic shock kn-keyword=Septic shock END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=16 article-no= start-page=e015103 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200818 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Luseogliflozin on Heart Failure With Preserved Ejection Fraction in Patients With Diabetes Mellitus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Effects of sodium‐glucose cotransporter 2 inhibitors on reducing hospitalization for heart failure have been reported in randomized controlled trials, but their effects on patients with heart failure with preserved ejection fraction (HFpEF) are unknown. This study aimed to evaluate the drug efficacy of luseogliflozin, a sodium‐glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus and HFpEF.
Methods and Results
We performed a multicenter, open‐label, randomized, controlled trial for comparing luseogliflozin 2.5 mg once daily with voglibose 0.2 mg 3 times daily in patients with type 2 diabetes mellitus suffering from HFpEF (left ventricular ejection fraction >45% and BNP [B‐type natriuretic peptide] concentrations ≥35 pg/mL) in a 1:1 randomization fashion. The primary outcome was the difference from baseline in BNP levels after 12 weeks of treatment between the 2 drugs. A total of 173 patients with diabetes mellitus and HFpEF were included. Of these, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in BNP concentrations after 12 weeks from baseline between the 2 groups. The ratio of the mean BNP value at week 12 to the baseline value was 0.79 in the luseogliflozin group and 0.87 in the voglibose group (percent change, −9.0% versus −1.9%; ratio of change with luseogliflozin versus voglibose, 0.93; 95% CI, 0.78–1.10; P=0.26).
Conclusion
In patients with type 2 diabetes mellitus and HFpEF, there is no significant difference in the degree of reduction in BNP concentrations after 12 weeks between luseogliflozin and voglibose. en-copyright= kn-copyright= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro 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=KiharaHajime en-aut-sei=Kihara en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HataYoshiki en-aut-sei=Hata en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaganoToshihiko en-aut-sei=Nagano en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakaishiAtsushi en-aut-sei=Takaishi en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TodaHironobu en-aut-sei=Toda en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NanbaSeiji en-aut-sei=Nanba en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraYoichi en-aut-sei=Nakamura en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakuragiSatoru en-aut-sei=Sakuragi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MinagawaTaro en-aut-sei=Minagawa en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KawaiYusuke en-aut-sei=Kawai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= en-aut-name=YoshikawaMasaki en-aut-sei=Yoshikawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 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=17 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Kihara Cardiovascular Clinic kn-affil= affil-num=4 en-affil=Department of Cardiology, Minamino Cardiovascular Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Iwasa Hospital kn-affil= affil-num=6 en-affil=Department of Cardiology, Mitoyo General Hospital kn-affil= affil-num=7 en-affil=Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiology, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Specified Clinic of Soyokaze Cardiovascular Medicine and Diabetes Care kn-affil= affil-num=10 en-affil=Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Iwakuni Clinical Center kn-affil= affil-num=12 en-affil=Department of Internal Medicine, Minagawa Cardiovascular Clinic kn-affil= affil-num=13 en-affil=Department of Cardiovascular Medicine, Okayama City Hospital kn-affil= affil-num=14 en-affil=Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=16 en-affil=Department of Cardiology, Fukuyama City Hospital kn-affil= affil-num=17 en-affil=Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences kn-affil= en-keyword=B-type natriuretic peptide kn-keyword=B-type natriuretic peptide en-keyword=diabetes mellitus kn-keyword=diabetes mellitus en-keyword=heart failure kn-keyword=heart failure en-keyword=sodium-glucose cotransporter 2 inhibitor kn-keyword=sodium-glucose cotransporter 2 inhibitor END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=1 article-no= start-page=61 end-page=86 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Defining relations of 3-dimensional quadratic AS-regular algebras en-subtitle= kn-subtitle= en-abstract= kn-abstract=Classification of AS-regular algebras is one of the main interests in non-commutative algebraic geometry. Recently, a complete list of superpotentials (defining relations) of all 3-dimensional AS-regular algebras which are Calabi-Yau was given by Mori-Smith (the quadratic case) and Mori-Ueyama (the cubic case), however, no complete list of defining relations of all 3-dimensional AS-regular algebras has not appeared in the literature. In this paper, we give all possible defining relations of 3-dimensional quadratic AS-regular algebras. Moreover, we classify them up to isomorphism and up to graded Morita equivalence in terms of their defining relations in the case that their point schemes are not elliptic curves. In the case that their point schemes are elliptic curves, we give conditions for isomorphism and graded Morita equivalence in terms of geometric data. en-copyright= kn-copyright= en-aut-name=ItabaAyako en-aut-sei=Itaba en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsunoMasaki en-aut-sei=Matsuno en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Mathematics, faculty of Science, Tokyo University of Science kn-affil= affil-num=2 en-affil=Graduate School of Science and Technology, Shizuoka University kn-affil= en-keyword=AS-regular algebras kn-keyword=AS-regular algebras en-keyword=geometric algebras kn-keyword=geometric algebras en-keyword=quadratic algebras kn-keyword=quadratic algebras en-keyword=nodal cubic curves kn-keyword=nodal cubic curves en-keyword=elliptic curves kn-keyword=elliptic curves en-keyword=Hesse form kn-keyword=Hesse form en-keyword=Sklyanin algebras kn-keyword=Sklyanin algebras END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=16490 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spred2-deficiency enhances the proliferation of lung epithelial cells and alleviates pulmonary fibrosis induced by bleomycin en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mitogen-activated protein kinase (MAPK) pathways are involved in many cellular processes, including the development of fibrosis. Here, we examined the role of Sprouty-related EVH-1-domain-containing protein (Spred) 2, a negative regulator of the MAPK-ERK pathway, in the development of bleomycin (BLM)-induced pulmonary fibrosis (PF). Compared to WT mice, Spred2−/− mice developed milder PF with increased proliferation of bronchial epithelial cells. Spred2−/− lung epithelial cells or MLE-12 cells treated with spred2 siRNA proliferated faster than control cells in vitro. Spred2−/− and WT macrophages produced similar levels of TNFα and MCP-1 in response to BLM or lipopolysaccharide and myeloid cell-specific deletion of Spred2 in mice had no effect. Spred2−/− fibroblasts proliferated faster and produced similar levels of MCP-1 compared to WT fibroblasts. Spred2 mRNA was almost exclusively detected in bronchial epithelial cells of naïve WT mice and it accumulated in approximately 50% of cells with a characteristic of Clara cells, 14 days after BLM treatment. These results suggest that Spred2 is involved in the regulation of tissue repair after BLM-induced lung injury and increased proliferation of lung bronchial cells in Spred2−/− mice may contribute to faster tissue repair. Thus, Spred2 may present a new therapeutic target for the treatment of PF. en-copyright= kn-copyright= en-aut-name=KawaraAkina en-aut-sei=Kawara en-aut-mei=Akina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MizutaRyo en-aut-sei=Mizuta en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=ItoToshihiro en-aut-sei=Ito en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiChunning en-aut-sei=Li en-aut-mei=Chunning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraKaoru en-aut-sei=Nakamura en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SunCuiming en-aut-sei=Sun en-aut-mei=Cuiming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KuwabaraMasaki en-aut-sei=Kuwabara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitabatakeMasahiro en-aut-sei=Kitabatake en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Immunology, Nara Medical University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Immunology, Nara Medical University kn-affil= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 affil-num=11 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= en-keyword=Cell signalling kn-keyword=Cell signalling en-keyword=Mechanisms of disease kn-keyword=Mechanisms of disease END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=8 article-no= start-page=1810 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200730 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ligation of MHC Class II Induces PKC-Dependent Clathrin-Mediated Endocytosis of MHC Class II en-subtitle= kn-subtitle= en-abstract= kn-abstract=In addition to antigen presentation to CD4(+)T cells, aggregation of cell surface major histocompatibility complex class II (MHC-II) molecules induces signal transduction in antigen presenting cells that regulate cellular functions. We previously reported that crosslinking of MHC-II induced the endocytosis of MHC-II, which was associated with decreased surface expression levels in murine dendritic cells (DCs) and resulted in impaired activation of CD4(+)T cells. However, the downstream signal that induces MHC-II endocytosis remains to be elucidated. In this study, we found that the crosslinking of MHC-II induced intracellular Ca(2+)mobilization, which was necessary for crosslinking-induced MHC-II endocytosis. We also found that these events were suppressed by inhibitors of Syk and phospholipase C (PLC). Treatments with a phorbol ester promoted MHC-II endocytosis, whereas inhibitors of protein kinase C (PKC) suppressed crosslinking-induced endocytosis of MHC-II. These results suggest that PKC could be involved in this process. Furthermore, crosslinking-induced MHC-II endocytosis was suppressed by inhibitors of clathrin-dependent endocytosis. Our results indicate that the crosslinking of MHC-II could stimulate Ca(2+)mobilization and induce the clathrin-dependent endocytosis of MHC-II in murine DCs. en-copyright= kn-copyright= en-aut-name=MasakiKento en-aut-sei=Masaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirakiYuhji en-aut-sei=Hiraki en-aut-mei=Yuhji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnishiHiroka en-aut-sei=Onishi en-aut-mei=Hiroka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatohYuka en-aut-sei=Satoh en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RochePaul A. en-aut-sei=Roche en-aut-mei=Paul A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaSatoshi en-aut-sei=Tanaka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Immunobiology, Faculty of Pharmacy and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Experimental Immunology Branch, National Cancer Institute, National Institutes of Health kn-affil= affil-num=6 en-affil=Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=MHC-II kn-keyword=MHC-II en-keyword=dendritic cells kn-keyword=dendritic cells en-keyword=endocytosis kn-keyword=endocytosis en-keyword=crosslink kn-keyword=crosslink en-keyword=PKC kn-keyword=PKC END start-ver=1.4 cd-journal=joma no-vol=1 cd-vols= no-issue=2 article-no= start-page=100053 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200613 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protocol for Genome Editing to Produce Multiple Mutants in Wheat en-subtitle= kn-subtitle= en-abstract= kn-abstract=Here, we describe a protocol for producing multiple recessive mutants via genome editing in hexaploid wheat (Triticum aestivum) cv. Fielder. Using Agrobacterium-delivered CRISPR/Cas9 and three sub-genome-specific primer sets, all possible combinations of single, double, and triple transgene-free mutants can be generated. The technique for acceleration of generation advancement with embryo culture reduces time for mutant production. The mutants produced by this protocol can be used for the analysis of gene function and crop improvement. For complete details on the use and execution of this protocol, please refer to Abe et al. (2019). en-copyright= kn-copyright= en-aut-name=AbeFumitaka en-aut-sei=Abe en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshidaYuji en-aut-sei=Ishida en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EndoMasaki en-aut-sei=Endo en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KomariToshihiko en-aut-sei=Komari en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokiSeiichi en-aut-sei=Toki en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Basic Research, Institute of Crop Science, NARO kn-affil= affil-num=2 en-affil=Plant Innovation Center, Japan Tobacco Inc. kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Division of Applied Genetics, Institute of Agrobiological Sciences, NARO kn-affil= affil-num=5 en-affil=Plant Innovation Center, Japan Tobacco Inc. kn-affil= affil-num=6 en-affil=Division of Applied Genetics, Institute of Agrobiological Sciences, NARO kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=4 article-no= start-page=293 end-page=299 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Preoperative Use of Alpha-1 Receptor Blockers in Male Patients Undergoing Extracorporeal Shock Wave Lithotripsy for a Ureteral Calculus en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this retrospective single-center cohort study, we investigated the impact of preoperative use of an alpha-1 adrenergic receptor (AR) blocker on the outcome of single-session extracorporeal shock wave lithotripsy (SWL) in 193 male patients who underwent SWL for a single ureteral calculus between 2006 and 2016. We reviewed their medical records to obtain the data on the preoperative use of alpha-1 AR blockers. The primary outcome was treatment success after single-session SWL. We performed a multivariable logistic regression analysis adjusting for clinically important confounders to examine the association between preoperative use of alpha-1 AR blockers and the treatment success of SWL. Among the 193 patients, 15 (7.8%) were taking an alpha-1 AR blocker preoperatively. A multivariable analysis showed that preoperative use of an alpha-1 AR blocker was a significant negative predictor for treatment success of SWL (adjusted odds ratio 0.17; 95% confidence intervals, 0.04-0.74). Our findings suggest that the preoperative use of an alpha-1 AR blocker was a negative predictor of treatment success of SWL in male patients with a single ureteral calculus. Clinicians should pay more attention to the preoperative drug use in determining an appropriate stone therapy modality. en-copyright= kn-copyright= en-aut-name=YoshiokaTakashi en-aut-sei=Yoshioka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmaeKenji en-aut-sei=Omae en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=InoueYosuke en-aut-sei=Inoue en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugimotoMorito en-aut-sei=Sugimoto en-aut-mei=Morito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OedaTadashi en-aut-sei=Oeda en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UeharaShinya en-aut-sei=Uehara en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=FukuharaShunichi en-aut-sei=Fukuhara en-aut-mei=Shunichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University kn-affil= affil-num=2 en-affil=Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University kn-affil= affil-num=3 en-affil=Department of Urology, Onomichi Municipal Hospital kn-affil= affil-num=4 en-affil=Department of Urology, Onomichi Municipal Hospital kn-affil= affil-num=5 en-affil=Department of Urology, Onomichi Municipal Hospital kn-affil= affil-num=6 en-affil=Department of Urology, Onomichi Municipal Hospital kn-affil= affil-num=7 en-affil=Department of Urology, Kawasaki Medical School General Medical Center 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=Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University kn-affil= en-keyword=urolithiasis kn-keyword=urolithiasis en-keyword=extracorporeal shockwave therapy kn-keyword=extracorporeal shockwave therapy en-keyword=adrenergic alpha-1 receptor antagonists kn-keyword=adrenergic alpha-1 receptor antagonists END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue= article-no= start-page=461 end-page=473 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Additional kernel observer: privilege escalation attack prevention mechanism focusing on system call privilege changes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cyberattacks, especially attacks that exploit operating system vulnerabilities, have been increasing in recent years. In particular, if administrator privileges are acquired by an attacker through a privilege escalation attack, the attacker can operate the entire system and cause serious damage. In this paper, we propose an additional kernel observer (AKO) that prevents privilege escalation attacks that exploit operating system vulnerabilities. We focus on the fact that a process privilege can be changed only by specific system calls. AKO monitors privilege information changes during system call processing. If AKO detects a privilege change after system call processing, whereby the invoked system call does not originally change the process privilege, AKO regards the change as a privilege escalation attack and applies countermeasures against it. AKO can therefore prevent privilege escalation attacks. Introducing the proposed method in advance can prevent this type of attack by changing any process privilege that was not originally changed in a system call, regardless of the vulnerability type. In this paper, we describe the design and implementation of AKO for Linux x86 64-bit. Moreover, we show that AKO can be expanded to prevent the falsification of various data in the kernel space. Then, we present an expansion example that prevents the invalidation of Security-Enhanced Linux. Finally, our evaluation results show that AKO is effective against privilege escalation attacks, while maintaining low overhead. en-copyright= kn-copyright= en-aut-name=YamauchiToshihiro en-aut-sei=Yamauchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkaoYohei en-aut-sei=Akao en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshitaniRyota en-aut-sei=Yoshitani en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraYuichi en-aut-sei=Nakamura en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HashimotoMasaki en-aut-sei=Hashimoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University. NTT Communications Corporation kn-affil= affil-num=3 en-affil=raduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Hitachi Ltd. kn-affil= affil-num=5 en-affil=Graduate School of Information Security, Institute of Information Security kn-affil= en-keyword=Privilege escalation attack prevention kn-keyword=Privilege escalation attack prevention en-keyword=Operating system kn-keyword=Operating system en-keyword=Linux kernel vulnerabilities kn-keyword=Linux kernel vulnerabilities en-keyword=Non-control-data attack kn-keyword=Non-control-data attack en-keyword=System security kn-keyword=System security END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=3 article-no= start-page=356 end-page=369 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Japanese guidelines for atopic dermatitis 2020. en-subtitle= kn-subtitle= en-abstract= kn-abstract=Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice. en-copyright= kn-copyright= en-aut-name=KatohNorito en-aut-sei=Katoh en-aut-mei=Norito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhyaYukihiro en-aut-sei=Ohya en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EbiharaTamotsu en-aut-sei=Ebihara en-aut-mei=Tamotsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaIchiro en-aut-sei=Katayama en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaekiHidehisa en-aut-sei=Saeki en-aut-mei=Hidehisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimojoNaoki en-aut-sei=Shimojo en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaAkio en-aut-sei=Tanaka en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakaharaTakeshi en-aut-sei=Nakahara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagaoMizuho en-aut-sei=Nagao en-aut-mei=Mizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HideMichihiro en-aut-sei=Hide en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujitaYuji en-aut-sei=Fujita en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujisawaTakao en-aut-sei=Fujisawa en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FutamuraMasaki en-aut-sei=Futamura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MasudaKoji en-aut-sei=Masuda en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MurotaHiroyuki en-aut-sei=Murota en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Yamamoto-HanadaKiwako en-aut-sei=Yamamoto-Hanada en-aut-mei=Kiwako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science kn-affil= affil-num=2 en-affil=Allergy Center, National Center for Child Health and Development kn-affil= affil-num=3 en-affil=Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Dermatology, Graduate School of Medicine, Osaka University kn-affil= affil-num=6 en-affil=Department of Dermatology, Graduate School of Medicine, Nihon Medical School kn-affil= affil-num=7 en-affil=Department of Pediatrics, Graduate School of Medicine, Chiba University kn-affil= affil-num=8 en-affil=Department of Dermatology, Hiroshima University Graduate School of Biomedical Sciences kn-affil= affil-num=9 en-affil=Division of Skin Surface Sensing, Department of Dermatology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Division of Clinical Research, National Hospital Organization Mie National Hospital kn-affil= affil-num=11 en-affil=Department of Dermatology, Hiroshima University Graduate School of Biomedical Sciences kn-affil= affil-num=12 en-affil=Department of Pediatrics, Graduate School of Medicine, Chiba University kn-affil= affil-num=13 en-affil=Division of Allergy, National Hospital Organization Mie National Hospital kn-affil= affil-num=14 en-affil=Division of Pediatrics, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=15 en-affil=Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science kn-affil= affil-num=16 en-affil=Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=17 en-affil=Allergy Center, National Center for Child Health and Development kn-affil= en-keyword=Atopic dermatitis kn-keyword=Atopic dermatitis en-keyword=Clinical practice guidelines kn-keyword=Clinical practice guidelines en-keyword=Eczema kn-keyword=Eczema en-keyword=Evidence-based medicine kn-keyword=Evidence-based medicine en-keyword=Treatment kn-keyword=Treatment END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=4 article-no= start-page=100998 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200424 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which cytotoxic T lymphocytes (CTLs) are regenerated from iPSCs that were originally derived from T cells and succeeded in regenerating CTLs specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. In this study, we extended our strategy to solid tumors. The regenerated WT1-specific CTLs had a strong therapeutic effect in orthotopic xenograft model using a renal cell carcinoma (RCC) cell line. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specific TCR α/β genes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of RCC, demonstrating the feasibility of our strategy against solid tumors. en-copyright= kn-copyright= en-aut-name=KashimaSoki en-aut-sei=Kashima en-aut-mei=Soki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaTakuya en-aut-sei=Maeda en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MasudaKyoko en-aut-sei=Masuda en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaganoSeiji en-aut-sei=Nagano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueTakamitsu en-aut-sei=Inoue en-aut-mei=Takamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakedaMasashi en-aut-sei=Takeda en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KonoYuka en-aut-sei=Kono en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KobayashiTakashi en-aut-sei=Kobayashi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SaitoShigeyoshi en-aut-sei=Saito en-aut-mei=Shigeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=Ichise Hiroshi en-aut-sei=Ichise en-aut-mei= Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KobayashiYuka en-aut-sei=Kobayashi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IwaisakoKeiko en-aut-sei=Iwaisako en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TeradaKoji en-aut-sei=Terada en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AgataYasutoshi en-aut-sei=Agata en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NumakuraKazuyuki en-aut-sei=Numakura en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SaitoMitsuru en-aut-sei=Saito en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NaritaShintaro en-aut-sei=Narita en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YasukawaMasaki en-aut-sei=Yasukawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OgawaOsamu en-aut-sei=Ogawa en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HabuchiTomonori en-aut-sei=Habuchi en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KawamotoHiroshi en-aut-sei=Kawamoto en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University kn-affil= affil-num=2 en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University kn-affil= affil-num=3 en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University kn-affil= affil-num=4 en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University kn-affil= affil-num=5 en-affil= Department of Urology, Akita University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, Kyoto University Graduate School of Medicine kn-affil= affil-num=7 en-affil= Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University kn-affil= affil-num=8 en-affil=Department of Urology, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Medical Physics and Engineering, Division of Health Sciences, Osaka University kn-affil= affil-num=10 en-affil=Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University kn-affil= affil-num=12 en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University kn-affil= affil-num=13 en-affil=Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University kn-affil= affil-num=14 en-affil=Department of Biochemistry and Molecular Biology, Shiga University of Medical School kn-affil= affil-num=15 en-affil=Department of Biochemistry and Molecular Biology, Shiga University of Medical School kn-affil= affil-num=16 en-affil=Department of Urology, Akita University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Urology, Akita University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Urology, Akita University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University kn-affil= affil-num=20 en-affil=Department of Urology, Kyoto University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Urology, Akita University Graduate School of Medicine kn-affil= affil-num=22 en-affil= Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University kn-affil= en-keyword=Cancer kn-keyword=Cancer en-keyword=Cellular Therapy kn-keyword=Cellular Therapy en-keyword=Immunological Methods kn-keyword=Immunological Methods END start-ver=1.4 cd-journal=joma no-vol=59 cd-vols= no-issue=17 article-no= start-page=1701 end-page=1710 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development and Characterization of Novel Molecular Probes for Ca2+/Calmodulin-Dependent Protein Kinase Kinase, Derived from STO-609 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) activates particular multifunctional kinases, including CaMKI, CaMKIV, and 5′AMP-activated protein kinase (AMPK), resulting in the regulation of various Ca2+-dependent cellular processes, including neuronal, metabolic, and pathophysiological pathways. We developed and characterized a novel pan-CaMKK inhibitor, TIM-063 (2-hydroxy-3-nitro-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) derived from STO-609 (7H-benzimidazo[2,1-a]benz[de]isoquinoline-7-one-3-carboxylic acid), and an inactive analogue (TIM-062) as molecular probes for the analysis of CaMKK-mediated cellular responses. Unlike STO-609, TIM-063 had an inhibitory activity against CaMKK isoforms (CaMKKα and CaMKKβ) with a similar potency (Ki = 0.35 μM for CaMKKα, and Ki = 0.2 μM for CaMKKβ) in vitro. Two TIM-063 analogues lacking a nitro group (TIM-062) or a hydroxy group (TIM-064) completely impaired CaMKK inhibitory activities, indicating that both substituents are necessary for the CaMKK inhibitory activity of TIM-063. Enzymatic analysis revealed that TIM-063 is an ATP-competitive inhibitor that directly targets the catalytic domain of CaMKK, similar to STO-609. TIM-063 suppressed the ionomycin-induced phosphorylation of exogenously expressed CaMKI, CaMKIV, and endogenous AMPKα in HeLa cells with an IC50 of ∼0.3 μM, and it suppressed CaMKK isoform-mediated CaMKIV phosphorylation in transfected COS-7 cells. Thus, TIM-063, but not the inactive analogue (TIM-062), displayed cell permeability and the ability to inhibit CaMKK activity in cells. Taken together, these results indicate that TIM-063 could be a useful tool for the precise analysis of CaMKK-mediated signaling pathways and may be a promising lead compound for the development of therapeutic agents for the treatment of CaMKK-related diseases. en-copyright= kn-copyright= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OzekiYui en-aut-sei=Ozeki en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraMoeno en-aut-sei=Fujiwara en-aut-mei=Moeno kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyagawaTomoyuki en-aut-sei=Miyagawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanayamaKanayamaNaoki en-aut-sei=Kanayama en-aut-mei=KanayamaNaoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=HatanoNaoya en-aut-sei=Hatano en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=IshikawaTeruhiko en-aut-sei=Ishikawa en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Education, Okayama Universit kn-affil= affil-num=4 en-affil= Graduate School of Education, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama Universityayama University kn-affil= affil-num=7 en-affil=Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil= Institute for Genetic Medicine, Hokkaido University kn-affil= affil-num=9 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=525 cd-vols= no-issue=1 article-no= start-page=251 end-page=257 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200423 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phosphorylation and dephosphorylation of Ca2+/calmodulin-dependent protein kinase kinase β at Thr144 in HeLa cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) acts as a regulatory kinase that phosphorylates and activates multiple downstream kinases including CaMKI, CaMKIV, 5′AMP-activated protein kinase (AMPK) and protein kinase B (PKB), resulting in regulation of wide variety of Ca2+-dependent physiological responses under normal and pathological conditions. CaMKKβ is regulated by Ca2+/calmodulin-binding, autophosphorylation, and transphosphorylation by multiple protein kinases including cAMP-dependent protein kinase (PKA). In this report, we found that phosphorylation of CaMKKβ is dynamically regulated by protein phosphatase/kinase system in HeLa cells. Global phosphoproteomic analysis revealed the constitutive phosphorylation at 8 Ser residues including Ser128, 132, and 136 in the N-terminal regulatory domain of rat CaMKKβ in unstimulated HeLa cells as well as inducible phosphorylation of Thr144 in the cells treated with a phosphatase inhibitor, okadaic acid (OA). Thr144 phosphorylation in CaMKKβ has shown to be rapidly induced by OA treatment in a time- and dose-dependent manner in transfected HeLa cells, indicating that Thr144 in CaMKKβ is maintained unphosphorylated state by protein phosphatase(s). We confirmed that in vitro dephosphorylation of pThr144 in CaMKKβ by protein phosphatase 2A and 1. We also found that the pharmacological inhibition of protein phosphatase(s) significantly induces CaMKKβ-phosphorylating activity (at Thr144) in HeLa cell lysates as well as in intact cells; however, it was unlikely that this activity was catalyzed by previously identified Thr144-kinases, such as AMPK and PKA. Taken together, these results suggest that the phosphorylation and dephosphorylation of Thr144 in CaMKKβ is dynamically regulated by multiple kinases/phosphatases signaling resulting in fine-tuning of the enzymatic property. en-copyright= kn-copyright= en-aut-name=TakabatakeShota en-aut-sei=Takabatake en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukumotoYusei en-aut-sei=Fukumoto en-aut-mei=Yusei 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=KanayamaNaoki en-aut-sei=Kanayama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=SakagamiHiroyuki en-aut-sei=Sakagami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HatanoNaoya en-aut-sei=Hatano en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=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=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Anatomy, Kitasato University School of Medicine kn-affil= affil-num=7 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=pplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=CaMKKβ kn-keyword=CaMKKβ en-keyword=Phosphorylation kn-keyword=Phosphorylation en-keyword=Dephosphorylation kn-keyword=Dephosphorylation en-keyword=PP1 kn-keyword=PP1 en-keyword=PP2A kn-keyword=PP2A en-keyword=Okadaic acid kn-keyword=Okadaic acid END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=755 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200319 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cell Stress Induced Stressome Release Including Damaged Membrane Vesicles and Extracellular HSP90 by Prostate Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tumor cells exhibit therapeutic stress resistance-associated secretory phenotype involving extracellular vesicles (EVs) such as oncosomes and heat shock proteins (HSPs). Such a secretory phenotype occurs in response to cell stress and cancer therapeutics. HSPs are stress-responsive molecular chaperones promoting proper protein folding, while also being released from cells with EVs as well as a soluble form known as alarmins. We have here investigated the secretory phenotype of castration-resistant prostate cancer (CRPC) cells using proteome analysis. We have also examined the roles of the key co-chaperone CDC37 in the release of EV proteins including CD9 and epithelial-to-mesenchymal transition (EMT), a key event in tumor progression. EVs derived from CRPC cells promoted EMT in normal prostate epithelial cells. Some HSP family members and their potential receptor CD91/LRP1 were enriched at high levels in CRPC cell-derived EVs among over 700 other protein types found by mass spectrometry. The small EVs (30-200 nm in size) were released even in a non-heated condition from the prostate cancer cells, whereas the EMT-coupled release of EVs (200-500 nm) and damaged membrane vesicles with associated HSP90 alpha was increased after heat shock stress (HSS). GAPDH and lactate dehydrogenase, a marker of membrane leakage/damage, were also found in conditioned media upon HSS. During this stress response, the intracellular chaperone CDC37 was transcriptionally induced by heat shock factor 1 (HSF1), which activated the CDC37 core promoter, containing an interspecies conserved heat shock element. In contrast, knockdown of CDC37 decreased EMT-coupled release of CD9-containing vesicles. Triple siRNA targeting CDC37, HSP90 alpha, and HSP90 beta was required for efficient reduction of this chaperone trio and to reduce tumorigenicity of the CRPC cells in vivo. Taken together, we define "stressome" as cellular stress-induced all secretion products, including EVs (200-500 nm), membrane-damaged vesicles and remnants, and extracellular HSP90 and GAPDH. Our data also indicated that CDC37 is crucial for the release of vesicular proteins and tumor progression in prostate cancer. en-copyright= kn-copyright= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=MatsumotoMasaki en-aut-sei=Matsumoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Manh TienTran en-aut-sei=Manh Tien en-aut-mei=Tran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkushaYuka en-aut-sei=Okusha en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LangBenjamin J. en-aut-sei=Lang en-aut-mei=Benjamin J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University kn-affil= affil-num=5 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=8 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=cell stress response kn-keyword=cell stress response en-keyword=stressome kn-keyword=stressome en-keyword=extracellular vesicle kn-keyword=extracellular vesicle en-keyword=heat shock protein 90 (HSP90) kn-keyword=heat shock protein 90 (HSP90) en-keyword=cell division control 37 (CDC37) kn-keyword=cell division control 37 (CDC37) en-keyword=prostate cancer kn-keyword=prostate cancer en-keyword=exosome kn-keyword=exosome en-keyword=ectosome kn-keyword=ectosome END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=9 article-no= start-page=3441 end-page=3445 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rhenium-Catalyzed Regioselective ortho-Alkenylation and [3 + 2 + 1] Cycloaddition of Phenols with Internal Alkynes en-subtitle= kn-subtitle= en-abstract= kn-abstract=An operationally simple and direct rhenium-catalyzed ortho-alkenylation (C-alkenylation) of unprotected phenols with alkynes was developed. The protocol provided ortho-alkenylphenols exclusively, and formation of para- or multiply alkenylated phenols and hydrophenoxylation (O-alkenylation) products were not observed. The [3 + 2 + 1] cycloaddition of phenols and two alkynes via ortho-alkenylation was also demonstrated, in which the alkynes functioned as both two- and one-carbon units. These reactions proceeded with readily available starting materials under neutral conditions without additional ligands. en-copyright= kn-copyright= en-aut-name=MuraiMasahito en-aut-sei=Murai en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoMasaki en-aut-sei=Yamamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaiKazuhiko en-aut-sei=Takai en-aut-mei=Kazuhiko 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 Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=anti-markovnikov addition kn-keyword=anti-markovnikov addition en-keyword=intramolecular hydroarylation kn-keyword=intramolecular hydroarylation en-keyword=oxidative annulation kn-keyword=oxidative annulation en-keyword=gold kn-keyword=gold en-keyword=hydrophenoxylation kn-keyword=hydrophenoxylation en-keyword=construction kn-keyword=construction en-keyword=cyclization kn-keyword=cyclization en-keyword=vinylation kn-keyword=vinylation en-keyword=alkenes kn-keyword=alkenes END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=66 article-no= start-page=15189 end-page=15197 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190918 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanistic Insights into Rhenium-Catalyzed Regioselective C-Alkenylation of Phenols with Internal Alkynes en-subtitle= kn-subtitle= en-abstract= kn-abstract= A (μ-aryloxo)rhenium complex was isolated and confirmed as a key precatalyst for rhenium-catalyzed ortho-alkenylation (C-alkenylation) of unprotected phenols with alkynes. The reaction exclusively provided ortho-alkenylphenols; the formation of para or multiply alkenylated phenols and hydrophenoxylation (O-alkenylation) products was not observed. Several mechanistic experiments excluded a classical Friedel-Crafts-type mechanism, leading to the proposed phenolic hydroxyl group assisted electrophilic alkenylation as the most plausible reaction mechanism. For this purpose, the use of rhenium, a metal between the early and late transition metals in the periodic table, was key for the activation of both the soft carbon-carbon triple bond of the alkyne and the hard oxygen atom of the phenol, at the same time. ortho-Selective alkenylation with allenes also provided the corresponding adducts with a substitution pattern different from that obtained by the addition reaction with alkynes. en-copyright= kn-copyright= en-aut-name=MuraiMasahito en-aut-sei=Murai en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoMasaki en-aut-sei=Yamamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaiKazuhiko en-aut-sei=Takai en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=alkenylation kn-keyword=alkenylation en-keyword=homogeneous catalysis kn-keyword=homogeneous catalysis en-keyword=reaction mechanisms kn-keyword=reaction mechanisms en-keyword=regioselectivity kn-keyword=regioselectivity en-keyword=rhenium kn-keyword=rhenium END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=4159 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ultrafast isomerization-induced cooperative motions to higher molecular orientation in smectic liquid-crystalline azobenzene molecules en-subtitle= kn-subtitle= en-abstract= kn-abstract=The photoisomerization of molecules is widely used to control the structure of soft matter in both natural and synthetic systems. However, the structural dynamics of the molecules during isomerization and their subsequent response are difficult to elucidate due to their complex and ultrafast nature. Herein, we describe the ultrafast formation of higherorientation of liquid-crystalline (LC) azobenzene molecules via linearly polarized ultraviolet light (UV) using ultrafast time-resolved electron diffraction. The ultrafast orientation is caused by the trans-to-cis isomerization of the azobenzene molecules. Our observations are consistent with simplified molecular dynamics calculations that revealed that the molecules are aligned with the laser polarization axis by their cooperative motion after photoisomerization. This insight advances the fundamental chemistry of photoresponsive molecules in soft matter as well as their ultrafast photomechanical applications. en-copyright= kn-copyright= en-aut-name=HadaMasaki en-aut-sei=Hada en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaguchiDaisuke en-aut-sei=Yamaguchi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshikawaTadahiko en-aut-sei=Ishikawa en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SawaTakayoshi en-aut-sei=Sawa en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsurutaKenji en-aut-sei=Tsuruta en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshikawaKen en-aut-sei=Ishikawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KoshiharaShin-Ya en-aut-sei=Koshihara en-aut-mei=Shin-Ya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HayashiYasuhiko en-aut-sei=Hayashi en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatoTakashi en-aut-sei=Kato en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry & Biotechnology, School of Engineering, The University of Tokyo kn-affil= affil-num=3 en-affil=School of Science,Tokyo Institute of Technology kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=School of Materials and Chemical Technology, Tokyo Institute of Technology kn-affil= affil-num=7 en-affil=School of Science,Tokyo Institute of Technology kn-affil= affil-num=8 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Department of Chemistry & Biotechnology, School of Engineering, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=366 cd-vols= no-issue=6463 article-no= start-page=334 end-page=338 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191018 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An oxyl/oxo mechanism for dioxygen bond formation in PSII revealed by X-ray free electron lasers en-subtitle= kn-subtitle= en-abstract= kn-abstract= Photosynthetic water oxidation is catalyzed by the Mn4CaO5 cluster of photosystem II (PSII) with linear progression through five S-state intermediates (S0 to S4). To reveal the mechanism of water oxidation, we analyzed structures of PSII in the S1, S2, and S3 states by x-ray free-electron laser serial crystallography. No insertion of water was found in S2, but flipping of D1 Glu189 upon transition to S3 leads to the opening of a water channel and provides a space for incorporation of an additional oxygen ligand, resulting in an open cubane Mn4CaO6 cluster with an oxyl/oxo bridge. Structural changes of PSII between the different S states reveal cooperative action of substrate water access, proton release, and dioxygen formation in photosynthetic water oxidation. en-copyright= kn-copyright= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkitaFusamichi en-aut-sei=Akita en-aut-mei=Fusamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaKeitaro en-aut-sei=Yamashita en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UenoGo en-aut-sei=Ueno en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LiHongjie en-aut-sei=Li en-aut-mei=Hongjie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamaneTakahiro en-aut-sei=Yamane en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirataKunio en-aut-sei=Hirata en-aut-mei=Kunio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UmenaYasufumi en-aut-sei=Umena en-aut-mei=Yasufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YonekuraShinichiro en-aut-sei=Yonekura en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YuLong-Jiang en-aut-sei=Yu en-aut-mei=Long-Jiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MurakamiHironori en-aut-sei=Murakami en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NomuraTakashi en-aut-sei=Nomura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KimuraTetsunari en-aut-sei=Kimura en-aut-mei=Tetsunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KuboMinoru en-aut-sei=Kubo en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=BabaSeiki en-aut-sei=Baba en-aut-mei=Seiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KumasakaTakashi en-aut-sei=Kumasaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TonoKensuke en-aut-sei=Tono en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YabashiMakina en-aut-sei=Yabashi en-aut-mei=Makina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IsobeHiroshi en-aut-sei=Isobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamaguchiKizashi en-aut-sei=Yamaguchi en-aut-mei=Kizashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YamamotoMasaki en-aut-sei=Yamamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=AgoHideo en-aut-sei=Ago en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 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=24 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=12 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=13 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=14 en-affil=Department of Chemistry, Graduate School of Science, Kobe University kn-affil= affil-num=15 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=16 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=17 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=18 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=19 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=20 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=21 en-affil=The Institute for Scientific and Industrial Research, Osaka University kn-affil= affil-num=22 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=23 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=24 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=97 cd-vols= no-issue=6 article-no= start-page=934 end-page=944 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=20100422 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Preoperative estimation of remnant hepatic function by fusion images of CT scans and single photon emission CT (SPECT) using 99mTc-GSA. en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND:
Assessment of hepatic functional reserve is important in hepatic resection. The aim of this study was to evaluate the role of hepatic asialoglycoprotein receptor (ASGP-R) analysis in the preoperative estimation of remnant liver function in liver surgery.
