start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=11550 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pseudohypoxia induced by iron chelators preserves working memory performance in aged mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pseudohypoxia refers to a physiological condition wherein hypoxia-inducible factor (HIF) is pharmacologically upregulated under normoxia, thereby modulating immune responses. We hypothesized that pseudohypoxia, induced by iron chelators, may similarly potentiate systemic immune responses in aged mice, concurrently triggering neuro-regenerative signaling pathways and enhancing cognitive performance. In this study, aged mice (43?48 weeks old) were orally administered two iron chelators, Super Polyphenol 10 (SP10) or Roxadustat, to induce a pseudohypoxia. An 8-week oral regimen of SP10 and Roxadustat significantly preserved working memory, as assessed by the Y-maze test (YMT). White blood cell counts and hippocampal volume, as assessed by magnetic resonance imaging (MRI), were elevated in the treatment groups relative to controls. Pseudohypoxia induced by SP10 tended to enhance neuro-regenerative signaling, specifically involving the Tau and JNK pathways, and potentially modulated Doublecortin (DCX) expression, although statistical significance was limited by sample size. Importantly, inflammatory markers, such as ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), were not elevated by treatment. Collectively, these findings suggest that pseudohypoxia induced by iron chelators preserves working memory performance accompanied by leukocytosis, without concomitant neuroinflammation. en-copyright= kn-copyright= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KasaiTomonari en-aut-sei=Kasai en-aut-mei=Tomonari 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=KomakiShiho en-aut-sei=Komaki en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HamadaYusuke en-aut-sei=Hamada en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Health Service Section, Environment Health & Safety Intelligence Department, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Energy, Graduate School of Engineering, Nagoya University kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Hypoxia-inducible factor kn-keyword=Hypoxia-inducible factor en-keyword=Working memory kn-keyword=Working memory en-keyword=Hippocampus kn-keyword=Hippocampus en-keyword=Iron kn-keyword=Iron END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=4 article-no= start-page=1769 end-page=1784 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=P53-armed Oncolytic Adenovirus Enhances the Efficacy of PD-1 Blockade in Neuroblastoma by Inducing Immunogenic Cell Death en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. Although immunotherapy with immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) has emerged as novel antitumor therapy, high-risk NB tumors are refractory to ICI therapy. Oncolytic virotherapy is expected to potentiate the antitumor immune response by inducing immunogenic cell death (ICD). In the present study, we assessed the therapeutic potential of OBP-301 and OBP-702, telomerase-specific oncolytic adenoviruses, for the induction of ICD and combined effect with PD-1 blockade against NB cells.
Materials and Methods: The cytopathic activity of OBP-301 and OBP-702 was assessed using three human MYCN-amplified NB cell lines (IMR-32, LA-N-5, and NB-1) and a murine non-MYCN-amplified NB cell line (Neuro-2a). Virus-mediated antitumor effect was assessed by analyzing cell viability, secretion of extracellular adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1), apoptosis, autophagy, and PD-L1 levels. A subcutaneous Neuro-2a tumor model was used to evaluate the in vivo antitumor effect of combination therapy with OBP-702 and anti-PD-1 antibody.
Results: OBP-702 exhibited stronger cytopathic activity, inducing ICD with secretion of ATP and HMGB1, compared to OBP-301 in human and murine NB cells. OBP-301 and OBP-702 increased apoptosis, autophagy, and PD-L1 expression in murine NB cells. Moreover, OBP-702 significantly prolonged the survival of tumor-bearing mice compared to monotherapy with PD-1 blockade.
Conclusion: OBP-702 is a promising antitumor strategy to promote the antitumor effect of ICIs by inducing ICD against NB tumors. en-copyright= kn-copyright= en-aut-name=TANIMORIMICHI en-aut-sei=TANI en-aut-mei=MORIMICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TAZAWAHIROSHI en-aut-sei=TAZAWA en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TANIMOTOTERUTAKA en-aut-sei=TANIMOTO en-aut-mei=TERUTAKA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NOUSOHIROSHI en-aut-sei=NOUSO en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WATANABEHINAKO en-aut-sei=WATANABE en-aut-mei=HINAKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OYAMATAKANORI en-aut-sei=OYAMA en-aut-mei=TAKANORI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=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=NODATAKUO en-aut-sei=NODA en-aut-mei=TAKUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Pediatric 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 Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Oncolys BioPharma, Inc. 