METHODS:
One hundred and one patients undergoing hepatic resection for liver tumours were studied. Seventeen patients had preoperative percutaneous transhepatic portal vein embolization (PTPE). Function of the hepatic remnant was estimated before surgery using radioactivity in fusion images of both liver single-photon emission computed tomography and computed tomography scans using (99m)Tc-labelled diethylene triamine penta-acetate-galactosyl-human serum albumin.
RESULTS:
All three patients with an ASGP-R concentration below 400 nmol/l and preoperative total amount of receptor in the future remnant liver (R0-remnant) of less than 53.0 nmol per liver died. Two patients with chronic hepatitis and R0-remnant values between 53.0 and 65.0 nmol per liver and a receptor concentration lower than 600 nmol/l developed liver dysfunction. The incidence of liver failure decreased inversely with increasing R0-remnant value.
CONCLUSION:
A combination of receptor concentration and the amount of hepatic receptor in the future liver remnant as detected on fusion images is useful in evaluating the risk of postoperative liver failure. en-copyright= kn-copyright= en-aut-name=YumotoYasuhiro en-aut-sei=Yumoto en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Sato Shuhei en-aut-sei=Sato en-aut-mei= Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiYoshiyuki en-aut-sei=Kobayashi en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhmotoMasaki en-aut-sei=Ohmoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YumotoEiichiro en-aut-sei=Yumoto en-aut-mei=Eiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagayaIsao en-aut-sei=Nagaya en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakatsukasaHarushige en-aut-sei=Nakatsukasa en-aut-mei=Harushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Radioisotope Centre, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Saiseikai Imabari Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=hepatic resection kn-keyword=hepatic resection en-keyword=remnant hepatic function kn-keyword=remnant hepatic function en-keyword=fusion image of SPECT and X-ray CT kn-keyword=fusion image of SPECT and X-ray CT END start-ver=1.4 cd-journal=joma no-vol=519 cd-vols= no-issue=2 article-no= start-page=309 end-page=315 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Jiadifenolide induces the expression of cellular communication network factor (CCN) genes, and CCN2 exhibits neurotrophic activity in neuronal precursor cells derived from human induced pluripotent stem cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= Jiadifenolide has been reported to have neurotrophin-like activity in primary rat cortical neurons, and also possesses neurotrophic effects in neuronal precursor cells derived from human induced pluripotent stem cells (hiPSCs), as we have previously reported. However, the molecular mechanisms by which jiadifenolide exerts its neurotrophic effects in rat and human neurons are unknown. Thus, we aimed to investigate the molecular mechanisms and pathways by which jiadifenolide promotes neurotrophic effects. Here, we found that jiadifenolide activated cellular communication network factor (CCN) signaling pathways by up-regulating mRNA level expression of CCN genes in human neuronal cells. We also found that CCN2 (also known as connective tissue growth factor, CTGF) protein promotes neurotrophic effects through activation of the p44/42 mitogen-activated protein kinase signaling pathway. This is the first discovery which links neurotrophic activity with CCN signaling. en-copyright= kn-copyright= en-aut-name=ShojiMasaki en-aut-sei=Shoji en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaMasako en-aut-sei=Ueda en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiokaMegumi en-aut-sei=Nishioka en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MinatoHiroki en-aut-sei=Minato en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SekiMasahide en-aut-sei=Seki en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaradaKenichi en-aut-sei=Harada en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KuboMiwa en-aut-sei=Kubo en-aut-mei=Miwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukuyamaYoshiyasu en-aut-sei=Fukuyama en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiYutaka en-aut-sei=Suzuki en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AoyamaEriko en-aut-sei=Aoyama en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KuzuharaTakashi en-aut-sei=Kuzuhara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University kn-affil= affil-num=2 en-affil=Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University kn-affil= affil-num=3 en-affil=Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University kn-affil= affil-num=4 en-affil=Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Laboratory of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University kn-affil= affil-num=7 en-affil=Laboratory of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University kn-affil= affil-num=8 en-affil=Laboratory of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University kn-affil= affil-num=9 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo kn-affil= affil-num=10 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School/Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School/Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University kn-affil= en-keyword=CCN signaling pathway kn-keyword=CCN signaling pathway en-keyword=CCN2 kn-keyword=CCN2 en-keyword=Jiadifenolide kn-keyword=Jiadifenolide en-keyword=Neurotrophin kn-keyword=Neurotrophin en-keyword=iPS kn-keyword=iPS END start-ver=1.4 cd-journal=joma no-vol=1863 cd-vols= no-issue=4 article-no= start-page=672 end-page=680 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190117 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Regulation of Ca2+/calmodulin-dependent protein kinase kinase beta by cAMP signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND:
Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) is a pivotal activator of CaMKI, CaMKIV and 5'-AMP-activated protein kinase (AMPK), controlling Ca2+-dependent intracellular signaling including various neuronal, metabolic and pathophysiological responses. Recently, we demonstrated that CaMKKβ is feedback phosphorylated at Thr144 by the downstream AMPK, resulting in the conversion of CaMKKβ into Ca2+/CaM-dependent enzyme. However, the regulatory phosphorylation of CaMKKβ at Thr144 in intact cells and in vivo remains unclear.
METHODS:
Anti-phosphoThr144 antibody was used to characterize the site-specific phosphorylation of CaMKKβ in immunoprecipitated samples from mouse cerebellum and in transfected mammalian cells that were treated with various agonists and protein kinase inhibitors. CaMKK activity assay and LC-MS/MS analysis were used for biochemical characterization of phosphorylated CaMKKβ.
RESULTS:
Our data suggest that the phosphorylation of Thr144 in CaMKKβ is rapidly induced by cAMP/cAMP-dependent protein kinase (PKA) signaling in CaMKKβ-transfected HeLa cells, that is physiologically relevant in mouse cerebellum. We confirmed that the catalytic subunit of PKA was capable of directly phosphorylating CaMKKβ at Thr144 in vitro and in transfected cells. In addition, the basal phosphorylation of CaMKKβ at Thr144 in transfected HeLa cells was suppressed by AMPK inhibitor (compound C). PKA-catalyzed phosphorylation reduced the autonomous activity of CaMKKβ in vitro without significant effect on the Ca2+/CaM-dependent activity, resulting in the conversion of CaMKKβ into Ca2+/CaM-dependent enzyme.
CONCLUSION:
cAMP/PKA signaling may confer Ca2+-dependency to the CaMKKβ-mediated signaling pathway through direct phosphorylation of Thr144 in intact cells.
GENERAL SIGNIFICANCE:
Our results suggest a novel cross-talk between cAMP/PKA and Ca2+/CaM/CaMKKβ signaling through regulatory phosphorylation. en-copyright= kn-copyright= en-aut-name=TakabatakeShota en-aut-sei=Takabatake en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugawaraTakeyuki en-aut-sei=Sugawara en-aut-mei=Takeyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HatanoNaoya en-aut-sei=Hatano en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanayamaNaoki en-aut-sei=Kanayama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=SakagamiHiroyuki en-aut-sei=Sakagami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Anatomy, Kitasato University School of Medicine 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=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Anatomy, Kitasato University School of Medicine kn-affil= affil-num=8 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=CaMKK kn-keyword=CaMKK en-keyword=Calmodulin kn-keyword=Calmodulin en-keyword=Intracellular Ca(2+) kn-keyword=Intracellular Ca(2+) en-keyword=PKA kn-keyword=PKA en-keyword=Phosphorylation kn-keyword=Phosphorylation en-keyword=Signal transduction kn-keyword=Signal transduction END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=19 article-no= start-page=8809 end-page=8818 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Competitive Binding Assay with an Umbelliferone-Based Fluorescent Rexinoid for Retinoid X Receptor Ligand Screening en-subtitle= kn-subtitle= en-abstract= kn-abstract= Ligands for retinoid X receptors (RXRs), "rexinoids", are attracting interest as candidates for therapy of type 2 diabetes and Alzheimer's and Parkinson's diseases. However, current screening methods for rexinoids are slow and require special apparatus or facilities. Here, we created 7-hydroxy-2-oxo-6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2H-chromene-3-carboxylic acid (10, CU-6PMN) as a new fluorescent RXR agonist and developed a screening system of rexinoids using 10. Compound 10 was designed based on the fact that umbelliferone emits strong fluorescence in a hydrophilic environment, but the fluorescence intensity decreases in hydrophobic environments such as the interior of proteins. The developed assay using 10 enabled screening of rexinoids to be performed easily within a few hours by monitoring changes of fluorescence intensity with widely available fluorescence microplate readers, without the need for processes such as filtration. en-copyright= kn-copyright= en-aut-name=YamadaShoya en-aut-sei=Yamada en-aut-mei=Shoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawasakiMayu en-aut-sei=Kawasaki en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiharaMichiko en-aut-sei=Fujihara en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeMasaki en-aut-sei=Watanabe en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakamuraYuta en-aut-sei=Takamura en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakiokuMaho en-aut-sei=Takioku en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiokaHiromi en-aut-sei=Nishioka en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiYasuo en-aut-sei=Takeuchi en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MakishimaMakoto en-aut-sei=Makishima en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MotoyamaTomoharu en-aut-sei=Motoyama en-aut-mei=Tomoharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ItoSohei en-aut-sei=Ito en-aut-mei=Sohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TokiwaHiroaki en-aut-sei=Tokiwa en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakanoShogo en-aut-sei=Nakano en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KakutaHiroki en-aut-sei=Kakuta en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil= kn-affil= affil-num=3 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine kn-affil= affil-num=10 en-affil=Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka kn-affil= affil-num=11 en-affil=Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka kn-affil= affil-num=12 en-affil=Department of Chemistry and Research Center of Smart Molecules, Rikkyo University kn-affil= affil-num=13 en-affil=Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka kn-affil= affil-num=14 en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=5 article-no= start-page=1362 end-page=1369 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190730 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genome-Edited Triple-Recessive Mutation AltersSeed Dormancy in Wheat en-subtitle= kn-subtitle= en-abstract= kn-abstract=1Common wheat has three sets of sub-genomes, making mutations difficult to observe, especially for traits controlled by recessive genes. Here, we produced hexaploid wheat lines with loss of function of homeoalleles of Qsd1, which controls seed dormancy in barley, by Agrobacterium-mediated CRISPR/Cas9. Of the eight transformed wheat events produced, three independent events carrying multiple mutations in wheat Qsd1 homeoalleles were obtained. Notably, one line had mutations in every homeoallele. We crossed this plant with wild-type cultivar Fielder to generate a transgene-free triple-recessive mutant, as revealed by Mendelian segregation. The mutant showed a significantly longer seed dormancy period than wild-type, which may result in reduced pre-harvest sprouting of grains on spikes. PCR, southern blotting, and whole-genome shotgun sequencing revealed that this segregant lacked transgenes in its genomic sequence. This technique serves as a model for trait improvement in wheat, particularly for genetically recessive traits, based on locus information from diploid barley. en-copyright= kn-copyright= en-aut-name=AbeFumitaka en-aut-sei=Abe en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaqueEmdadul en-aut-sei=Haque en-aut-mei=Emdadul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTsuyoshi en-aut-sei=Tanaka en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamiyaYoko en-aut-sei=Kamiya en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MikamiMasafumi en-aut-sei=Mikami en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawauraKanako en-aut-sei=Kawaura en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EndoMasaki en-aut-sei=Endo en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OnishiKazumitsu en-aut-sei=Onishi en-aut-mei=Kazumitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HayashiTakeshi en-aut-sei=Hayashi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Division of Wheat and Barley Research, Institute of Crop Science, NARO kn-affil= affil-num=2 en-affil=Division of Wheat and Barley Research, Institute of Crop Science, NARO kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Division of Basic Research, Institute of Crop Science, NARO kn-affil= affil-num=5 en-affil=Kihara Institute for Biological Research, Yokohama City University kn-affil= affil-num=6 en-affil=Graduate School of Nanobioscience, Yokohama City University kn-affil= affil-num=7 en-affil=Kihara Institute for Biological Research, Yokohama City University kn-affil= affil-num=8 en-affil=Division of Applied Genetics, Institute of Agrobiological Sciences, NARO kn-affil= affil-num=9 en-affil=Department of Agro-Environmental Science, Obihiro University of Agriculture and Veterinary Medicine kn-affil= affil-num=10 en-affil=Division of Basic Research, Institute of Crop Science, NARO kn-affil= affil-num=11 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=Qsd1 kn-keyword=Qsd1 en-keyword=multiple mutation kn-keyword=multiple mutation en-keyword=seed dormancy kn-keyword=seed dormancy en-keyword=wheat kn-keyword=wheat END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=5 article-no= start-page=469 end-page=474 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phase II Trial Using Romidepsin after Gemcitabine, Dexamethasone, and Cisplatin Therapy in Elderly Transplant-Ineligible Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma: Study Protocol en-subtitle= kn-subtitle= en-abstract= kn-abstract= Romidepsin is an important therapeutic option for patients with peripheral T-cell lymphoma (PTCL). However, the timing of romidepsin administration remains controversial. Romidepsin was launched in Japan as a consolidation therapy agent after conventional salvage chemotherapy with gemcitabine, dexamethasone, and cisplatin (GDP). GDP therapy will be administered every 3 weeks. If complete response, partial response, or stable disease is confirmed after 2-4 GDP cycles, romidepsin will be administered every 4 weeks. The primary endpoint is a 2-year progression-free survival rate. Patients participating in this study and undergoing treatment can expect results similar to or better than those of conventional therapies. en-copyright= kn-copyright= en-aut-name=YamasakiSatoshi en-aut-sei=Yamasaki en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KadaAkiko en-aut-sei=Kada en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaiHirokazu en-aut-sei=Nagai en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaIsao en-aut-sei=Yoshida en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChoiIlseung en-aut-sei=Choi en-aut-mei=Ilseung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaitoAkiko M. en-aut-sei=Saito en-aut-mei=Akiko M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwasakiaHiromi en-aut-sei=Iwasakia en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Hematology and Clinical Research Institute, NHO Kyushu Medical Cente kn-affil= affil-num=2 en-affil=Department of Clinical Trials and Research, Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=3 en-affil=Department ofHematology and Oncology Research, NHO Nagoya Medical Center kn-affil= affil-num=4 en-affil=Department of Hematologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Hematology, NHO Kyushu Cancer Center kn-affil= affil-num=6 en-affil=Department of Clinical Trials and Research, Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=7 en-affil=Department of Hematology and Clinical Research Institute, NHO Kyushu Medical Cente kn-affil= en-keyword=peripheral T-cell lymphoma not otherwise specified kn-keyword=peripheral T-cell lymphoma not otherwise specified en-keyword=angioimmunoblastic T-cell lymphoma kn-keyword=angioimmunoblastic T-cell lymphoma en-keyword=gemcitabine kn-keyword=gemcitabine en-keyword=cisplatin, romidepsin kn-keyword=cisplatin, romidepsin END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=5 article-no= start-page=457 end-page=461 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Granulation Polyp in the Colon Masquerading as Metastatic Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= A 60-year-old Caucasian male was diagnosed with lung adenocarcinoma and multiple metastases to the bone, spleen, and brain. He underwent radiotherapy for the brain and lumbar spine metastases, plus chemotherapy (cisplatin and pemetrexed). The chemotherapy was discontinued due to vomiting and hyponatremia, and nivolumab was then administered. Eight months later, 18F-fluorodeoxyglucose positron emission tomography showed tracer uptake in the colon. Colonoscopy revealed a reddish multinodular polyp in the sigmoid colon. The polyp showed irregular microvessels. No colonic mucosal surface structures were observed. Colonic metastasis of the lung carcinoma was highly suspected; the polyp was therefore surgically removed. The histological analysis revealed granulation tissue and suppurative inflammation without neoplastic changes. We diagnosed the lesion as a granulation polyp. Despite the difficulty in diagnosing these lesions due to their rarity and similarity to metastatic colon tumors, we suggest that recognizing the endoscopic features of the polyp surface may allow a preoperative diagnosis. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=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=YamazakiTatsuhiro en-aut-sei=Yamazaki en-aut-mei=Tatsuhiro 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=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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 General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=colonoscopy kn-keyword=colonoscopy en-keyword=colonic neoplasms kn-keyword=colonic neoplasms en-keyword=granulation polyp kn-keyword=granulation polyp END start-ver=1.4 cd-journal=joma no-vol=156 cd-vols= no-issue=6 article-no= start-page=1753 end-page=1760 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND & AIMS:
Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of post-ERCP pancreatitis (PEP). Little is known about the combined effects of sublingual nitrate and NSAIDs. We performed a randomized trial to assess whether the combination of NSAIDs and sublingual nitrate is more effective than NSAIDs alone in preventing PEP.
METHODS:
In a prospective superiority trial, eligible patients underwent ERCP at 12 endoscopic units in Japan, from March 2015 through May 2018. Patients were randomly assigned to groups given diclofenac suppositories (50 mg) within 15 minutes after the endoscopic procedure alone (diclofenac-alone group, n = 442) or in combination with sublingual isosorbide dinitrate (5 mg) 5 minutes before the endoscopic procedure (combination group, n = 444). The primary endpoint was the occurrence of PEP.
RESULTS:
PEP developed in 25 patients in the combination group (5.6%), and in 42 patients in the diclofenac-alone group (9.5%) (relative risk 0.59; 95% confidence interval 0.37-0.95; P = .03). Moderate to severe pancreatitis developed in 4 patients (0.9%) in the combination group, and 10 patients (2.3%) in the diclofenac-alone group (relative risk 0.12; 95% confidence interval 0.13-1.26; P = .12). There was no serious adverse event related to the additional administration of sublingual nitrate.
CONCLUSIONS:
In a randomized controlled trial, we found that prophylaxis with rectal diclofenac and sublingual nitrate significantly reduces the overall incidence of PEP compared with diclofenac suppository alone. ClinicalTrials.gov, no: UMIN 000016274. en-copyright= kn-copyright= en-aut-name=TomodaTakeshi en-aut-sei=Tomoda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UekiToru en-aut-sei=Ueki en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkimotoYutaka en-aut-sei=Akimoto en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HataHidenori en-aut-sei=Hata en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiMasakuni en-aut-sei=Fujii en-aut-mei=Masakuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Harada Ryo en-aut-sei=Harada en-aut-mei= Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OgawaTsuneyoshi en-aut-sei=Ogawa en-aut-mei=Tsuneyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Wato Masaki en-aut-sei=Wato en-aut-mei= Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakataniMasahiro en-aut-sei=Takatani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsubaraMinoru en-aut-sei=Matsubara en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawaiYoshinari en-aut-sei=Kawai en-aut-mei=Yoshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=epartment 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 HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Iwakuni Clinical Center kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Mitoyo General Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=8 en-affil=Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=11 en-affil=Department of Internal Medicine, Sumitomo Besshi Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterology, Onomichi Municipal Hospital kn-affil= affil-num=13 en-affil=epartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Drug kn-keyword=Drug en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Pancreas kn-keyword=Pancreas en-keyword=Smooth-Muscle Relaxant kn-keyword=Smooth-Muscle Relaxant END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=2 article-no= start-page=109 end-page=115 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinicopathological Features and Outcomes of Endoscopic Submucosal Dissection for Superficial Cancer of the Pharynx en-subtitle= kn-subtitle= en-abstract= kn-abstract= The efficacy and safety of endoscopic submucosal dissection (ESD) for superficial cancer of the pharynx are still unclear. To identify clinicopathological features of superficial pharyngeal cancer, and the efficacy and safety of ESD, we retrospectively assessed 70 pharyngeal cancers in 59 patients who underwent ESD. Of these patients, 61.0% and 50.8% had a history of esophageal cancer and head and neck cancer, respectively. The median tumor size was 15 mm, and 75.7% of the lesions were located at the piriform sinus. The en bloc resection rate was 94.9%. Treatment-related adverse events occurred in 8 cases, but there was no treatment-related death. The lateral margin was positive for neoplasm in 3 lesions (4.3%) and inconclusive in 27 lesions (38.6%), but no local recurrence was observed. Cervical lymph node metastasis was observed in 6 patients, and was successfully treated by cervical lymph node dissection. The three-year overall survival rate was 91.5% (95%CI: 76.6-97.3%) and the cause-specific survival rate was 97.6% (95%CI: 84.9-99.7%). In conclusion, ESD for superficial pharyngeal cancer was safe and effective. “Resect and watch” is probably a feasible and rational strategy for treatment of patients with superficial pharyngeal cancer. en-copyright= kn-copyright= en-aut-name=AbeMakoto en-aut-sei=Abe en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=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=Kawahara Yoshiro en-aut-sei=Kawahara en-aut-mei= Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanzakiHiromitsu en-aut-sei=Kanzaki en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsumuraMunechika en-aut-sei=Tsumura en-aut-mei=Munechika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NodaYohei en-aut-sei=Noda en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MarunakaHidenori en-aut-sei=Marunaka en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishizakiKazunori en-aut-sei=Nishizaki en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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 Endoscopy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil= Department of Pathology, Okayama University Hospital 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= affil-num=8 en-affil=Department of Otolaryngology-Head and Neck Surgery, 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 Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=endoscopic submucosal dissection kn-keyword=endoscopic submucosal dissection en-keyword=superficial cancer kn-keyword=superficial cancer en-keyword=pharynx kn-keyword=pharynx en-keyword=endoscopic resection kn-keyword=endoscopic resection END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue= article-no= start-page=25 end-page=39 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201903 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Data on the Present Status and Future of Public Transportation Traffic from the Perspective of Information Service and Open Data kn-title=情報提供サービスとオープンデータから視た交通 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ItoMasaki en-aut-sei=Ito en-aut-mei=Masaki kn-aut-name=伊藤昌毅 kn-aut-sei=伊藤 kn-aut-mei=昌毅 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=東京大学生産技術研究所 END start-ver=1.4 cd-journal=joma no-vol=130 cd-vols= no-issue=2 article-no= start-page=55 end-page=56 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20180801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2017 Incentive Award of the Okayama Medical Association in Cancer Research (2017 Hayashibara Prize and Yamada Prize) kn-title=平成29年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name=藤原雅樹 kn-aut-sei=藤原 kn-aut-mei=雅樹 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil=岡山大学病院　精神科神経科 END start-ver=1.4 cd-journal=joma no-vol=72 cd-vols= no-issue=5 article-no= start-page=519 end-page=523 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=201810 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recurrent Meningitis in an 11-year-old Girl with a Petrous Apex Cystic Lesion en-subtitle= kn-subtitle= en-abstract= kn-abstract= Cases of recurrent meningitis in elderly patients with a spontaneous cerebrospinal fistula have been reported, and in some of these patients, cystic lesions were thought to be the underlying cause. We report a case of recurrent meningitis in an 11-year-old Japanese girl with an arachnoid cyst in the petrous apex. Pulsation of the cystic lesion was thought to cause bone erosion, leading to the formation of a fistula. Magnetic resonance imaging was useful in evaluating the arachnoid cyst and fistula. During 2 years of follow-up, the osteolytic lesion enlarged and the rate of bone erosion was higher than expected. en-copyright= kn-copyright= en-aut-name=MiyaharaHiroyuki en-aut-sei=Miyahara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TokumasuHironobu en-aut-sei=Tokumasu en-aut-mei=Hironobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChinMasaki en-aut-sei=Chin en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WakiKenji en-aut-sei=Waki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ArakakiYoshio en-aut-sei=Arakaki en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Clinical Research Support Center, Kurashiki Central Hospital kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Kurashiki Central Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kurashiki Central Hospital kn-affil= en-keyword=magnetic resonance imaging kn-keyword=magnetic resonance imaging en-keyword=pulsation of cystic lesion kn-keyword=pulsation of cystic lesion en-keyword=bone erosion kn-keyword=bone erosion en-keyword=fistula kn-keyword=fistula 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=2018 dt-pub=20180323 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=重度の心理的苦痛とがん検診未受診の関連及び社会経済的要因の修飾効果 : 国民生活基礎調査匿名データによる横断研究 kn-title=Association Between Serious Psychological Distress and Nonparticipation in Cancer Screening and the Modifying Effect of Socioeconomic Status: Analysis of Anonymized Data From a National Cross-Sectional Survey in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name=藤原雅樹 kn-aut-sei=藤原 kn-aut-mei=雅樹 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=2 article-no= start-page=125 end-page=126 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20180226 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Professor Masaki Hirano＇s Brief Biography and List of Publications kn-title=平野正樹教授略歴・研究業績 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=岡山大学経済学会 kn-aut-sei=岡山大学経済学会 kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=95 cd-vols= no-issue=8 article-no= start-page=085109 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=201702 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ce 4f electronic states of CeO1-xFxBiS2 studied by soft x-ray photoemission spectroscopy en-subtitle= kn-subtitle= en-abstract= kn-abstract= We use soft x-ray photoemission spectroscopy (SXPES) to investigate Ce 4f electronic states of a new BiS2 layered superconductor CeO1-xFxBiS2, for polycrystalline and single-crystal samples. The Ce 3d spectrum of the single crystal of nominal composition x = 0.7 has no f(0) component and the spectral shape closely resembles the ones observed for Ce trivalent insulating compounds, strongly implying that the CeO layer is still in an insulating state even after the F doping. The Ce 3d-4f resonant SXPES for both polycrystalline and single-crystal samples shows that the prominent peak is located around 1 eV below the Fermi level (E-F) with negligible spectral intensity at EF. The F-concentration dependence of the valence band spectra for single crystals shows the increases of the degeneracy in energy levels and of the interaction between Ce 4f and S 3p states. These results give insight into the nature of the CeO1-xFx layer and the microscopic coexistence of magnetism and superconductivity in CeO1-xFxBiS2. en-copyright= kn-copyright= en-aut-name=WakitaTakanori en-aut-sei=Wakita en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TerashimaKensei en-aut-sei=Terashima en-aut-mei=Kensei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaTakahiro en-aut-sei=Hamada en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraHirokazu en-aut-sei=Fujiwara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MinoharaMakoto en-aut-sei=Minohara en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiMasaki en-aut-sei=Kobayashi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HoribaKoji en-aut-sei=Horiba en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KumigashiraHiroshi en-aut-sei=Kumigashira en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KutlukGalif en-aut-sei=Kutluk en-aut-mei=Galif kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagaoMasanori en-aut-sei=Nagao en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WatauchiSatoshi en-aut-sei=Watauchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TanakaIsao en-aut-sei=Tanaka en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=DemuraSatoshi en-aut-sei=Demura en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkazakiHiroyuki en-aut-sei=Okazaki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakanoYoshihiko en-aut-sei=Takano en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MizuguchiYoshikazu en-aut-sei=Mizuguchi en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MiuraOsuke en-aut-sei=Miura en-aut-mei=Osuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OkadaKozo en-aut-sei=Okada en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MuraokaYuji en-aut-sei=Muraoka en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YokoyaTakayoshi en-aut-sei=Yokoya en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Research Laboratory for Surface Science and the Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Laboratory for Surface Science and the Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Research Laboratory for Surface Science and the Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Research Laboratory for Surface Science and the Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=6 en-affil=Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=7 en-affil= kn-affil= affil-num=8 en-affil=Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=9 en-affil=Synchrotron Radiation Center, Hiroshima University kn-affil= affil-num=10 en-affil=Center for Crystal Science and Technology, University of Yamanashi kn-affil= affil-num=11 en-affil=Center for Crystal Science and Technology, University of Yamanashi kn-affil= affil-num=12 en-affil=Center for Crystal Science and Technology, University of Yamanashi kn-affil= affil-num=13 en-affil=National Institute for Materials Science kn-affil= affil-num=14 en-affil=National Institute for Materials Science kn-affil= affil-num=15 en-affil=National Institute for Materials Science kn-affil= affil-num=16 en-affil=Department of Electrical and Electronic Engineering, Tokyo Metropolitan University kn-affil= affil-num=17 en-affil=Department of Electrical and Electronic Engineering, Tokyo Metropolitan University kn-affil= affil-num=18 en-affil=Department of Physics and the Graduate school of Natural Science and Technology, Okayama University kn-affil= affil-num=19 en-affil=Research Laboratory for Surface Science and the Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=20 en-affil=Research Laboratory for Surface Science and the Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=9 article-no= start-page=1046 end-page=1049 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=201709 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with cutaneous angiosarcoma: A retrospective study of 18 cases en-subtitle= kn-subtitle= en-abstract= kn-abstract= Cutaneous angiosarcoma (CAS) is a rare soft tissue sarcoma with rapid growth and poor prognosis. We retrospectively analyzed the data of 18 patients with CAS who underwent 18 F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) at the initial visit to the Department of Dermatology, Okayama University Hospital from September 2006 to March 2016. In the univariate survival analysis, patients with high standardized uptake values (SUVmax ) of the primary tumor showed significantly poorer prognosis than those with low SUVmax . Early assessment of prognosis using PET/CT may predict patient survival and is useful in the selection of therapeutic strategies. en-copyright= kn-copyright= en-aut-name=UmemuraHiroshi en-aut-sei=Umemura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KajiTatsuya en-aut-sei=Kaji en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamadaToshihisa en-aut-sei=Hamada en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaMasaki en-aut-sei=Otsuka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsagoeKenji en-aut-sei=Asagoe en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil= Division of Dermatology, Shizuoka Cancer Center Hospital kn-affil= affil-num=6 en-affil= Department of Dermatology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=angiosarcoma kn-keyword=angiosarcoma en-keyword=maximum standardized uptake value kn-keyword=maximum standardized uptake value en-keyword=positron emission tomography kn-keyword=positron emission tomography en-keyword=positron emission tomography/computed tomography kn-keyword=positron emission tomography/computed tomography en-keyword=prognostic factor kn-keyword=prognostic factor END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=5 article-no= start-page=730 end-page=737 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of severity classification in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=OBJECTIVE: To compare disease severity classification systems for six-month outcome prediction in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Patients with newly diagnosed AAV from 53 tertiary institutions were enrolled. Six-month remission, overall survival, and end-stage renal disease (ESRD)-free survival were evaluated. RESULTS: According to the European Vasculitis Study Group (EUVAS)-defined disease severity, the 321 enrolled patients were classified as follows: 14, localized; 71, early systemic; 170, generalized; and 66, severe disease. According to the rapidly progressive glomerulonephritis (RPGN) clinical grading system, the patients were divided as follows: 60, grade I; 178, grade II; 66, grade III; and 12, grade IV. According to the Five-Factor Score (FFS) 2009, 103, 109, and 109 patients had ≤1, 2, and ≥3 points, respectively. No significant difference in remission rates was found in any severity classification. The overall and ESRD-free survival rates significantly differed between grades I/II, III, and IV, regardless of renal involvement. Severe disease was a good predictor of six-month overall and ESRD-free survival. The FFS 2009 was useful to predict six-month ESRD-free survival but not overall survival. CONCLUSIONS: The RPGN grading system was more useful to predict six-month overall and ESRD-free survival than the EUVAS-defined severity or FFS 2009. en-copyright= kn-copyright= en-aut-name=SadaKen-ei en-aut-sei=Sada en-aut-mei=Ken-ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HarigaiMasayoshi en-aut-sei=Harigai en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AmanoKoichi en-aut-sei=Amano en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AtsumiTatsuya en-aut-sei=Atsumi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimotoShouichi en-aut-sei=Fujimoto en-aut-mei=Shouichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YuzawaYukio en-aut-sei=Yuzawa en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakasakiYoshinari en-aut-sei=Takasaki en-aut-mei=Yoshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BannoShogo en-aut-sei=Banno en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=KobayashiMasaki en-aut-sei=Kobayashi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UsuiJoichi en-aut-sei=Usui en-aut-mei=Joichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamagataKunihiro en-aut-sei=Yamagata en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HommaSakae en-aut-sei=Homma en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=DobashiHiroaki en-aut-sei=Dobashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TsuboiNaotake en-aut-sei=Tsuboi en-aut-mei=Naotake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IshizuAkihiro en-aut-sei=Ishizu en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OkadaYasunori en-aut-sei=Okada en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ArimuraYoshihiro en-aut-sei=Arimura en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MatsuoSeiichi en-aut-sei=Matsuo en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil= Department of Nephrology, Rheumatology, Endocrinology and Metabolism , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Rheumatology, Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University kn-affil= affil-num=3 en-affil=Department of Rheumatology and Clinical Immunology , Saitama Medical Center, Saitama Medical University kn-affil= affil-num=4 en-affil=Division of Rheumatology, Endocrinology and Nephrology at the Graduate School of Medicine , Hokkaido University kn-affil= affil-num=5 en-affil=Department of Hemovascular Medicine and Artificial Organs, Faculty of Medicine , Miyazaki University kn-affil= affil-num=6 en-affil=Department of Nephrology , Fujita Health University School of Medicine kn-affil= affil-num=7 en-affil=Department of Internal Medicine and Rheumatology , Juntendo University School of Medicine kn-affil= affil-num=8 en-affil=Division of Rheumatology and Nephrology, Department of Internal Medicine , Aichi Medical University School of Medicine kn-affil= affil-num=9 en-affil=Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology kn-affil= affil-num=10 en-affil=Department of Nephrology , Tokyo Medical University Ibaraki Medical Center kn-affil= affil-num=11 en-affil=Department of Nephrology, Faculty of Medicine , University of Tsukuba kn-affil= affil-num=12 en-affil=Department of Nephrology, Faculty of Medicine , University of Tsukuba kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine , Toho University Omori Medical Center kn-affil= affil-num=14 en-affil=Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine , Kagawa University kn-affil= affil-num=15 en-affil=Department of Nephrology, Internal Medicine , Nagoya University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Faculty of Health Sciences , Hokkaido University kn-affil= affil-num=17 en-affil=Department of Chronic Kidney Disease and Peritoneal Dialysis , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Pathology , Keio University School of Medicine kn-affil= affil-num=19 en-affil=Nephrology and Rheumatology, First Department of Internal Medicine , Kyorin University School of Medicine kn-affil= affil-num=20 en-affil=Department of Nephrology, Internal Medicine , Nagoya University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Okayama University Hospital kn-affil= en-keyword=Antineutrophil cytoplasmic antibody-associated vasculitis kn-keyword=Antineutrophil cytoplasmic antibody-associated vasculitis en-keyword=Eosinophilic granulomatosis with polyangiitis kn-keyword=Eosinophilic granulomatosis with polyangiitis en-keyword=Granulomatosis with polyangiitis kn-keyword=Granulomatosis with polyangiitis en-keyword=Inception cohort kn-keyword=Inception cohort en-keyword=Microscopic polyangiitis kn-keyword=Microscopic polyangiitis END start-ver=1.4 cd-journal=joma no-vol=485 cd-vols= no-issue=2 article-no= start-page=261 end-page=266 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=201704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SRSF1-3 contributes to diversification of the immunoglobulin variable region gene by promoting accumulation of AID in the nucleus en-subtitle= kn-subtitle= en-abstract= kn-abstract=　Activation-induced cytidine deaminase (AID) is essential for diversification of the Ig variable region (IgV). AID is excluded from the nucleus, where it normally functions. However, the molecular mechanisms responsible for regulating AID localization remain to be elucidated. The SR-protein splicing factor SRSF1 is a nucleocytoplasmic shuttling protein, a splicing isoform of which called SRSF1-3, has previously been shown to contribute to IgV diversification in chicken DT40 cells. In this study, we examined whether SRSF1-3 functions in IgV diversification