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 Pediatric 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= en-keyword=Neuroblastoma kn-keyword=Neuroblastoma en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=p53 kn-keyword=p53 en-keyword=immunogenic cell death kn-keyword=immunogenic cell death en-keyword=PD-1 kn-keyword=PD-1 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e202501237 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Informatics]Driven and Automated Optimization in Flow Electrochemical Synthesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Electrochemical synthesis has emerged as a powerful platform for environmentally sustainable chemical transformations. When integrated with flow chemistry, electrosynthetic processes exhibit enhanced scalability, making them suitable for industrial applications. Recently, the integration of electrochemical flow systems with informatics techniques has accelerated the optimization of reaction conditions. Data-driven strategies facilitate rapid exploration of multidimensional parameter spaces, enabling identification of optimal reaction conditions with high efficiency. These advances have enabled the development of automated optimization systems. This review highlights recent progress in combining electrosynthesis, flow chemistry, and computational tools, focusing on representative examples that illustrate efficient optimization protocols and autonomous reaction development. By showcasing these developments, we discuss how the integration of these technologies is driving innovation in electrochemical synthesis. en-copyright= kn-copyright= en-aut-name=SatoEisuke en-aut-sei=Sato en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaniAkine en-aut-sei=Tani en-aut-mei=Akine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakahamaTomohiro en-aut-sei=Nakahama en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsudoKoichi en-aut-sei=Mitsudo en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=electrochemical synthesis kn-keyword=electrochemical synthesis en-keyword=flow synthesis kn-keyword=flow synthesis en-keyword=laboratory automation kn-keyword=laboratory automation END start-ver=1.4 cd-journal=joma no-vol=380 cd-vols= no-issue= article-no= start-page=114924 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Constitutive activation of MC1R in the large-billed crow (Corvus macrorhynchos) and its potential role in black plumage en-subtitle= kn-subtitle= en-abstract= kn-abstract=Melanin-based plumage coloration in birds is largely regulated by the melanocortin 1 receptor (MC1R), a G protein?coupled receptor that promotes eumelanin synthesis via cAMP signaling. In domestic chickens, constitutively activating mutations such as the MC1R^E (E92K) allele cause melanistic phenotypes, demonstrating that persistent MC1R activation can drive generalized darkening. However, to our knowledge, no experimental study has directly demonstrated constitutive MC1R activation in wild birds exhibiting uniformly black plumage. We investigated the sequence and signaling properties of MC1R from the Large-billed Crow (Corvus macrorhynchos), a species with strongly eumelanin-dominant plumage. Crow MC1R exhibited elevated basal cAMP signaling and minimal responsiveness to ƒ¿-melanocyte-stimulating hormone (ƒ¿-MSH) in both stable Chinese hamster ovary (CHO-K1) cells and transient CRE-luciferase assays in HEK293T cells, demonstrating ligand-independent activation comparable to that observed in the melanizing chicken MC1R^E (E92K) allele. Comparative sequence analysis identified multiple substitutions conserved across Corvus species. Among these, E12K and E18K were functionally evaluated based on prior associations with melanism in other birds. Although E12K modestly increased basal signaling in chicken MC1R, E18K alone or in combination with E12K did not reproduce crow-level constitutive activity, and reciprocal substitutions in crow MC1R failed to abolish ligand-independent activation. These findings demonstrate that crow MC1R possesses constitutive activity and suggest that this phenotype reflects lineage-specific modifications rather than a single activating substitution. Our results provide experimental evidence that constitutive MC1R activation is a plausible molecular mechanism that may contribute to the black plumage in the Large-billed Crow, although a direct causal relationship remains to be established. en-copyright= kn-copyright= en-aut-name=NakanoSaya en-aut-sei=Nakano en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TashiroYuichi en-aut-sei=Tashiro en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuchiHibiki en-aut-sei=Fukuchi en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AizawaSayaka en-aut-sei=Aizawa en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakeuchiSakae en-aut-sei=Takeuchi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=MC1R kn-keyword=MC1R en-keyword=Constitutive activation kn-keyword=Constitutive activation en-keyword=Ligand-independent signaling kn-keyword=Ligand-independent signaling en-keyword=Melanism kn-keyword=Melanism en-keyword=Plumage coloration