by promoting nuclear localization of AID. AID expressed alone was localized predominantly in the cytoplasm. In contrast, co-expression of AID with SRSF1-3 led to the nuclear accumulation of both AID and SRSF1-3 and the formation of a protein complex that contained them both, although SRSF1-3 was dispensable for nuclear import of AID. Expression of either SRSF1-3 or a C-terminally-truncated AID mutant increased IgV diversification in DT40 cells. However, overexpression of exogenous SRSF1-3 was unable to further enhance IgV diversification in DT40 cells expressing the truncated AID mutant, although SRSF1-3 was able to form a protein complex with the AID mutant. These results suggest that SRSF1-3 promotes nuclear localization of AID probably by forming a nuclear protein complex, which might stabilize nuclear AID and induce IgV diversification in an AID C-terminus-dependent manner. en-copyright= kn-copyright= en-aut-name=KawaguchiYuka en-aut-sei=Kawaguchi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NarikiHiroaki en-aut-sei=Nariki en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawamotoNaoko en-aut-sei=Kawamoto en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanehiroYuichi en-aut-sei=Kanehiro en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyazakiSatoshi en-aut-sei=Miyazaki en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiMari en-aut-sei=Suzuki en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=KanayamaNaoki en-aut-sei=Kanayama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=AID kn-keyword=AID en-keyword=DT40 kn-keyword=DT40 en-keyword=Gene conversion kn-keyword=Gene conversion en-keyword=Ig kn-keyword=Ig en-keyword=SRSF1 kn-keyword=SRSF1 en-keyword=Somatic hypermutation kn-keyword=Somatic hypermutation END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=4 article-no= start-page=449 end-page=454 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=201704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Usefulness of serum 5-S-cysteinyl-dopa as a biomarker for predicting prognosis and detecting relapse in patients with advanced stage malignant melanoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= With the recent development of novel molecular targeted drugs for advanced stage malignant melanoma (MM), including RAF and mitogen-activated protein kinase kinase inhibitors and immune checkpoint blockers, the early detection of relapse is important for managing patients with MM. In this study, we retrospectively analyzed two conventional serum biomarkers, 5-S-cysteinyl-dopa and lactate dehydrogenase, in patients with MM (n = 140) who were treated at a single Japanese institute from June 2007 to June 2015. At the initial hospital visit, serum 5-S-cysteinyl-dopa levels were significantly increased in patients with stages III (n = 38) and IV (n = 20) MM compared with patients with stages 0-II (n = 62) MM. In addition, in patients with stages III and IV MM, serum 5-S-cysteinyl-dopa levels of more than 15.0 nmol/L at initial hospital visit correlated with a poor prognosis. In 11 of 14 patients whose disease progressed during follow up (mostly from stages III-IV), serum 5-S-cysteinyl-dopa levels exceeded the normal limit of 10.0 nmol/L during the clinical detection of distant metastases. These results indicate the usefulness of measuring serum 5-S-cysteinyl-dopa levels at initial hospital visit and during follow up for early and effective therapeutic interventions using newly developed molecular targeted drugs. en-copyright= kn-copyright= en-aut-name=HiroshiUmemura en-aut-sei=Hiroshi en-aut-mei=Umemura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KajiTatsuya en-aut-sei=Kaji en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukaMasaki en-aut-sei=Otsuka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsagoeKenji en-aut-sei=Asagoe en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakataMinoru en-aut-sei=Takata en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Dermatology, Shizuoka Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Dermatology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=5-S-cysteinyl-dopa kn-keyword=5-S-cysteinyl-dopa en-keyword=biomarker kn-keyword=biomarker en-keyword=lactate dehydrogenase kn-keyword=lactate dehydrogenase en-keyword=malignant melanoma kn-keyword=malignant melanoma en-keyword=serum 5-S-CD kn-keyword=serum 5-S-CD END start-ver=1.4 cd-journal=joma no-vol=543 cd-vols= no-issue=7643 article-no= start-page=131 end-page=135 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=201703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Light-induced structural changes and the site of O=O bond formation in PSII caught by XFEL en-subtitle= kn-subtitle= en-abstract= kn-abstract= Photosystem II (PSII) is a huge membrane-protein complex consisting of 20 different subunits with a total molecular mass of 350 kDa for a monomer. It catalyses light-driven water oxidation at its catalytic centre, the oxygen-evolving complex (OEC). The structure of PSII has been analysed at 1.9 Å resolution by synchrotron radiation X-rays, which revealed that the OEC is a Mn4CaO5 cluster organized in an asymmetric, 'distorted-chair' form. This structure was further analysed with femtosecond X-ray free electron lasers (XFEL), providing the 'radiation damage-free' structure. The mechanism of O=O bond formation, however, remains obscure owing to the lack of intermediate-state structures. Here we describe the structural changes in PSII induced by two-flash illumination at room temperature at a resolution of 2.35 Å using time-resolved serial femtosecond crystallography with an XFEL provided by the SPring-8 ångström compact free-electron laser. An isomorphous difference Fourier map between the two-flash and dark-adapted states revealed two areas of apparent changes: around the QB/non-haem iron and the Mn4CaO5 cluster. The changes around the QB/non-haem iron region reflected the electron and proton transfers induced by the two-flash illumination. In the region around the OEC, a water molecule located 3.5 Å from the Mn4CaO5 cluster disappeared from the map upon two-flash illumination. This reduced the distance between another water molecule and the oxygen atom O4, suggesting that proton transfer also occurred. Importantly, the two-flash-minus-dark isomorphous difference Fourier map showed an apparent positive peak around O5, a unique μ4-oxo-bridge located in the quasi-centre of Mn1 and Mn4 (refs 4,5). This suggests the insertion of a new oxygen atom (O6) close to O5, providing an O=O distance of 1.5 Å between these two oxygen atoms. This provides a mechanism for the O=O bond formation consistent with that proposed previously en-copyright= kn-copyright= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkitaFusamichi en-aut-sei=Akita en-aut-mei=Fusamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugaharaMichihiro en-aut-sei=Sugahara en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuboMinoru en-aut-sei=Kubo en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakaneTakanori en-aut-sei=Nakane en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamashitaKeitaro en-aut-sei=Yamashita en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UmenaYasufumi en-aut-sei=Umena en-aut-mei=Yasufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakabayashiMakoto en-aut-sei=Nakabayashi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamaneTakahiro en-aut-sei=Yamane en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakanoTakamitsu en-aut-sei=Nakano en-aut-mei=Takamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SuzukiMamoru en-aut-sei=Suzuki en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MasudaTetsuya en-aut-sei=Masuda en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=InoueShigeyuki en-aut-sei=Inoue en-aut-mei=Shigeyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KimuraTetsunari en-aut-sei=Kimura en-aut-mei=Tetsunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NomuraTakashi en-aut-sei=Nomura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YonekuraShinichiro en-aut-sei=Yonekura en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YuLong-Jiang en-aut-sei=Yu en-aut-mei=Long-Jiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SakamotoTomohiro en-aut-sei=Sakamoto en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MotomuraTaiki en-aut-sei=Motomura en-aut-mei=Taiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 ORCID= en-aut-name=KatoYuki en-aut-sei=Kato en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=NoguchiTakumi en-aut-sei=Noguchi en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TonoKensuke en-aut-sei=Tono en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=JotiYasumasa en-aut-sei=Joti en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KameshimaTakashi en-aut-sei=Kameshima en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=HatsuiTakaki en-aut-sei=Hatsui en-aut-mei=Takaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NangoEriko en-aut-sei=Nango en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=TanakaRie en-aut-sei=Tanaka en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=NaitowHisashi en-aut-sei=Naitow en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=MatsuuraYoshinori en-aut-sei=Matsuura en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=YamashitaAyumi en-aut-sei=Yamashita en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=YamamotoMasaki en-aut-sei=Yamamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=NurekiOsamu en-aut-sei=Nureki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=YabashiMakina en-aut-sei=Yabashi en-aut-mei=Makina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=IshikawaTetsuya en-aut-sei=Ishikawa en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 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=37 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=38 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=4 en-affil=Japan Science and Technology Agency, PRESTO kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=7 en-affil=RIKEN SPring-8 Center 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=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=12 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=13 en-affil=Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=14 en-affil=Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=15 en-affil=Department of Chemistry, Graduate School of Science, Kobe University kn-affil= affil-num=16 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=17 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=18 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=19 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=20 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=21 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=22 en-affil=Division of Material Science, Graduate School of Science, Nagoya University kn-affil= affil-num=23 en-affil=Division of Material Science, Graduate School of Science, Nagoya University kn-affil= affil-num=24 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=25 en-affil=Japan Synchrotron Radiation Research Institute kn-affil= affil-num=26 en-affil=Japan Synchrotron Radiation Research Institute46 kn-affil= affil-num=27 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=28 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=29 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=30 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=31 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=32 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=33 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=34 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=35 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=36 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=37 en-affil=RIKEN SPring-8 Center kn-affil= affil-num=38 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=6 article-no= start-page=449 end-page=453 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurological Recovery after Posterior Spinal Surgery in Patients with Metastatic Epidural Spinal Cord Compression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metastatic epidural spinal cord compression (MESCC) is a common complication in patients with a malignant tumor, but it is difficult to decide the proper time to perform the necessary surgery. Here we analyzed the prognostic factors for postoperative walking ability. We retrospectively reviewed the cases of 112 MESCC patients treated surgically at our institute and divided them into ambulatory (n＝ 88) and non-ambulatory (n＝24) groups based on their American Spinal Injury Association (ASIA) Impairment Scale grades at the final follow-up. We also classified the patients preoperatively using the revised Tokuhashi score. We assessed the correlation between preoperative or intraoperative factors and postoperative walking ability in both groups. Of the 10 patients classified preoperatively as grade A or B, 2 (20 ) were ambulatory at the final follow-up. Of the 102 patients classified preoperatively as grade C, D or E, 86 (84 ) were ambulatory at the final follow-up (p＜0.001). There were no significant differences between the groups in the average total Tokuhashi score. Our analysis revealed that the severity of paralysis significantly affects neurological recovery in patients with MESCC. Patients with MESCC should receive surgery before the preoperative ASIA Impairment Scale grade falls below grade C. en-copyright= kn-copyright= en-aut-name=WatanabeNoriyuki en-aut-sei=Watanabe en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugimotoYoshihisa en-aut-sei=Sugimoto en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=MazakiTetsuro en-aut-sei=Mazaki en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TakigawaTomoyuki en-aut-sei=Takigawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KataokaMasaki en-aut-sei=Kataoka en-aut-mei=Masaki 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 Medical Materials for Musculoskeletal Reconstruction, 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=metastatic epidural spinal cord compression kn-keyword=metastatic epidural spinal cord compression en-keyword=American Spinal Injury Association Impairment Scale kn-keyword=American Spinal Injury Association Impairment Scale en-keyword=Tokuhashi score kn-keyword=Tokuhashi score en-keyword=walking ability kn-keyword=walking ability en-keyword=prognostic factor kn-keyword=prognostic factor END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue=3 article-no= start-page=213 end-page=216 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20161201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Probable IgG4-related thyroiditis with cervical lymphadenopathy kn-title=リンパ節転移を伴う甲状腺癌を疑ったIgG4関連甲状腺炎（準確診群）の1 切除例 en-subtitle= kn-subtitle= en-abstract= kn-abstract=　We present a case of probably IgG4-related thyroiditis with lymphadenopathy. The patient was a 70-year-old Japanese female who was undergoing hemodialysis and had undergone a right hemi-thyroidectomy in 1989 due to carcinoma. In December 2010, an ultrasonography study revealed a hypoechoic small lesion in thyroid gland. When the patient was admitted to our hospital in November 2013, the lesion and regional lymph nodes had enlarged and we suspected that they were metastatic thyroid cancer. We performed a residual total thyroidectomy and regional lymph node dissection in August 2014. At that time, lymphoplasmacytic infiltration and fibrosis were observed histopathologically in thyroid tissue. Immunohistochemical studies revealed infiltrated lymphocytes and plasma cells were markedly IgG-positive, and the ratio of IgG4-positive to IgG-positive cells was over 40%. We therefore diagnosed the patient with IgG4-related thyroiditis. The cervical lymph nodes were metastases of papillary carcinoma from 25 years earlier. The patient remains well without any recurrences 33 months after the surgery. en-copyright= kn-copyright= en-aut-name=KobashiKenta en-aut-sei=Kobashi en-aut-mei=Kenta kn-aut-name=小橋研太 kn-aut-sei=小橋 kn-aut-mei=研太 aut-affil-num=1 ORCID= en-aut-name=IshiiHiroshi en-aut-sei=Ishii en-aut-mei=Hiroshi kn-aut-name=石井博 kn-aut-sei=石井 kn-aut-mei=博 aut-affil-num=2 ORCID= en-aut-name=NishiyamaKanako en-aut-sei=Nishiyama en-aut-mei=Kanako kn-aut-name=西山加那子 kn-aut-sei=西山 kn-aut-mei=加那子 aut-affil-num=3 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name=松三雄騎 kn-aut-sei=松三 kn-aut-mei=雄騎 aut-affil-num=4 ORCID= en-aut-name=HatanoMasahide en-aut-sei=Hatano en-aut-mei=Masahide kn-aut-name=羽田野雅英 kn-aut-sei=羽田野 kn-aut-mei=雅英 aut-affil-num=5 ORCID= en-aut-name=FujiwaraMasamitsu en-aut-sei=Fujiwara en-aut-mei=Masamitsu kn-aut-name=藤原雅光 kn-aut-sei=藤原 kn-aut-mei=雅光 aut-affil-num=6 ORCID= en-aut-name=KurokawaTatsuo en-aut-sei=Kurokawa en-aut-mei=Tatsuo kn-aut-name=黒河達雄 kn-aut-sei=黒河 kn-aut-mei=達雄 aut-affil-num=7 ORCID= en-aut-name=TsunemitsuKensuke en-aut-sei=Tsunemitsu en-aut-mei=Kensuke kn-aut-name=常光謙輔 kn-aut-sei=常光 kn-aut-mei=謙輔 aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Surgery, Saiseikai Saijo Hospital kn-affil=済生会西条病院　外科 affil-num=2 en-affil=Department of Surgery, Saiseikai Saijo Hospital kn-affil=済生会西条病院　外科 affil-num=3 en-affil=Breast Center, Ehime University Hospital kn-affil=愛媛大学医学部附属病院　乳腺センター affil-num=4 en-affil=Department of Surgery, Saiseikai Saijo Hospital kn-affil=済生会西条病院　外科 affil-num=5 en-affil=Department of Surgery, Saiseikai Saijo Hospital kn-affil=済生会西条病院　外科 affil-num=6 en-affil=Department of Surgery, Imabariishikaishimin Hospital kn-affil=今治医師会市民病院　外科 affil-num=7 en-affil=Department of Surgery, Saiseikai Saijo Hospital kn-affil=済生会西条病院　外科 affil-num=8 en-affil=Department of Surgery, Saiseikai Saijo Hospital kn-affil=済生会西条病院　外科 en-keyword=IgG4 関連甲状腺炎（IgG4-related thyroiditis） kn-keyword=IgG4 関連甲状腺炎（IgG4-related thyroiditis） en-keyword=橋本病（Hashimoto’s thyroiditis） kn-keyword=橋本病（Hashimoto’s thyroiditis） en-keyword=転移性リンパ節腫瘍（metastatic lymph node tumor） kn-keyword=転移性リンパ節腫瘍（metastatic lymph node tumor） en-keyword=慢性腎不全（chronic renal failure） kn-keyword=慢性腎不全（chronic renal failure） END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=4 article-no= start-page=307 end-page=311 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Open-Label Feasibility Trial of Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Major Depressive Episodes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Repetitive transcranial magnetic stimulation (rTMS) has been reported to be a new treatment option for treatment-resistant depression. In Japan, there has been limited research into its feasibility, efficacy, and tolerability. We have launched a trial of rTMS for treating medication-resistant major depressive disorder and bipolar depression. We are investigating low-frequency rTMS to the right dorsolateral prefrontal cortex and traditional high-frequency rTMS to the left dorsolateral prefrontal cortex, in 20 patients. The primary outcome of the study is the treatment completion rate. This study will provide new data on the usefulness of rTMS for treatment-resistant depression in Japan. en-copyright= kn-copyright= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InagakiMasatoshi en-aut-sei=Inagaki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiguchiYuji en-aut-sei=Higuchi en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchitomiYosuke en-aut-sei=Uchitomi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KodamaMasafumi en-aut-sei=Kodama en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KishiYoshiki en-aut-sei=Kishi en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamadaNorihito en-aut-sei=Yamada en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Innovation Center for Supportive, Palliative and Psychosocial Care, National Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=7 en-affil=Okayama Psychiatric Medical Center kn-affil= affil-num=8 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= en-keyword=repetitive transcranial magnetic stimulation kn-keyword=repetitive transcranial magnetic stimulation en-keyword=depression kn-keyword=depression en-keyword=treatment resistance kn-keyword=treatment resistance en-keyword=low frequency kn-keyword=low frequency END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=4 article-no= start-page=261 end-page=268 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Diagnostic Algorithm for Eosinophilic Granulomatosis with Polyangiitis Initially Diagnosed as Lumbar Disc Hernia or Lumbar Spinal Stenosis: Personal Experience and Review of the Literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is a rare systemic vasculitis and is difficult to diagnose. EGPA has a number of symptoms including peripheral dysesthesia caused by mononeuropathy multiplex, which is similar to radiculopathy due to lumbar disc hernia or lumbar spinal stenosis. Therefore, EGPA patients with mononeuropathy multiplex often visit orthopedic clinics, but orthopedic doctors and spine neurosurgeons have limited experience in diagnosing EGPA because of its rarity. We report a consecutive series of patients who were initially diagnosed as having lumbar disc hernia or lumbar spinal stenosis by at least 2 medical institutions from March 2006 to April 2013 but whose final diagnosis was EGPA. All patients had past histories of asthma or eosinophilic pneumonia, and four out of five had peripheral edema. Laboratory data showed abnormally increased eosinophil counts, and nerve conduction studies of all patients revealed axonal damage patterns. All patients recovered from paralysis to a functional level after high-dose steroid treatment. We shortened the duration of diagnosis from 49 days to one day by adopting a diagnostic algorithm after experiencing the first case. en-copyright= kn-copyright= en-aut-name=NagataKosei en-aut-sei=Nagata en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoShinichi en-aut-sei=Yamamoto en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyoshiKota en-aut-sei=Miyoshi en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoMasaki en-aut-sei=Sato en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ArinoYusuke en-aut-sei=Arino en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MikamiYoji en-aut-sei=Mikami en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Yokohama Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Yokohama Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Yokohama Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Yokohama Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Yokohama Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Yokohama Rosai Hospital kn-affil= en-keyword=eosinophilic granulomatosis with polyangiitis kn-keyword=eosinophilic granulomatosis with polyangiitis en-keyword=mononeuropathy multiplex kn-keyword=mononeuropathy multiplex en-keyword=lumbar disc hernia kn-keyword=lumbar disc hernia en-keyword=lumbar spinal stenosis kn-keyword=lumbar spinal stenosis en-keyword=nerve conduction study kn-keyword=nerve conduction study 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=2016 dt-pub=20160325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=BCGにおけるc-di-GMPの菌体内過剰合成の増殖への影響に関する研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SenoMasaki en-aut-sei=Seno en-aut-mei=Masaki kn-aut-name=妹尾昌紀 kn-aut-sei=妹尾 kn-aut-mei=昌紀 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 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=2016 dt-pub=20160325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=好中球エラスターゼ阻害薬は体外肺灌流システム中の肺機能を改善する kn-title=A neutrophil elastase inhibitor improves lung function during ex vivo lung perfusion en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HaradaMasaki en-aut-sei=Harada en-aut-mei=Masaki kn-aut-name=原田昌明 kn-aut-sei=原田 kn-aut-mei=昌明 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=3 article-no= start-page=1 end-page=27 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160319 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A Study of Assistance on Supporters of Regional Revitalization and Their Retention: “Local Community Revitalizing Troops” Project and Community Sustainability kn-title=地域サポート人材の定着とその支援のあり方について ―地域おこし協力隊制度と地域社会のサステイナビリティ― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NakaoHiroyuki en-aut-sei=Nakao en-aut-mei=Hiroyuki kn-aut-name=中尾裕幸 kn-aut-sei=中尾 kn-aut-mei=裕幸 aut-affil-num=1 ORCID= en-aut-name=HiranoMasaki en-aut-sei=Hirano en-aut-mei=Masaki kn-aut-name=平野正樹 kn-aut-sei=平野 kn-aut-mei=正樹 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=美作市 affil-num=2 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=2 article-no= start-page=53 end-page=80 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Trends in Okayama Prefectural Finance after the Japanese asset price bubble: A review of financial conditions during the Nagano and Ishii administrations kn-title=バブル期以降の岡山県財政の変容 −長野・石井県政時代の財政状況を振り返ってみて− en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KameyamaTeiji en-aut-sei=Kameyama en-aut-mei=Teiji kn-aut-name=亀山定司 kn-aut-sei=亀山 kn-aut-mei=定司 aut-affil-num=1 ORCID= en-aut-name=HiranoMasaki en-aut-sei=Hirano en-aut-mei=Masaki kn-aut-name=平野正樹 kn-aut-sei=平野 kn-aut-mei=正樹 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=岡山県 affil-num=2 en-affil= kn-affil=岡山大学 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=2015 dt-pub=20151231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=日本の1施設における皮膚原発悪性黒色腫102患者に対するセンチネルリンパ節生検 kn-title=Sentinel lymph node biopsy for 102 patients with primary cutaneous melanoma at a single Japanese institute en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OtsukaMasaki en-aut-sei=Otsuka en-aut-mei=Masaki kn-aut-name=大塚正樹 kn-aut-sei=大塚 kn-aut-mei=正樹 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=223 end-page=226 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=201512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Spoken Dialog System with Redundant Response to Prevent User Misunderstanding en-subtitle= kn-subtitle= en-abstract= kn-abstract=We propose a spoken dialog strategy for car navigation systems to facilitate safe driving. To drive safely, drivers need to concentrate on their driving; however, their concentration may be disrupted due to disagreement with their spoken dialog system. Therefore, we need to solve the problems of user misunderstandings as well as misunderstanding of spoken dialog systems. For this purpose, we introduced a driver workload level in spoken dialog management in order to prevent user misunderstandings. A key strategy of the dialog management is to make speech redundant if the driver’s workload is too high in assuming that the user probably misunderstand the system utterance under such a condition. An experiment was conducted to compare performances of the proposed method and a conventional method using a user simulator. The simulator is developed under the assumption of two types of drivers: an experienced driver model and a novice driver model. Experimental results showed that the proposed strategies achieved better performance than the conventional one for task completion time, task completion rate, and user’s positive speech rate. In particular, these performance differences are greater for novice users than for experienced users. en-copyright= kn-copyright= en-aut-name=YamaokaMasaki en-aut-sei=Yamaoka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraSunao en-aut-sei=Hara en-aut-mei=Sunao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AbeMasanobu en-aut-sei=Abe en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=岡山大学大学院自然科学研究科 affil-num=3 en-affil= kn-affil=岡山大学大学院自然科学研究科 END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=3 article-no= start-page=e58791 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1−/− mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1−/− mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1−/− mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1−/− mice. Transplantation of MCP-1−/− bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1−/− mice increased lung metastasis. The primary tumors of MCP-1−/− mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1−/− mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment. en-copyright= kn-copyright= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HowardO. M. Zack en-aut-sei=Howard en-aut-mei=O. M. Zack kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoToshihiro en-aut-sei=Ito en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuwabaraMasaki en-aut-sei=Kuwabara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=ChenKeqiang en-aut-sei=Chen en-aut-mei=Keqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiuYing en-aut-sei=Liu en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LiuMingyong en-aut-sei=Liu en-aut-mei=Mingyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OppenheimJoost J. en-aut-sei=Oppenheim en-aut-mei=Joost J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WangJi Ming en-aut-sei=Wang en-aut-mei=Ji Ming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=2 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=3 en-affil= kn-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=4 en-affil= kn-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=5 en-affil= kn-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=6 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=7 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=8 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=9 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute affil-num=10 en-affil= kn-affil=Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute END start-ver=1.4 cd-journal=joma no-vol=517 cd-vols= no-issue= article-no= start-page=99 end-page=103 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20150101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Native structure of photosystem II at 1.95 Å resolution viewed by femtosecond X-ray pulses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosynthesis converts light energy into biologically useful chemical energy vital to life on Earth. The initial reaction of photosynthesis takes place in photosystem II (PSII), a 700-kilodalton homodimeric membrane protein complex which catalyses photo-oxidation of water into dioxygen through an S-state cycle of the oxygen evolving complex (OEC). The structure of PSII has been solved by X-ray diffraction (XRD) at 1.9-ångström (Å) resolution, which revealed that the OEC is a Mn4CaO5-cluster coordinated by a well-defined protein environment1. However, extended X-ray absorption fine structure (EXAFS) studies showed that the manganese cations in the OEC are easily reduced by X-ray irradiation2, and slight differences were found in the Mn–Mn distances between the results of XRD1, EXAFS3–7 and theoretical studies8–14. Here we report a ‘radiation-damage-free’ structure of PSII from Thermosynechococcus vulcanus in the S1 state at a resolution of 1.95 Å using femtosecond X-ray pulses of the SPring-8 ångström compact free-electron laser (SACLA) and a huge number of large, highly isomorphous PSII crystals. Compared with the structure from XRD, the OEC in the X-ray free electron laser structure has Mn–Mn distances that are shorter by 0.1–0.2 Å. The valences of each manganese atom were tentatively assigned as Mn1D(III), Mn2C(IV), Mn3B(IV) and Mn4A(III), based on the average Mn–ligand distances and analysis of the Jahn–Teller axis on Mn(III). One of the oxo-bridged oxygens, O5, has significantly longer Mn–O distances in contrast to the other oxo-oxygen atoms, suggesting that it is a hydroxide ion instead of a normal oxygen dianion and therefore may serve as one of the substrate oxygen atoms. These findings provide a structural basis for the mechanism of oxygen evolution, and we expect that this structure will provide a blueprint for design of artificial catalysts for water oxidation. en-copyright= kn-copyright= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkitaFusamichi en-aut-sei=Akita en-aut-mei=Fusamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirataKunio en-aut-sei=Hirata en-aut-mei=Kunio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UenoGo en-aut-sei=Ueno en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiHironori en-aut-sei=Murakami en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimizuTetsuya en-aut-sei=Shimizu en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamashitaKeitaro en-aut-sei=Yamashita en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoMasaki en-aut-sei=Yamamoto en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AgoHideo en-aut-sei=Ago en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil= kn-affil=Photosynthesis Research Center, Graduate School of Natural Science and Technology, Okayama University affil-num=2 en-affil= kn-affil=Photosynthesis Research Center, Graduate School of Natural Science and Technology, Okayama University affil-num=3 en-affil= kn-affil=RIKEN SPring-8 Center affil-num=4 en-affil= kn-affil=RIKEN SPring-8 Center affil-num=5 en-affil= kn-affil=RIKEN SPring-8 Center affil-num=6 en-affil= kn-affil=Photosynthesis Research Center, Graduate School of Natural Science and Technology, Okayama University affil-num=7 en-affil= kn-affil=Photosynthesis Research Center, Graduate School of Natural Science and Technology, Okayama University affil-num=8 en-affil= kn-affil=RIKEN SPring-8 Center affil-num=9 en-affil= kn-affil=RIKEN SPring-8 Center affil-num=10 en-affil= kn-affil=RIKEN SPring-8 Center affil-num=11 en-affil= kn-affil=Photosynthesis Research Center, Graduate School of Natural Science and Technology, Okayama University END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=6 article-no= start-page=670 end-page=675 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=201411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Increase of DC-LAMP+ mature dendritic cell subsets in dermatopathic lymphadenitis of mycosis fungoides en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Little is known about the immunological milieu of the skin-draining lymph nodes (LNs) in mycosis fungoides (MF). Objectives: We studied dendritic cell (DC) subsets in the dermatopathic lymphadenitis of MF patients. Methods: We immunohistochemically examined DC subsets and their distribution in 16 LN samples from 14 patients with MF (N1 LN, eight patients; N2, four; and N3, four), and we compared them with non-metastatic sentinel LNs from eight patients with melanoma. Results: The number of S-100 protein+ DCs was markedly increased in the LNs from the MF patients and the major component was DC-LAMP+ mature DCs in the outer and paracortex areas, where DC-SIGN+ immature DCs were relatively decreased in proportion. In contrast, DC-SIGN+ cells were relatively increased in proportion compared to DC-LAMP+ cells in the medulla. Although no significant difference was observed in the proportions of CD1a+ or Langerin+ DCs among the N1, N2, and N3 nodes, CD163+ M2-type macrophages were increased in number in the N2 and N3 nodes. Conclusions: Our observations indicate that mature DCs accumulate in the outer and paracortex areas in dermatopathic lymphadenitis and M2-type macrophages might increase in number during disease progression. en-copyright= kn-copyright= en-aut-name=TadaKotaro en-aut-sei=Tada en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamadaToshihisa en-aut-sei=Hamada en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsagoeKenji en-aut-sei=Asagoe en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UmemuraHiroshi en-aut-sei=Umemura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Mizuno-IkedaKazuko en-aut-sei=Mizuno-Ikeda en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AoyamaYumi en-aut-sei=Aoyama en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsukaMasaki en-aut-sei=Otsuka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Dermatology, Okayama Medical Center affil-num=4 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=7 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences en-keyword=Mycosis fungoides kn-keyword=Mycosis fungoides en-keyword=dendritic cell kn-keyword=dendritic cell en-keyword=dermatopathic lymphadenitis kn-keyword=dermatopathic lymphadenitis en-keyword=DC-LAMP kn-keyword=DC-LAMP en-keyword=DC-SIGN kn-keyword=DC-SIGN en-keyword=M2-type macrophage kn-keyword=M2-type macrophage END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=1 article-no= start-page=17 end-page=27 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=201502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Assessment of Melanoma-Initiating Cell Markers and Conventional Parameters in Sentinel Lymph Nodes of Malignant Melanoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sentinel lymph node (SLN) biopsies have widely been used for the detection of occult LN metastasis of malignant melanoma (MM). In addition to conventional biomarkers, we assessed the diagnostic and prognostic significance of melanoma-initiating cell (MIC) markers in SLNs of MM. We examined the expressions of gp100, MART-1 and tyrosinase mRNA for routine diagnosis and those of ABCB5, CD133, nestin, KDM5B, NGFR and RANK mRNA as MIC markers. The presence of micrometastasis was confirmed immunohistochemically using antibodies to S-100, HMB-45, MART-1, and tyrosinase. Discordance between immunohistochemical and molecular data was observed in 14 of 70 (20.0%) patients, among whom five (7.1%) were positive for only molecular markers;two of these five patients tested positive for micrometastasis by repeated immunohistochemical stainings. The quantitative expression levels of gp100, MART-1, and tyrosinase mRNA were significantly higher in the metastatic LNs;the cut-off values remain to be elucidated. ABCB5 mRNA expression was detected more frequently in the metastatic SLNs (p＜0.05) and in the group of patients with recurrence. To make a definite diagnosis of metastasis, we still need a combination of immunohistochemical and molecular probes. ABCB5 might be a suitable molecular marker for the detection of melanoma-initiating cells in SLNs. en-copyright= kn-copyright= en-aut-name=SuzukiNorihiro en-aut-sei=Suzuki en-aut-mei=Norihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakataMinoru en-aut-sei=Takata en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShirafujiYoshinori en-aut-sei=Shirafuji en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukaMasaki en-aut-sei=Otsuka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsagoeKenji en-aut-sei=Asagoe en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HattaNaohito en-aut-sei=Hatta en-aut-mei=Naohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Department of Dermatology, Okayama Medical Center affil-num=7 en-affil= kn-affil=Department of Dermatology, Toyama Prefectural Central Hospital affil-num=8 en-affil= kn-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=melanoma kn-keyword=melanoma en-keyword=cancer-initiating cell kn-keyword=cancer-initiating cell en-keyword=sentinel lymph node kn-keyword=sentinel lymph node en-keyword=ABCB5 kn-keyword=ABCB5 END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue= article-no= start-page=25 end-page=33 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20131218 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-term effect of cinacalcet hydrochloride on abdominal aortic calcification in patients on hemodialysis with secondary hyperparathyroidism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Secondary hyperparathyroidism (SHPT) is one of the common complications in dialysis patients, and is associated with increased risk of vascular calcification. The effects of cinacalcet hydrochloride treatment on bone and mineral metabolism have been previously reported, but the benefit of cinacalcet on vascular calcification remains uncertain. The aim of this study was to evaluate the impact of cinacalcet on abdominal aortic calcification in dialysis patients. Subjects and methods: Patients were on maintenance hemodialysis with insufficiently controlled SHPT (intact parathyroid hormone [PTH] >180 pg/mL) by conventional therapies. All subjects were initially administered 25 mg cinacalcet daily, with concomitant use of calcitriol analogs. Abdominal aortic calcification was annually evaluated by calculating aortic calcification area index (ACAI) using multidetector computed tomography (MDCT), from 12 months before to 36 months after the initiation of cinacalcet therapy. Results: Twenty-three patients were analyzed in this study. The mean age was 59.0±8.7 years, 34.8% were women, and the mean dialysis duration was 163.0±76.0 months. After administration of cinacalcet, serum levels of intact PTH, phosphorus, and calcium significantly decreased, and mean Ca × P values significantly decreased from 67.4±7.9 mg2/dL2 to 52±7.7 mg2/dL2. Although the ACAI value did not decrease during the observation period, the increase in ACAI between 24 months and 36 months after cinacalcet administration was significantly suppressed. Conclusion: Long-term administration of cinacalcet was associated with reduced progression of abdominal aortic calcification, and achieving appropriate calcium and phosphorus levels may reduce the rates of cardiovascular events and mortality in patients on hemodialysis. en-copyright= kn-copyright= en-aut-name=NakayamaKazunori en-aut-sei=Nakayama en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaoKazushi en-aut-sei=Nakao en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakatoriYuji en-aut-sei=Takatori en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueJunko en-aut-sei=Inoue en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KojoShoichirou en-aut-sei=Kojo en-aut-mei=Shoichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkagiShigeru en-aut-sei=Akagi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukushimaMasaki en-aut-sei=Fukushima en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=7 en-affil= kn-affil=Shigei Medical Research Hospital affil-num=8 en-affil= kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=abdominal aortic calcification kn-keyword=abdominal aortic calcification en-keyword=cinacalcet hydrochloride kn-keyword=cinacalcet hydrochloride en-keyword=hemodialysis kn-keyword=hemodialysis END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=2 article-no= start-page=59 end-page=85 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A Study on the Expiration of the Calculation upon Mergers of Local Tax Allocation - Do Intergovernmental Fiscal Relations Keep Working? - kn-title=地方交付税の合併算定替え終了が市町村に及ぼす影響 ―財源調整機能は維持されるか― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OtaYuji en-aut-sei=Ota en-aut-mei=Yuji kn-aut-name=太田裕二 kn-aut-sei=太田 kn-aut-mei=裕二 aut-affil-num=1 ORCID= en-aut-name=HiraoMasaki en-aut-sei=Hirao en-aut-mei=Masaki kn-aut-name=平野正樹 kn-aut-sei=平野 kn-aut-mei=正樹 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= 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=2013 dt-pub=20130325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=皮膚創傷治癒過程におけるCCN4/WISP-1遺伝子の役割 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MasakiAsuka en-aut-sei=Masaki en-aut-mei=Asuka kn-aut-name=正木明日香 kn-aut-sei=正木 kn-aut-mei=明日香 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=6 article-no= start-page=443 end-page=447 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluating the Need for and Effect of Percutaneous Transluminal Angioplasty on Arteriovenous Fistulas by Using Total Recirculation Rate per Dialysis Session (“Clearance Gap”) en-subtitle= kn-subtitle= en-abstract= kn-abstract=The functioning of an arteriovenous fistula (AVF) used for vascular access during hemodialysis has been assessed mainly by dilution methods. Although these techniques indicate the immediate recirculation rate, the results obtained may not correlate with Kt/V. In contrast, the clearance gap (CL-Gap) method provides the total recirculation rate per dialysis session and correlates well with Kt/V. We assessed the correlation between Kt/V and CL-Gap as well as the change in radial artery (RA) blood flow speed in the fistula before percutaneous transluminal angioplasty (PTA) in 45 patients undergoing continuous hemodialysis. The dialysis dose during the determination of CL-Gap was 1.2 to 1.4 Kt/V. Patients with a 10% elevation or more than a 10% relative increase in CL-Gap underwent PTA (n＝45), and the values obtained for Kt/V and CL-Gap before PTA were compared with those obtained immediately afterward. The mean RA blood flow speed improved significantly (from 52.9 to 97.5cm/sec) after PTA, as did Kt/V (1.07 to 1.30) and CL-Gap (14.1% to －0.2%). A significant correlation between these differences was apparent (r＝－0.436 and p＝0.003). These findings suggest that calculating CL-Gap may be useful for determining when PTA is required and for assessing the effectiveness of PTA, toward obtaining better dialysis. en-copyright= kn-copyright= en-aut-name=UgawaToyomu en-aut-sei=Ugawa en-aut-mei=Toyomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakuramaKazufumi en-aut-sei=Sakurama en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakaokaMunenori en-aut-sei=Takaoka en-aut-mei=Munenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiwaraYasuhiro en-aut-sei=Fujiwara en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KabashimaNarutoshi en-aut-sei=Kabashima en-aut-mei=Narutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AzumaDaisuke