kn-keyword=Plumage coloration en-keyword=Corvus macrorhynchos kn-keyword=Corvus macrorhynchos END start-ver=1.4 cd-journal=joma no-vol=264 cd-vols= no-issue= article-no= start-page=128798 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Improving thermal stability of a microcavity emitter for utilization under atmospheric environment en-subtitle= kn-subtitle= en-abstract= kn-abstract=With the development of micro-fabrication technology, various metamaterials with controlled emission spectra have been proposed as thermal emitters. However, general metamaterials have a risk of deformations and degradation at high temperatures in atmospheric conditions, which is inconvenient for use as a thermal emitter. In this study, we propose a concept to enhance the thermal durability of microcavity-type metamaterials. Although typical microcavities are entirely composed of metal to excite the resonance of electromagnetic waves, we assessed the feasibility of a microcavity consisting of silicon with minimal metal coatings. While usual metals are oxidized at high temperatures, gold is rarely oxidized due to its chemical stability. However, the gold layer deposited on the Si substrate has the potential to melt below 400 ‹C due to the formation of an Au-Si eutectic alloy, which has a much lower melting point than pure gold. Therefore, we focused on the gold-tungsten bilayer as a suitable metal coating for the silicon microcavity, thereby preventing oxidation and melting that would otherwise influence the emission spectra of the thermal emitter. The numerical analysis ensured that the proposed microcavity exhibited electromagnetic resonance, similar to that of a microcavity entirely composed of metal, unless the metal coating was too thin. The fabricated microcavity with the gold-tungsten coating also exhibited a thermal emission within a limited wavelength range, due to the microcavity resonance. Moreover, the heating experiment revealed that the microcavity with a gold-tungsten coating maintained its emissivity even when heated to 400 ‹C, which is higher than the oxidation point of tungsten and the melting point of the Au-Si eutectic alloy. Consequently, the gold-tungsten coating would be a reasonable approach to improve the stability of the microcavity-type metamaterial at high temperatures under oxidative conditions. en-copyright= kn-copyright= en-aut-name=IsobeKazuma en-aut-sei=Isobe en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorishigeShota en-aut-sei=Morishige en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoTaiyo en-aut-sei=Sato en-aut-mei=Taiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaYutaka en-aut-sei=Yamada en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoribeAkihiko en-aut-sei=Horibe en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Metamaterial kn-keyword=Metamaterial en-keyword=Microcavity emitter kn-keyword=Microcavity emitter en-keyword=Emissivity spectrum kn-keyword=Emissivity spectrum en-keyword=Thermal stability kn-keyword=Thermal stability en-keyword=Tungsten oxidation kn-keyword=Tungsten oxidation en-keyword=Eutectic melting kn-keyword=Eutectic melting END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=4 article-no= start-page=115137 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multifaceted role of POU5F1P1 in regulating its parental stem cell gene, POU5F1 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The human-specific retrogene POU5F1P1 (OCT4-Pseudogene1; OCT4-PG1), derived from stem cell factor POU5F1 (OCT4A), is predicted to encode an OCT4A-like protein; however, its function remains unclear. This study investigated OCT4-PG1 expression, translational control, and its role in endometrial cancer and stem cell regulation. Quantitative analyses revealed that elevated OCT4A, but not OCT4-PG1, expression correlated with clinical risk factors associated with poor prognosis in patients with endometrial cancer. OCT4-PG1 is under strong translational suppression mediated by its untranslated region and does not function as a protein under normal conditions. Instead, it acts as a non-coding RNA that suppresses OCT4A translation. Structural analyses showed that a single amino acid deletion (Gln259) destabilizes the OCT4-PG1 protein, thereby preventing its tumorigenic and transcriptional functions. Nevertheless, OCT4-PG1 forms heterodimers with OCT4A or SOX2, enhancing the regulatory activity of OCT4A. These findings highlight the regulatory role of pseudogenes in cancer and stem cell biology, with implications for therapies targeting OCT4A-related pathways. en-copyright= kn-copyright= en-aut-name=IrieKyohei en-aut-sei=Irie en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KosakaMitsuko en-aut-sei=Kosaka en-aut-mei=Mitsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MizunoNobuhiko en-aut-sei=Mizuno en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OmaeRyo en-aut-sei=Omae en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataniYoshimasa en-aut-sei=Nakatani en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OoSandi Myat Noe en-aut-sei=Oo en-aut-mei=Sandi Myat Noe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaguchiAyano en-aut-sei=Kawaguchi