en-aut-sei=Azuma en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorisadaSunao en-aut-sei=Morisada en-aut-mei=Sunao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IidaAtsuyoshi en-aut-sei=Iida en-aut-mei=Atsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TadaKeitaro en-aut-sei=Tada en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShibaNaoki en-aut-sei=Shiba en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SatoNobuo en-aut-sei=Sato en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IchibaShingo en-aut-sei=Ichiba en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KinoKoichi en-aut-sei=Kino en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukushimaMasaki en-aut-sei=Fukushima en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UjikeYoshihito en-aut-sei=Ujike en-aut-mei=Yoshihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil= kn-affil=Department of Emergency Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Surgery, Shigei Medical Research Hospital affil-num=3 en-affil= kn-affil=Department of Epidemiology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Kidney Center, University of Occupational and Environmental Health affil-num=7 en-affil= kn-affil=Department of Internal Medicine, Division of Nephrology, Kagawa Rosai Hospital affil-num=8 en-affil= kn-affil=Department of Emergency Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Department of Emergency Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=10 en-affil= kn-affil=Department of Emergency Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=11 en-affil= kn-affil=Department of Emergency Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=12 en-affil= kn-affil=Department of Emergency Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=13 en-affil= kn-affil=Department of Emergency Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=14 en-affil= kn-affil=Department of Emergency Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=15 en-affil= kn-affil=Department of Emergency Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=16 en-affil= kn-affil=Department of Cardiology, Mahoshi Hospital affil-num=17 en-affil= kn-affil=Department of Internal medicine, Shigei Medical Research Hospital affil-num=18 en-affil= kn-affil=Department of Emergency Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=hemodialysis kn-keyword=hemodialysis en-keyword=recirculation kn-keyword=recirculation en-keyword=clearance gap kn-keyword=clearance gap en-keyword=vascular access kn-keyword=vascular access en-keyword=percutaneous transluminal angioplasty kn-keyword=percutaneous transluminal angioplasty END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=5 article-no= start-page=423 end-page=427 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Duodenal Carcinoma from a Duodenal Diverticulum Mimicking Pancreatic Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=An 81-year-old man was found to have a pancreatic head tumor on abdominal computed tomography (CT) performed during a follow-up visit for sigmoid colon cancer. The tumor had a diameter of 35mm on the CT scan and was diagnosed as pancreatic head carcinoma T3N0M0. The patient was treated with pylorus-preserving pancreaticoduodenectomy. Histopathological examination showed that the tumor had grown within a hollow structure, was contiguous with a duodenal diverticulum, and had partially invaded the pancreas. Immunohistochemistry results were as follows:CK7 negative, CK20 positive, CD10 negative, CDX2 positive, MUC1 negative, MUC2 positive, MUC5AC negative, and MUC6 negative. The tumor was diagnosed as duodenal carcinoma from the duodenal diverticulum. Preoperative imaging showed that the tumor was located in the head of the pancreas and was compressing the common bile duct, thus making it appear like pancreatic cancer. To the best of our knowledge, this is the second report of a case of duodenal carcinoma from a duodenal diverticulum mimicking pancreatic carcinoma. en-copyright= kn-copyright= en-aut-name=FurukawaMasashi en-aut-sei=Furukawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IzumiSadanobu en-aut-sei=Izumi en-aut-mei=Sadanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukudaKazunori en-aut-sei=Tsukuda en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TokumoMasaki en-aut-sei=Tokumo en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakuraiJun en-aut-sei=Sakurai en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ManoShohey en-aut-sei=Mano en-aut-mei=Shohey kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Hospital affil-num=2 en-affil= kn-affil=Department of Surgery, Kagawa Prefectural Central Hospital affil-num=3 en-affil= kn-affil=Department of Thoracic Surgery, Okayama University Hospital affil-num=4 en-affil= kn-affil=Department of Surgery, National Hospital Organization Minami-Okayama Medical Center affil-num=5 en-affil= kn-affil=Department of Diagnostic Radiology, Kagawa Prefectural Central Hospital affil-num=6 en-affil= kn-affil=Department of Pathology, Kagawa Prefectural Central Hospital en-keyword=duodenal carcinoma kn-keyword=duodenal carcinoma en-keyword=duodenal diverticulum kn-keyword=duodenal diverticulum en-keyword=pancreatic carcinoma kn-keyword=pancreatic carcinoma END start-ver=1.4 cd-journal=joma no-vol=72 cd-vols= no-issue=5 article-no= start-page=580 end-page=581 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20110501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ultrahigh-resolution laser photoemission study of URu2Si2 across the hidden-order transition en-subtitle= kn-subtitle= en-abstract= kn-abstract=We have studied the electronic structures of URu2Si2 employing ultrahigh-resolutionlaser angle-resolved photoemission spectroscopy. The change of photoemission spectra is investigated across the hidden-ordertransition, and the emergence of a narrow band is clearly observed near the Fermi level for both (π,0) and (π,π) directions. In addition, it is shown that tuning of light's polarization allows the signal of a hole-like dispersive feature to enhance. These observations prove that laser angle-resolved photoemission spectroscopy is an effective tool for studying the evolution of electronic structures across the hidden-ordertransition in URu2Si2. en-copyright= kn-copyright= en-aut-name=YoshidaRikiya en-aut-sei=Yoshida en-aut-mei=Rikiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraYoshiaki en-aut-sei=Nakamura en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuiMasaki en-aut-sei=Fukui en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HagaYoshinori en-aut-sei=Haga en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoEtsuji en-aut-sei=Yamamoto en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ŌnukiYoshichika en-aut-sei=Ōnuki en-aut-mei=Yoshichika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkawaMario en-aut-sei=Okawa en-aut-mei=Mario kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShinShik en-aut-sei=Shin en-aut-mei=Shik kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraiMasaaki en-aut-sei=Hirai en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MuraokaYuji en-aut-sei=Muraoka en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyaTakayoshi en-aut-sei=Yokoya en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University affil-num=2 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University affil-num=3 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University affil-num=4 en-affil= kn-affil=Advanced Science Research Center, Japan Atomic Energy Agency affil-num=5 en-affil= kn-affil=Advanced Science Research Center, Japan Atomic Energy Agency affil-num=6 en-affil= kn-affil=Advanced Science Research Center, Japan Atomic Energy Agency affil-num=7 en-affil= kn-affil=Institute for Solid State Physics, The University of Tokyo affil-num=8 en-affil= kn-affil=Institute for Solid State Physics, The University of Tokyo affil-num=9 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University affil-num=10 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University affil-num=11 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University en-keyword=Electronic structure kn-keyword=Electronic structure en-keyword=Laser angle-resolved photoemission spectroscopy kn-keyword=Laser angle-resolved photoemission spectroscopy en-keyword=URu2Si2 kn-keyword=URu2Si2 en-keyword=Hidden order kn-keyword=Hidden order END start-ver=1.4 cd-journal=joma no-vol=82 cd-vols= no-issue=20 article-no= start-page=205108-1 end-page=205108-6 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=20101108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Signature of hidden order and evidence for periodicity modification in URu2Si2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The detail of electronic structures near the Fermi level in URu2Si2 has been investigated employing state-of-art laser angle-resolved photoemission spectroscopy. The observation of a narrow dispersive band near the Fermi level in the ordered state as well as its absence in a Rh-substituted sample strongly suggest that the emergence of the narrow band is a clear signature of the hidden-order transition. The temperature dependence of the narrow band, which appears at the onset of the hidden-order transition, invokes the occurrence of periodicity modification in the ordered state, which is shown for the first time by any spectroscopic probe. We compare our data to other previous studies and discuss possible implications. en-copyright= kn-copyright= en-aut-name=YoshidaRikiya en-aut-sei=Yoshida en-aut-mei=Rikiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraYoshiaki en-aut-sei=Nakamura en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuiMasaki en-aut-sei=Fukui en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HagaYoshinori en-aut-sei=Haga en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoEtsuji en-aut-sei=Yamamoto en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnukiYoshichika en-aut-sei=Onuki en-aut-mei=Yoshichika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkawaMario en-aut-sei=Okawa en-aut-mei=Mario kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShinShik en-aut-sei=Shin en-aut-mei=Shik kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraiMasaaki en-aut-sei=Hirai en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MuraokaYuji en-aut-sei=Muraoka en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyaTakayoshi en-aut-sei=Yokoya en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University affil-num=2 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University affil-num=3 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University affil-num=4 en-affil= kn-affil=Advanced Science Research Center, Japan Atomic Energy Agency affil-num=5 en-affil= kn-affil=Advanced Science Research Center, Japan Atomic Energy Agency affil-num=6 en-affil= kn-affil=Advanced Science Research Center, Japan Atomic Energy Agency affil-num=7 en-affil= kn-affil=Institute for Solid State Physics, The University of Tokyo affil-num=8 en-affil= kn-affil=Institute for Solid State Physics, The University of Tokyo affil-num=9 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University affil-num=10 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University affil-num=11 en-affil= kn-affil=The Graduate School of Natural Science and Technology, Okayama University END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=3 article-no= start-page=213 end-page=219 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Statistical Analysis of Prognostic Factors for Survival in Patients with Spinal Metastasis en-subtitle= kn-subtitle= en-abstract= kn-abstract=There are a variety of treatment options for patients with spinal metastasis, and predicting prognosis is essential for selecting the proper treatment. The purpose of the present study was to identify the significant prognostic factors for the survival of patients with spinal metastasis. We retrospectively reviewed 143 patients with spinal metastasis. The median age was 61 years. Eleven factors reported previously were analyzed using the Cox proportional hazards model:gender, age, performance status, neurological deficits, pain, type of primary tumor, metastasis to major organs, previous chemotherapy, disease-free interval before spinal metastasis, multiple spinal metastases, and extra-spinal bone metastasis. The average survival of study patients after the first visit to our clinic was 22 months. Multivariate survival analysis demonstrated that type of primary tumor (hazard ratio [HR]＝6.80, p＜0.001), metastasis to major organs (HR＝2.01, p＝0.005), disease-free interval before spinal metastasis (HR＝1.77, p＝0.028), and extra-spinal bone metastasis (HR＝1.75, p＝0.017) were significant prognostic factors. Type of primary tumor was the most powerful prognostic factor. Other prognostic factors may differ among the types of primary tumor and may also be closely associated with primary disease activity. Further analysis of factors predicting prognosis should be conducted with respect to each type of primary tumor to help accurately predict prognosis. en-copyright= kn-copyright= en-aut-name=KataokaMasaki en-aut-sei=Kataoka en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=TakedaKen en-aut-sei=Takeda en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItaniSatoru en-aut-sei=Itani en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugimotoYoshihisa en-aut-sei=Sugimoto en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MisawaHaruo en-aut-sei=Misawa en-aut-mei=Haruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SendaMasuo en-aut-sei=Senda en-aut-mei=Masuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakaharaShinnosuke en-aut-sei=Nakahara en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil= kn-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine affil-num=2 en-affil= kn-affil=Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine affil-num=3 en-affil= kn-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine affil-num=4 en-affil= kn-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine affil-num=5 en-affil= kn-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine affil-num=6 en-affil= kn-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine affil-num=7 en-affil= kn-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine affil-num=8 en-affil= kn-affil=Department of Rehabilitation, Okayama University Hospital affil-num=9 en-affil= kn-affil=Department of Orthopaedic Surgery, Okayama Medical Center affil-num=10 en-affil= kn-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine en-keyword=spine kn-keyword=spine en-keyword=metastasis kn-keyword=metastasis en-keyword=survival kn-keyword=survival en-keyword=prognostic factor kn-keyword=prognostic factor en-keyword=cancer kn-keyword=cancer END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20120323 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=転移性脊椎腫瘍における予後予測因子の統計学的解析 kn-title=Statistical Analysis of Prognostic Factors for Survival in Patients with Spinal Metastasis en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KataokaMasaki en-aut-sei=Kataoka en-aut-mei=Masaki kn-aut-name=片岡昌樹 kn-aut-sei=片岡 kn-aut-mei=昌樹 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=48 cd-vols= no-issue=7 article-no= start-page=1585 end-page=1592 dt-received= dt-revised= dt-accepted= dt-pub-year=1936 dt-pub=19360731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Über den Einfluss der einigen Organlipoide auf die Blutgerinnung kn-title=臟器「リポイド」ノ家兎血液凝固ニ及ボス影響ニ就イテ en-subtitle= kn-subtitle= en-abstract= kn-abstract=Es ist allgemein bekannt, dass das Organextrakt einen grossen Einfluss auf die Blutgerinnung hat. Bordet u. Delange, Zack, Howell, Watanabe, Masaki, Saito, Odawara u. a. m. berichten einstimmig, dass eine die Blutgerinnung beschleunigende Substanz im Organextrakt Lipoide sind. Aber was für ein Lipoid die Blutgerinnung beschleunigt und was für ein Lipoid sie verlangsamt, daüber gehen die Meinungen in ihren Berichten auseiuander. Auf Anregung und unter Leitung unseres hochverehrten Vorstands, Herrn Prof. Dr. S. Oinuma, forschte ich dem Einfluss einiger Lipoide (Kephalin, Lezithin und Cholesterin) auf die Blutgerinnung nach. Untersuchungsmethode: Eine Modifikation im Bürkerschen Apparat. Untersuchungsmaterial: Blut; Kanincheublut. Lipoide; 1) vom Rindenblut. 2) vom Rindenhirn. Resultate: 1) Vom Rindenblut oder vom Rindenhirn extrahiertes Kephalin beschleunigt die Gerinnung des Kaninchenblutes im Prüfungsgefäss. 2) Vom Rindenhirn extrahiertes Lezithin verlangsamt die Gerinnung des Kaninchenblutes im Prüfungsgefäss. 3) Vom Rinderhirn extrahiertes Cholesterin verlangsamt die Gerinnung des Kaninchenblutes im Prüfungsgefäss. 4) Eine die Blutgerinnung beschleunigende Wirkuug des Kephalin findet sich in der gleichen Weise wie die der Thrombokinase auf die Blutgerinnung. en-copyright= kn-copyright= en-aut-name=OkamuraYosiyuki en-aut-sei=Okamura en-aut-mei=Yosiyuki kn-aut-name=岡村好幸 kn-aut-sei=岡村 kn-aut-mei=好幸 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山醫科大學生理學教室 END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=2 article-no= start-page=155 end-page=162 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Design of Hemispherical Radio Frequency (RF) Capacitive-type Electrode Free of Edge Effects for Treatment of Intracavitary Tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=A new hemispherical electrode to heat oral cavity cancer is proposed. The electrode does not produce a hot spot around its edge, a feature that usually arises when using radio frequency (RF) capacitive-type heating. The hemispherical electrode was designed by computer simulation using a 3-D finite element method. To assess its practicality and effectiveness, we built a prototype hemispherical electrode and evaluated its heating characteristics by phantom experiments. The heating effects on the phantom were measured by thermography. The concave phantom surface in contact with the hemispherical electrode showed a uniform increase in temperature, with no obvious edge effect. The proposed electrode allows non-invasive RF capacitive-type heating for intracavity tumors that was not previously considered possible, and should contribute to the multidisciplinary treatment of intracavity tumors. en-copyright= kn-copyright= en-aut-name=MoriyamaMasahiro en-aut-sei=Moriyama en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaguchiAtsuya en-aut-sei=Kawaguchi en-aut-mei=Atsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokokawaMasaki en-aut-sei=Yokokawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkedaShin en-aut-sei=Ikeda en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitagakiHajime en-aut-sei=Kitagaki en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchidaNobue en-aut-sei=Uchida en-aut-mei=Nobue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Departments of Radiation Oncology, Faculty of Medicine, Shimane University affil-num=2 en-affil= kn-affil=Departments of Radiation Oncology, Faculty of Medicine, Shimane University affil-num=3 en-affil= kn-affil=Departments of Radiation Oncology, Faculty of Medicine, Shimane University affil-num=4 en-affil= kn-affil=Departments of Radiation Oncology, Faculty of Medicine, Shimane University affil-num=5 en-affil= kn-affil=Departments of Radiology, Faculty of Medicine, Shimane University affil-num=6 en-affil= kn-affil=Departments of Radiation Oncology, Faculty of Medicine, Shimane University en-keyword=radiofrequency heating kn-keyword=radiofrequency heating en-keyword=capacitive-type heating kn-keyword=capacitive-type heating en-keyword=electrode kn-keyword=electrode en-keyword=edge effect kn-keyword=edge effect en-keyword=hemispherical electrode kn-keyword=hemispherical electrode END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=4 article-no= start-page=65 end-page=86 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20120315 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A Study on the Economic Effects of Public Debt in Japan kn-title=わが国の財政赤字　何が問題か en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HiranoMasaki en-aut-sei=Hirano en-aut-mei=Masaki kn-aut-name=平野正樹 kn-aut-sei=平野 kn-aut-mei=正樹 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=101 cd-vols= no-issue= article-no= start-page=13 end-page=18 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20120201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Possibility of Sand Culture for Melon Using Root-proof Capillary Wick in Mid-summer Period kn-title=盛夏期における防根給水ひもを用いたメロン砂栽培の可能性 en-subtitle= kn-subtitle= en-abstract=栽培期間の大半の日数が高温となる盛夏期において防根給水ひもを用いたメロン砂栽培が可能であるかどうかを検討した．処理区は，大塚A処方培養液のECを段階的に低下させて供給する培養液区，全量を肥料調節型肥料で培地に混和する肥効調節型肥料区（以下、肥料区）の2区とした．最高平均地温は34.8℃，最低平均地温は26.9℃であった．肥料区では定植2週間後の交配期に8株中5株に萎れ症状が生じたが，これは定植後～交配期において培地が高EC状態であったことが原因と考えら れた．一方で，培養液区では萎れ症状は全くみられなかった．肥料区の正常３個体と培養液区の全個体の果実重の平均は2.3 ㎏，糖度 (Brix°) は14.4であった．以上より，盛夏期における防根給水ひもを用いたメロン砂栽培は，培養液管理によって安定生産が見込めること，肥料での栽培も施肥設計を考慮すれば同期の砂栽培に適用可能であることが示唆された． kn-abstract=Effects of liquid fertilizer (LF) and controlled-release fertilizer (CRF) on growth and fruit enlargement of netted melon in 6L sand medium were investigated in a cultivation method using root-proof capillary wicks in mid-summer. Average of maximum and minimum root-zone temperatures was 34.8°Cand 26.9°C, respectively. Wilted symptoms appeared very often in 5 out of 8 plants at 2 weeks after transplanting in CRF with a high electric conductivity (EC) of medium solution. In contrast, such symptoms were not found at all in LF with a lower EC. In LF, average fruit weight was 2.3Kg and fruit Brix was 14.4, and non-wilted plants in CRF also showed the same levels as LF in weight and Brix of fruits. These results indicated the possibility of sand culture for melon in mid-summer with LF or a modified fertilizer combination design of CRF. en-copyright= kn-copyright= en-aut-name=KawaharaMasaki en-aut-sei=Kawahara en-aut-mei=Masaki kn-aut-name=川原雅規 kn-aut-sei=川原 kn-aut-mei=雅規 aut-affil-num=1 ORCID= en-aut-name=MasudaMasaharu en-aut-sei=Masuda en-aut-mei=Masaharu kn-aut-name=桝田正治 kn-aut-sei=桝田 kn-aut-mei=正治 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil=岡山大学 en-keyword=capillary watering kn-keyword=capillary watering en-keyword=liquid fertilizer kn-keyword=liquid fertilizer en-keyword=controlled-release fertilizer kn-keyword=controlled-release fertilizer en-keyword=high temperature kn-keyword=high temperature END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=2 article-no= start-page=135 end-page=140 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Heme breakdown and ischemia/reperfusion injury in grafted liver during living donor liver transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can cause early graft injury. However, the detailed mechanism of I/R injury remains unknown. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism and results in the production of iron, carbon monoxide (CO), and biliverdin IXα. Furthermore, in animals, HO-1 has a protective effect against oxidative stress associated with I/R injury. However, in humans, the molecular mechanism and clinical significance of HO-1 remain unclear. We previously demonstrated that exhaled CO levels increase during LDLT, and postulated that this may indicate I/R injury. In this study, we elucidate the origin of increased exhaled CO levels and the role of HO-1 in I/R injury during LDLT. We studied 29 LDLT donors and recipients each. For investigation of HO-1 gene expression by polymerase chain reaction and HO-1 localization by immunohistological staining, liver biopsies from the grafted liver were conducted twice, once before and once after I/R. Exhaled CO levels and HO-1 gene expression levels significantly increased after I/R. In addition, HO-1 levels significantly increased after I/R in Kupffer cells. Furthermore, we found a significant positive correlation between exhaled CO levels and HO-1 gene expression levels. These results indicated that increased heme breakdown in the grafted liver is the source of increased exhaled CO levels. We also found a significant relationship between HO-1 gene expression levels and alanine aminotransferase (ALT) levels; i.e., the higher the HO-1 gene expression levels, the higher the ALT levels. These results suggest that HO-1-mediated heme breakdown is caused by I/R during LDLT, since it is associated with increased exhaled CO levels and liver damage. en-copyright= kn-copyright= en-aut-name=MatsumiJunya en-aut-sei=Matsumi en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsusakiTakashi en-aut-sei=Matsusaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakuRyuji en-aut-sei=Kaku en-aut-mei=Ryuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimizuHiroko en-aut-sei=Shimizu en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiToru en-aut-sei=Takahashi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumiMasaki en-aut-sei=Matsumi en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaKiyoshi en-aut-sei=Morita en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School affil-num=2 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School affil-num=3 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School affil-num=5 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Faculty of Health and Welfare Science, Okayama Prefectural University affil-num=7 en-affil= kn-affil=Department of Hepato-Biliary-Pancreatic Surgery, Okayama University Medical School affil-num=8 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Department of Anesthesiology and Resuscitology, Okayama University Medical School en-keyword=ischemia/reperfusion injury kn-keyword=ischemia/reperfusion injury en-keyword=heme oxygenase kn-keyword=heme oxygenase en-keyword=liver damage kn-keyword=liver damage en-keyword=living donor liver transplantation kn-keyword=living donor liver transplantation END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=3 article-no= start-page=29 end-page=48 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20111201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A Study on the Expansion of Public Expenditure in Japan kn-title=わが国の財政支出の拡大について考える en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HiranoMasaki en-aut-sei=Hirano en-aut-mei=Masaki kn-aut-name=平野正樹 kn-aut-sei=平野 kn-aut-mei=正樹 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=123 cd-vols= no-issue=3 article-no= start-page=213 end-page=216 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20111201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Significance of reduction surgery in multidisciplinary treatment of advanced hepatocellular carcinoma with multiple intrahepatic metastases : A case report kn-title=多発肝内転移を伴う進行肝細胞癌に対して減量手術を含めた集学的治療が奏功した一例 en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a case of advanced HCC with multiple intrahepatic metastases who obtained long-term survival by reductive hepatic resection as part of a multidisciplinary treatment. The patient was a 75-year-old man who had HCC, 13.5 cm in diameter in the right lobe of the liver with multiple intrahepatic metastases around the main tumor and 7 intrahepatic metastases in the left lobe of the liver. The large main tumor and intrahepatic metastases around the main tumor were initially resected by right lobectomy as reduction surgery. Transcatheter arterial chemoembolization (TACE) with epirubicin for intrahepatic metastases in the remnant liver was started 1 month after initial hepatectomy and repeated every 3 months. Twelve months after initial hepatectomy, lung metastases appeared, so we started systemic chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP). In addition, we changed epirubicin to CDDP for TACE. Despite this combination therapy, 20 months after the initial hepatectomy, the lung metastases showed an increase in size. We decided to discontinue systemic chemotherapy and administer sorafenib. The patient was alive without progression of intrahepatic metastasis and lung metastasis more than 26 months after the initial hepatectomy. en-copyright= kn-copyright= en-aut-name=SatohDaisuke en-aut-sei=Satoh en-aut-mei=Daisuke kn-aut-name=佐藤太祐 kn-aut-sei=佐藤 kn-aut-mei=太祐 aut-affil-num=1 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name=八木孝仁 kn-aut-sei=八木 kn-aut-mei=孝仁 aut-affil-num=2 ORCID= en-aut-name=SadamoriHiroshi en-aut-sei=Sadamori en-aut-mei=Hiroshi kn-aut-name=貞森裕 kn-aut-sei=貞森 kn-aut-mei=裕 aut-affil-num=3 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name=楳田祐三 kn-aut-sei=楳田 kn-aut-mei=祐三 aut-affil-num=4 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name=藤原俊義 kn-aut-sei=藤原 kn-aut-mei=俊義 aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学 affil-num=4 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学 affil-num=5 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　消化器外科学 en-keyword=進行肝細胞癌 (advanced hepatocellular carcinoma) kn-keyword=進行肝細胞癌 (advanced hepatocellular carcinoma) en-keyword=減量手術 (reduction surgery) kn-keyword=減量手術 (reduction surgery) en-keyword=肝動脈塞栓療法 (transcatheter arterial chemoembolization : TACE) kn-keyword=肝動脈塞栓療法 (transcatheter arterial chemoembolization : TACE) en-keyword=ソラフェニブ (sorafenib) kn-keyword=ソラフェニブ (sorafenib) en-keyword=集学的治療 (multidisciplinary treatment) kn-keyword=集学的治療 (multidisciplinary treatment) END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=2 article-no= start-page=51 end-page=60 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=200203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Regulatory Role for Complement Receptors (CD21/CD35) in the Recombination Activating Gene Expression in Mouse Peripheral B Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=A population of peripheral B cells have been shown to express recombination activating gene products, RAG-1 and RAG-2, which are considered to be involved in revising the B cell antigen receptor (BCR) in the periphery. BCR engagement has been reported to turn off RAG expression in peripheral B cells, whereas the same treatment has an opposite effect in immature B cells in the bone marrow. In contrast to receptor editing that is involved in the removal of autoreactivity in immature B cells, it has been shown that secondary V(D)J rearrangement in peripheral B cells, termed receptor revision, contributes to affinity maturation of antibodies. Here, we show that RAG-2 expression in murine splenic B cells was abrogated by the coligation of BCR with complement receptors (CD21/CD35) much more efficiently than by the engagement of BCR alone. On the other hand, the same coligation augmented proliferation of anti-CD40-stimulated B cells. Consistent with these observations, RAG-2 expression was lower in the draining lymph nodes of the quasi-monoclonal mice when they were immunized with a high-affinity antigen than with a low-affinity one. These findings suggest a crucial role for CD21/CD35 in directing the conservation or the revision of BCRs in peripheral B cells. en-copyright= kn-copyright= en-aut-name=HikidaMasaki en-aut-sei=Hikida en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=NakayamaYasunori en-aut-sei=Nakayama en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanayamaNaoki en-aut-sei=Kanayama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhmoriHitoshi en-aut-sei=Ohmori en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University affil-num=2 en-affil= kn-affil=Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University affil-num=3 en-affil= kn-affil=Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University affil-num=4 en-affil= kn-affil=Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University affil-num=5 en-affil= kn-affil=Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=1-2 article-no= start-page=91 end-page=96 dt-received= dt-revised= dt-accepted= dt-pub-year=2004 dt-pub=200403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Generation of IgM and IgG1 monoclonal antibodies with identical variable regions: comparison of avidity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Generally, IgM antibodies (Abs) produced in a primary immune response show lower affinity for an inducing antigen (Ag) compared with the corresponding IgG Abs that are major switched isotypes formed in the secondary response. An IgM molecule is a pentamer with 10 Ag-binding sites that will contribute to an increase of avidity for an Ag. To estimate the contribution of the pentameric structure to the avidity of an IgM Ab, we generated IgM and IgG1 monoclonal Abs (mAbs) with identical V regions that are specific for 4-hydroxy-3-nitrophenylacetyl (NP) by in vitro class switching of B cells followed by the cell fusion with a mouse myeloma cell line. Compared with an anti-NP IgG1 mAb, the corresponding IgM mAb showed much higher avidity for NP-conjugated bovine serum albumin, which was drastically reduced after being dissociated into monomers. en-copyright= kn-copyright= en-aut-name=KanayamaNaoki en-aut-sei=Kanayama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamakoshiKimi en-aut-sei=Yamakoshi en-aut-mei=Kimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KiyomiMasaaki en-aut-sei=Kiyomi en-aut-mei=Masaaki 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=OhmoriHitoshi en-aut-sei=Ohmori en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University affil-num=2 en-affil= kn-affil=Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University affil-num=3 en-affil= kn-affil=Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University affil-num=4 en-affil= kn-affil=Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University affil-num=5 en-affil= kn-affil=Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University END start-ver=1.4 cd-journal=joma no-vol=100 cd-vols= no-issue= article-no= start-page=39 end-page=51 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20110201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=エジプト紅海沿岸のマングローブ林の林分構造 kn-title=Forest structure of gray mangrove (Avicennia marina) along Egyptian Red Sea coast en-subtitle= kn-subtitle= en-abstract= kn-abstract=Established mangrove forests along the coastal area of the Arabian Peninsula and African side of the Red Sea are uniquely different from mangrove forests in other parts of the world because of their low biodiversity and harsh habitat of arid and highly saline conditions. Therefore mangrove forests in this area appear in patchy and scattered patterns at mouths of wadi or in sheltered lagoons with rare and irregular flooding. Most of them are pure forests of Avicennia marina, occasionally mixed with Rhizophora mucronata in the southern part of the Red Sea. In this study, we analyze the forest structure of A. marina and discuss the regeneration strategy and the forest dynamics of this unique mangrove species. Three experimental plots of 1000 to 2000 trees/ha were selected from north to south along the Red Sea coast. The highest tree size (6.8m) suggested severe effects of the high salinity of the Red Sea (3.2 to 4.9%) on tree growth. Dense mantle vegetation had developed at the forest edge facing the open sea to protect the forest interior against strong waves and wind. Tree growth was also prevented by severe drought on the landside edge of the forest. All the forests had a dense seedling bank throughout the forest floor, with a very high rate of turnover and regeneration, which seldom occurred in other forests. en-copyright= kn-copyright= en-aut-name=YoshikawaKen en-aut-sei=Yoshikawa en-aut-mei=Ken kn-aut-name=吉川賢 kn-aut-sei=吉川 kn-aut-mei=賢 aut-affil-num=1 ORCID= en-aut-name=InoueMasaki en-aut-sei=Inoue en-aut-mei=Masaki kn-aut-name=井上正樹 kn-aut-sei=井上 kn-aut-mei=正樹 aut-affil-num=2 ORCID= en-aut-name=YoshimoriIchidou en-aut-sei=Yoshimori en-aut-mei=Ichidou kn-aut-name=吉森一道 kn-aut-sei=吉森 kn-aut-mei=一道 aut-affil-num=3 ORCID= en-aut-name=NakashimaAtsushi en-aut-sei=Nakashima en-aut-mei=Atsushi kn-aut-name=中島敦司 kn-aut-sei=中島 kn-aut-mei=敦司 aut-affil-num=4 ORCID= en-aut-name=TeraminamiTomohiro en-aut-sei=Teraminami en-aut-mei=Tomohiro kn-aut-name=寺南智弘 kn-aut-sei=寺南 kn-aut-mei=智弘 aut-affil-num=5 ORCID= en-aut-name=MatsuoNaoko en-aut-sei=Matsuo en-aut-mei=Naoko kn-aut-name=松尾奈緒子 kn-aut-sei=松尾 kn-aut-mei=奈緒子 aut-affil-num=6 ORCID= en-aut-name=BanjoRyo en-aut-sei=Banjo en-aut-mei=Ryo kn-aut-name=萬城遼 kn-aut-sei=萬城 kn-aut-mei=遼 aut-affil-num=7 ORCID= en-aut-name=MiyamotoChiharu en-aut-sei=Miyamoto en-aut-mei=Chiharu kn-aut-name=宮本千晴 kn-aut-sei=宮本 kn-aut-mei=千晴 aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Graduate School of Environmental Science, Okayama University affil-num=2 en-affil= kn-affil=Faculty of Agriculture, Okayama University affil-num=3 en-affil= kn-affil=Faculty of Agriculture, Okayama University affil-num=4 en-affil= kn-affil=Graduate School of Systems Engineering, Wakayama University affil-num=5 en-affil= kn-affil=Graduate School of Systems Engineering, Wakayama University affil-num=6 en-affil= kn-affil=Graduate School of Bioresources, Mie University affil-num=7 en-affil= kn-affil=Faculty of Bioresources, Mie University affil-num=8 en-affil= kn-affil=NGO, Action for Mangrove Reforestation en-keyword=Gray mangrove (Avicennia marina) kn-keyword=Gray mangrove (Avicennia marina) en-keyword=the Red Sea kn-keyword=the Red Sea en-keyword=forest structure kn-keyword=forest structure en-keyword=seedling bank kn-keyword=seedling bank END start-ver=1.4 cd-journal=joma no-vol=100 cd-vols= no-issue= article-no= start-page=9 end-page=15 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20110201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Application of Controlled-release Fertilizer to Netted Melon Cultivation Using Root-proof Capillary Wick kn-title=ネットメロンの防根給水ひも栽培における肥効調節型肥料の適用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Use of controlled-release fertilizer in limited amount of soil and sand medium for netted melon cultivation using a root-proof capillary wick was investigated. The first experiment consisted of 3 lots of soil medium. 1) 3L medium used throughout the cultivation period (A); 2) 6L medium used throughout the cultivation period (B); 3) 3L used until pollination stage, then a partitioning board removed to increase the growth medium to 6L (C). Average of one fruit weight was 1.4 kg in A and B, but only 1.2 kg in C. Brix° value was 13.1 in A, 13.6 in B and 13.4 in C, respectively. The stem diameter at the time of pollination was largest in B in which there was fruit cracking that was also observed in C, but not in A. The root dry weight was highest in A. These results indicate that the restricted medium of 3L presents a potential for good fruit production. The second experiment consisted of 4 lots with 3L medium each: 1) soil and fertilizer medium as in experiment 1; 2) sand and fertilizer medium as in lot 1); 3) sand and slower release fertilizer; 4) sand and half of fertilizer at planting and an additional fertilizer bag placed on the wick at time of pollination. Although cracking fruits occurred 75% in 3) and 37.5% in 4), there was no cracking of fruits in 1) and 2), in which fruit weight in the latter was 1.5kg and brix° value of 14.5 was obtained. These results indicate that controlled-release fertilizer is useful for fruit production of netted melon in sand medium of 3L with a high potential for reuse. en-copyright= kn-copyright= en-aut-name=KawaharaMasaki en-aut-sei=Kawahara en-aut-mei=Masaki kn-aut-name=川原雅規 kn-aut-sei=川原 kn-aut-mei=雅規 aut-affil-num=1 ORCID= en-aut-name=MurakamiSayo en-aut-sei=Murakami en-aut-mei=Sayo kn-aut-name=村上紗代 kn-aut-sei=村上 kn-aut-mei=紗代 aut-affil-num=2 ORCID= en-aut-name=MasudaMasaharu en-aut-sei=Masuda en-aut-mei=Masaharu kn-aut-name=桝田正治 kn-aut-sei=桝田 kn-aut-mei=正治 aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=応用植物科学コース affil-num=2 en-affil= kn-affil=応用植物科学コース affil-num=3 en-affil= kn-affil=応用植物科学コース en-keyword=medium volume kn-keyword=medium volume en-keyword=sand medium kn-keyword=sand medium en-keyword=fruit yield kn-keyword=fruit yield en-keyword=cracking fruit kn-keyword=cracking fruit END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=8 article-no= start-page=2203 end-page=2216 dt-received= dt-revised= dt-accepted= dt-pub-year=1957 dt-pub=19570830 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Effects of Sympathetic Interception on the Bone Marrow Part III. Femur Bone Marrow Culture in Fluid Medium after the unilateral lumbar Sympathectomy on Rabbits kn-title=交感神経遮断の骨髓に及ぼす影響 第3編 骨髄体外液体培養法による研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Increase rates of erythrocytes and of heomoglobine of the rabbit's femur bone marrow on every 3rd., 5th, 10th, 20th, 30th and 60th days affer the unilateral Iumbar sympa the ctomy in fluid medium culture were examined. The results obtained were as follows:- (1) The maximum increase rate of erythrocytes did not occur till 5th or 10th day after the denervation, and the value fell progressively till 60th day. (2) The rate of hemoglobine showed its maximum on the 3rd. or 5th day after the operation, then decreased till both day, in which showed very little differences between both sides. (3) In most cases, increase rates of erythrocytes and of hemoglobine did not exceed over 20 percents. In concusion. the sympathetic denervation promotes the function of rabbit's bone marrow, but it only lasts a short while. This may have been due to the inerease of blood flow in the bone marrow, and secondarily it caused the hyperfunction of the bone marrow. en-copyright= kn-copyright= en-aut-name=NagaseMasaki en-aut-sei=Nagase en-aut-mei=Masaki kn-aut-name=永瀬正己 kn-aut-sei=永瀬 kn-aut-mei=正己 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部平木内科教室 END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=8 article-no= start-page=2191 end-page=2201 dt-received= dt-revised= dt-accepted= dt-pub-year=1957 dt-pub=19570830 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Effects of Sympathetic Interception on the Bone Marrow Part II. Respiration and anaerobe Glycolysis of Femur Bone Marrow after the unilateral lumbar Sympathectomy on Rabbits kn-title=交感神経遮断の骨髓に及ぼす影響 第2編 骨髄の呼吸解糖作用測定に依る研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Respiration and anaerobe glycolysis of femur bone marrows of unilateral sympathectomized rabbits were compaired with each other side on the following 3, 5, 10, 20, 30 & 120 days after the operation with the direct method of the Warburg constant volume respirometer. The results obtained were as follows: 1) The respiration (Q(O(2))) showed no remarkable differencs between each other. 2) The anaerobe glycolysis (Q(M)(N(2))) showed significant value on the operated side in 5th, 10th and 20th day groups after the operation, but transitory. So the interception of the sympathetic in rabbits promotes the function of the bone marrow. In the other word the sympathetic reduces the function of the bone marrow. en-copyright= kn-copyright= en-aut-name=NagaseMasaki en-aut-sei=Nagase en-aut-mei=Masaki kn-aut-name=永瀬正己 kn-aut-sei=永瀬 kn-aut-mei=正己 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部平木内科教室 END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=8 article-no= start-page=2175 end-page=2190 dt-received= dt-revised= dt-accepted= dt-pub-year=1957 dt-pub=19570830 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Effects of Sympathetic Interception on the Bone Marrow Part. I. Cultures in Coverships of Femur Bone Marrow after the unilateral lumbar Sympathectomy kn-title=交感神経遮断の骨髓に及ぼす影響 第1編 骨髄被覆培養法に依る研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cultures in coverslips of femur bone marrows of unilateral sympathectomized rabbits were compaired with each other side on the following 3, 5, 10, 15, 20, 30 and 90 days. The results obtained were as follows: (1) The wandering velocity of neutrophils of bone marrow of the sympathectomized side is larger than the another side, especially on the 5 th day after the operation. (2) The relative growth rate is larger than the other non-operated side on the 5 th and 10 th days after the operation. (3) The cell dencity is strikingly larger in the sympathectomized side on its 3rd, 5th, 10 th and 30th day groups after the operation. (4) Each figures show the maximum on about 5th day group after the operation, and after 30 days the results did not appear to differ between both sides, and these effects are transitory. Thus the interception of the sympathetic in rabbits promotes the function of the bone marrow transitorily. In other words the sympathetic reduces the function of the bone marrow. en-copyright= kn-copyright= en-aut-name=NagaseMasaki en-aut-sei=Nagase en-aut-mei=Masaki kn-aut-name=永瀬正己 kn-aut-sei=永瀬 kn-aut-mei=正己 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部平木内科教室 END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue=3 article-no= start-page=13 end-page=44 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=20101225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A Study on the Priority of Public Policy in Local Government kn-title=地方自治体における施策の優先順位に関する一考察−中四国地域の主要自治体からのアンケート調査結果による− en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HiranoMasaki en-aut-sei=Hirano en-aut-mei=Masaki kn-aut-name=平野正樹 kn-aut-sei=平野 kn-aut-mei=正樹 aut-affil-num=1 ORCID= en-aut-name=TaniguchiKeizo en-aut-sei=Taniguchi en-aut-mei=Keizo kn-aut-name=谷口圭三 kn-aut-sei=谷口 kn-aut-mei=圭三 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 affil-num=2 en-affil= kn-affil= END