en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=bio062463 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gap junction-mediated signaling coordinates Rhodopsin coupling for Drosophila color vision en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Drosophila compound eye is composed of approximately 800 ommatidia, and every ommatidium contains eight photoreceptor cells, six outer cells (R1-R6) and two inner cells (R7 and R8), and accessory cells (cone and pigment cells). The expression of rhodopsin genes in R7 and R8 is highly coordinated through an instructive signal from R7 to R8. The activity of the homeodomain protein Defective proventriculus in R1 is also required to transmit this instructive signal, suggesting that cell?cell communication between R7, R1, and R8 is important to generate the pattern of Rh expression in R7/R8 (Rhodopsin coupling). As cell junctions play crucial roles in maintaining the structural and functional integrity of tissues, we tested whether cell junction proteins are involved in the interactions between photoreceptor cells. Here, we demonstrate that gap junction proteins innexin 2 and innexin 7 in accessory cells are necessary for transmitting signals from R7 to R8. In addition, Notch-mediated accessory cell development and Rhodopsin coupling in R7/R8 are highly correlated. Our results provide evidence that functional coupling of two different neurons, R7 and R8, is established through gap junction-mediated signaling from adjacent accessory cells. en-copyright= kn-copyright= en-aut-name=ZhangXuanshuo en-aut-sei=Zhang en-aut-mei=Xuanshuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShinjoRyoki en-aut-sei=Shinjo en-aut-mei=Ryoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitamataManabu en-aut-sei=Kitamata en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsuneShinichi en-aut-sei=Otsune en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakagoshiHideki en-aut-sei=Nakagoshi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Division of Health Science, Advanced Comprehensive Research Organization, Teikyo University kn-affil= affil-num=4 en-affil=Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Division of Biological Sciences, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Drosophila kn-keyword=Drosophila en-keyword=Eye kn-keyword=Eye en-keyword=Gap junction kn-keyword=Gap junction en-keyword=Innexin kn-keyword=Innexin en-keyword=Opsin kn-keyword=Opsin END start-ver=1.4 cd-journal=joma no-vol=179 cd-vols= no-issue= article-no= start-page=156034 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Visible-light-induced photocatalytic intermolecular cyclization for synthesis of 2,2-diarylchromanes en-subtitle= kn-subtitle= en-abstract= kn-abstract=The photocatalytic cyclization of salicylaldehydes with 1,1-diarylalkenes for the synthesis of 2,2-diarylchromanes has been developed. The catalytic amount of Ir photocatalyst proceeds the cyclization to give the various 2,2-diaryl chromanes under irradiation with blue LEDs. The obtained 2,2-diarylchromanes exhibit noticeable free-radical-scavenging activities, which have been largely unexplored. Notably, the chromane can convert to 2,2-diaryl-2H-naphtho[1,2-b]pyran bearing strong electron withdrawing groups, which are found in various photochromic materials. Thus, the present reaction constitutes a promising tool for the synthesis of functional materials and biologically active compounds. en-copyright= kn-copyright= en-aut-name=KodakiSakura en-aut-sei=Kodaki en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoMomo en-aut-sei=Kondo en-aut-mei=Momo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MinatoJunta en-aut-sei=Minato en-aut-mei=Junta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItakuraShoko en-aut-sei=Itakura en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakamuraHiroyoshi en-aut-sei=Takamura en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishikawaMakiya en-aut-sei=Nishikawa en-aut-mei=Makiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KadotaIsao en-aut-sei=Kadota en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KusamoriKosuke en-aut-sei=Kusamori en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaKenta en-aut-sei=Tanaka en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science kn-affil= affil-num=3 en-affil=Laboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of Science kn-affil= affil-num=4 en-affil=Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Laboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of Science kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=Chromane kn-keyword=Chromane en-keyword=Visible light kn-keyword=Visible light en-keyword=Photocatalysis kn-keyword=Photocatalysis en-keyword=Chromene kn-keyword=Chromene en-keyword=Free-radical-scavenging activity kn-keyword=Free-radical-scavenging activity END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=5 article-no= start-page=2308 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Aerobic Exercise Attenuates Epidermal Hyperplasia in an Obesity-Associated Psoriasiform Dermatitis Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Obesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice were fed a high-fat diet (HFD) for 7 weeks to induce obesity and subsequently underwent moderate-intensity treadmill running for 3 weeks. Psoriasiform dermatitis was induced by daily topical application of imiquimod (IMQ) to the skin for five consecutive days. HFD increased body weight, epididymal fat mass, and serum cholesterol. HFD-fed mice developed more severe IMQ-induced psoriatic skin changes compared with normal diet-fed mice. Treadmill exercise modestly reduced body weight gain and attenuated epidermal hyperplasia in HFD-fed mice. In contrast, inflammatory cytokine expression, including Tnfa, Il17a, and Il23a, showed modest increases in the skin of HFD-fed exercised mice, which did not parallel the improvement in epidermal hyperplasia. Overall, these findings indicate that while obesity exacerbates psoriasiform dermatitis, aerobic exercise ameliorates epidermal hyperplasia in obese mice without corresponding changes in inflammatory cytokine expression in the skin, suggesting that exercise may influence psoriatic skin changes through multiple metabolic and immunological pathways. en-copyright= kn-copyright= en-aut-name=MatsudaYoshihiro en-aut-sei=Matsuda en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakezakiDaiki en-aut-sei=Takezaki en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoYuma en-aut-sei=Sakamoto en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BabaNobuyasu en-aut-sei=Baba en-aut-mei=Nobuyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IsekiMasanori en-aut-sei=Iseki en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawakamiYoshio en-aut-sei=Kawakami en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShiomiTatsushi en-aut-sei=Shiomi en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MukaiTomoyuki en-aut-sei=Mukai en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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 Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Kawasaki Medical School kn-affil= affil-num=9 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= en-keyword=psoriasis kn-keyword=psoriasis en-keyword=obesity kn-keyword=obesity en-keyword=aerobic exercise kn-keyword=aerobic exercise en-keyword=imiquimod kn-keyword=imiquimod en-keyword=high-fat diet kn-keyword=high-fat diet END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=2 article-no= start-page=364 end-page=370 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Functional Transport Properties of Human Zinc Transporter 1: Kinetics and pH-Dependency en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intracellular zinc (Zn2+) homeostasis is essential for physiological and pathological processes and is strictly regulated by Zn2+ transporters. Zinc transporter 1 (ZnT1) is a ubiquitously expressed plasma membrane-localized Zn transporter that exports Zn2+ from the cytoplasm to the extracellular space. However, the functional transport properties regarding kinetics and driving forces of ZnT1 remain debatable. In this study, we established a cell-free proteoliposome assay system and demonstrated that ZnT1 transports Zn2+ with high affinity in pH-dependent and pH-independent manners. The Km and Vmax of pH-dependent Zn2+ transport were 0.40 ƒÊM and 15.13 nmol/min/mg protein, and those of pH-independent Zn2+ transport were 0.52 ƒÊM and 8.88 nmol/min/mg protein (low concentrations of Zn2+), 3.02 ƒÊM and 17.59 nmol/min/mg protein (high concentrations of Zn2+), respectively, suggesting biphasic kinetic components of Zn2+ transport. Even without pH gradient formation, ZnT1 exhibits potent Zn2+ transport activity. In pH dependency, Zn2+ transport activity was higher at an inside pH of 6.0 than at 6.5?7.5 for proteoliposomes, despite the same ƒ¢pH of 0.5?1.5. The Zn2+ transport activity decreased at an outside pH of 8.0, despite an increase in ƒ¢pH. Although previous studies have proposed that ZnT1-mediated Zn2+ transport activity is driven by a calcium (Ca2+) gradient and not by a pH gradient, Ca2+ does not enhance Zn2+ transport activity in the presence or absence of a pH gradient. These results strongly suggest that ZnT1 protein transports Zn2+ optimally at a specific pH and exports excess intracellular Zn2+ even without ƒ¢pH. en-copyright= kn-copyright= en-aut-name=YoshiokaYuma en-aut-sei=Yoshioka en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyajiTakaaki en-aut-sei=Miyaji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=zinc transporter 1 kn-keyword=zinc transporter 1 en-keyword=SLC30A1 kn-keyword=SLC30A1 en-keyword=zinc kn-keyword=zinc en-keyword=pH kn-keyword=pH en-keyword=proteoliposome kn-keyword=proteoliposome END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue= article-no= start-page=103265 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Peptide nanomicelles for NIR light-dependent siRNA delivery en-subtitle= kn-subtitle= en-abstract= kn-abstract=The peptide amphiphile PA8, derived from the GAVILRR peptide, was developed as a carrier for small interfering RNA (siRNA) delivery; however, its RNA interference (RNAi) efficacy was limited owing to predominant endocytotic uptake. In this study, the RNAi efficiency of PA8 nanomicelle/siRNA complexes was enhanced by modifying the nanomicelles with the photosensitizer DY750 and the tumor-homing peptide iRGD. The conjugation of DY750 to the nanomicelles facilitated endosomal escape of the nanomicelle/siRNA complexes, enabling the cytosolic release of siRNA. Additionally, the incorporation of iRGD improved RNAi delivery efficiency in the AsPC-1 pancreatic ductal adenocarcinoma cell line. PA8-DY750-iRGD nanomicelle complexes loaded with siRNA against polo-like kinase 1 (PLK1) achieved an 80% reduction in PLK1 mRNA levels in AsPC-1 cells and a moderate 28% knockdown in NCI-N87 gastric cancer cells. Notably, no RNAi effect was observed in noncancerous 1C3D3 pancreatic cells or HEK293T kidney cells, underscoring the selectivity of this system for AsPC-1 cells. These findings highlight the potential of PA8-DY750-iRGD nanomicelle complexes as a targeted therapeutic platform for specific cancers, particularly pancreatic cancer. en-copyright= kn-copyright= en-aut-name=HakimTaufik Fatwa Nur en-aut-sei=Hakim en-aut-mei=Taufik Fatwa Nur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitamatsuMizuki en-aut-sei=Kitamatsu en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujimotoShoumu en-aut-sei=Fujimoto en-aut-mei=Shoumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=4 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Peptide nanomicelles kn-keyword=Peptide nanomicelles en-keyword=siRNA kn-keyword=siRNA en-keyword=Near infrared light kn-keyword=Near infrared light en-keyword=Targeted delivery kn-keyword=Targeted delivery en-keyword=Photosensitizer kn-keyword=Photosensitizer END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=558 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of contact-active antibacterial properties of cetylpyridinium chloride?graphene oxide coatings on dental restorative and titanium surfaces: an in vitro study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Biofilm formation on dental restorative materials and implant surfaces plays a central role in the development of dental caries, periodontal disease, and peri-implantitis. Durable antimicrobial surface treatments that inhibit bacterial adhesion and biofilm formation remain a significant unmet need in restorative and implant dentistry. Therefore, this study aimed to develop a composite coating combining cetylpyridinium chloride and graphene oxide, and to evaluate its durable antibacterial surface modification under in vitro conditions.
Methods A composite coating consisting of cetylpyridinium chloride and graphene oxide was prepared and applied to composite resin and titanium surfaces. Antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis was evaluated using adenosine triphosphate assays and fluorescence-based live/dead staining. Coating retention after washing and air-drying was assessed by optical microscopy and Raman spectroscopy.
Results Cetylpyridinium chloride-graphene oxide-coated surfaces showed a significant reduction in bacterial viability compared with phosphate-buffered saline, ethanol, and cetylpyridinium chloride-only controls. Antibacterial effects were maintained after rinsing and air-drying on both composite resin and titanium surfaces. Raman spectroscopy confirmed the persistence of characteristic graphene oxide bands after washing, indicating stable retention of the coating on the material surfaces.
Conclusions Cetylpyridinium chloride?graphene oxide coatings demonstrate sustained surface-associated antibacterial activity against key cariogenic and periodontal pathogens and remain stably adhered to common dental restorative and implant materials after washing. These findings suggest that cetylpyridinium chloride?graphene oxide coatings may serve as a durable contact-active surface modification strategy to reduce biofilm formation associated with dental caries and peri-implantitis. en-copyright= kn-copyright= en-aut-name=OkuboKeisuke en-aut-sei=Okubo en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanoGen en-aut-sei=Kano en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KomodaMasato en-aut-sei=Komoda en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KamataHideyuki en-aut-sei=Kamata en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraShin en-aut-sei=Nakamura en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Periodontics and Endodontics, Field of Medical Development, 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=Research Institute for Interdisciplinary Science, 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 Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Wash-resistant antibacterial coating kn-keyword=Wash-resistant antibacterial coating en-keyword=Graphene oxide kn-keyword=Graphene oxide en-keyword=Cetylpyridinium chloride kn-keyword=Cetylpyridinium chloride en-keyword=Oral pathogenic bacteria kn-keyword=Oral pathogenic bacteria END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=2 article-no= start-page=831 end-page= 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=Porphyromonas gingivalis Vesicles Control Osteoclast?Macrophage Lineage Fate en-subtitle= kn-subtitle= en-abstract= kn-abstract=Porphyromonas gingivalis (Pg), a keystone pathogen of chronic periodontitis, releases outer membrane vesicles (OMVs) that act as nanoscale vehicles to disseminate virulence factors within periodontal tissues and systemically beyond the oral cavity. Although Pg-OMVs are increasingly recognized as critical mediators of host?pathogen interactions, their effects on the differentiation and function of monocyte?macrophage/osteoclast lineage cells remain unclear. Here, we examined the impact of Pg-OMVs on the differentiation of RAW264.7 monocyte/macrophage-like cells into osteoclasts (OC) and/or macrophages (Mƒ³) in the presence of receptor activator of nuclear factor-ƒÈB ligand (RANKL). OMVs were isolated from Pg W83 and applied to RANKL-primed RAW264.7 cells using three distinct stimulation schedules: (1) simultaneous treatment with Pg-OMVs and RANKL at Day 0; (2) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 1; and (3) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 3. In all schedules, cells were cultured for 7 days from the initial RANKL exposure. Remarkably, simultaneous exposure to Pg-OMVs and RANKL (Schedule 1) markedly suppressed osteoclastogenesis (OC-genesis) while promoting M1 macrophage polarization. In contrast, delayed Pg-OMV stimulation of RANKL-primed cells (Schedules 2 and 3) significantly enhanced OC-genesis while reducing M1 polarization. These schedule-dependent effects were consistent with altered expression of osteoclastogenic markers, including dc-stamp, oc-stamp, nfatc1, and acp5. Importantly, a monoclonal antibody against OC-STAMP counteracted the Pg-OMV-induced upregulation of OC-genesis in Schedules 2 and 3. Furthermore, levels of Pg-OMV phagocytosis were inversely correlated with osteoclast formation. Finally, co-stimulation with RANKL and Pg-OMVs (Schedule 1) enhanced macrophage migratory capacity, whereas delayed stimulation with Pg-OMVs (Schedules 2 and 3) did not. Collectively, these findings indicate that Pg-OMVs exert stage-specific effects on the OC/Mƒ³ lineage: stimulation at early stages of RANKL priming suppresses OC-genesis and promotes M1 polarization, whereas stimulation at later stages enhances OC-genesis without inducing M1 differentiation. Thus, Pg-OMVs may critically influence the fate of the OC/Mƒ³ unit in periodontal lesions, contributing to disease progression and tissue destruction. en-copyright= kn-copyright= en-aut-name=LeonElizabeth en-aut-sei=Leon en-aut-mei=Elizabeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraShin en-aut-sei=Nakamura en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShindoSatoru en-aut-sei=Shindo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PastoreMaria Rita en-aut-sei=Pastore en-aut-mei=Maria Rita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KumagaiTomoki en-aut-sei=Kumagai en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HeidariAlireza en-aut-sei=Heidari en-aut-mei=Alireza kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AbdolahiniaElaheh Dalir en-aut-sei=Abdolahinia en-aut-mei=Elaheh Dalir kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UedaTomoya en-aut-sei=Ueda en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MemidaTakumi en-aut-sei=Memida en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Duran-PinedoAna en-aut-sei=Duran-Pinedo en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Frias-LopezJorge en-aut-sei=Frias-Lopez en-aut-mei=Jorge kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HanXiaozhe en-aut-sei=Han en-aut-mei=Xiaozhe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ChenXin en-aut-sei=Chen en-aut-mei=Xin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HuangShengyuan en-aut-sei=Huang en-aut-mei=Shengyuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=CaoGuoqin en-aut-sei=Cao en-aut-mei=Guoqin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=RuizSunniva en-aut-sei=Ruiz en-aut-mei=Sunniva kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=PotempaJan en-aut-sei=Potempa en-aut-mei=Jan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawaiToshihisa en-aut-sei=Kawai en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=2 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=4 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=5 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=6 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=7 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=8 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=9 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=10 en-affil=Department of Oral Biology, College of Dentistry, University of Florida kn-affil= affil-num=11 en-affil=Department of Oral Biology, College of Dentistry, University of Florida kn-affil= affil-num=12 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=13 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=14 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=15 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=16 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=17 en-affil=Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville kn-affil= affil-num=18 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA kn-affil= en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=outer membrane vesicle kn-keyword=outer membrane vesicle en-keyword=periodontitis pathogenesis kn-keyword=periodontitis pathogenesis en-keyword=macrophage polarization kn-keyword=macrophage polarization en-keyword=osteoclastogenesis kn-keyword=osteoclastogenesis en-keyword=OC/Mƒ³ unit kn-keyword=OC/Mƒ³ unit END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=7 article-no= start-page=3143 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260330 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CXCR2-Dependent Infiltration of Tumor-Associated Neutrophils Is Linked to Enhanced CD8+ T Cell Effector Function and Reduced Lung Metastasis in 4T1 Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Triple-negative breast cancer (TNBC) is characterized by prominent neutrophil infiltration; however, its significance remains controversial. Here, we investigated the role of neutrophil chemoattractant receptors in TNBC progression and metastasis. In contrast to wild-type (WT), Fpr1?/?, and Fpr2?/? mice, neutrophils were almost completely absent in 4T1 tumors from Cxcr2?/? mice, indicating a dominant role for CXCR2 in the recruitment of tumor-associated neutrophils, leading us to use Cxcr2?/? mice for further studies. Primary tumor growth was comparable between WT and Cxcr2?/? mice, whereas lung metastasis was significantly increased in Cxcr2?/? mice, with reduced expression of inflammatory cytokines, chemokines and cytotoxic molecules, including granzyme B and perforin, in primary tumors and metastatic lungs of Cxcr2?/? mice. In vitro, WT, but not Cxcr2?/?, neutrophils enhanced CD8+ T cell activation, partly via ICAM-1, and directly induced tumor cell death, supporting their anti-tumor function. To assess clinical relevance, transcriptomic data were analyzed. High neutrophil infiltration combined with elevated CXCR2 expression, and to a lesser extent CXCR1 expression, was associated with improved prognosis in patients with basal-like BC that largely overlaps with TNBC. Collectively, these findings suggest that CXCR2-mediated neutrophil recruitment exerts protective, anti-tumor effects and may represent a new prognostic marker for TNBC patients. en-copyright= kn-copyright= en-aut-name=LiTiantian en-aut-sei=Li en-aut-mei=Tiantian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TianMiao en-aut-sei=Tian en-aut-mei=Miao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishidaGakushi en-aut-sei=Nishida en-aut-mei=Gakushi 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=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=neutrophils kn-keyword=neutrophils en-keyword=CD8+ T cells kn-keyword=CD8+ T cells en-keyword=chemokines kn-keyword=chemokines en-keyword=chemokine receptors kn-keyword=chemokine receptors en-keyword=tumor microenvironment kn-keyword=tumor microenvironment END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=4 article-no= start-page=760 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Role of Nitrate-Reducing Bacteria Isolated from Helicobacter pylori-Infected Individuals in Gastric Cancer Development en-subtitle= kn-subtitle= en-abstract= kn-abstract=Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric mucosa, with a global prevalence in humans of approximately 40%. It is likely the cause of 90% of gastric cancer (GC) cases and thus considered the most prominent driver of GC development. However, during gastric mucosal atrophy, other bacteria such as nitrate-reducing bacteria (NRB) also proliferate. In this study, we isolated NRB from patients with gastritis and GC to examine their effects on the epithelial cell cycle and production of various cytokines in monocytic cell lines. Bacterial counts (excluding H. pylori and NRB) increased with the progression of gastric mucosal atrophy and were significantly higher in patients with GC. Gastric epithelial cell lines were stimulated with isolated NRB, and the proportion of cells in each cell cycle was measured. Strains from patients with open-type gastritis progressed more rapidly through cell cycles than those from patients with GC. NRB isolated from gastric cancer had high nitrate-reducing activity. Thus, NRB may contribute to GC progression during H. pylori-induced carcinogenesis. Therefore, evaluating gastric atrophy and microbiota may be important for managing the risk of GC. en-copyright= kn-copyright= en-aut-name=KuwagiSerika en-aut-sei=Kuwagi en-aut-mei=Serika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KomatsubaraMarina en-aut-sei=Komatsubara en-aut-mei=Marina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=OkanoueShyoutarou en-aut-sei=Okanoue en-aut-mei=Shyoutarou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeAkari en-aut-sei=Watanabe en-aut-mei=Akari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YokotaKenji en-aut-sei=Yokota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Himeji Red Cross Hospital kn-affil= affil-num=7 en-affil=Department of Bacteriology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Health Care and Rehabilitation, Institute of Biomedical Sciences, Graduate School, Tokushima University kn-affil= affil-num=9 en-affil=Department of Bacteriology, Academic Field of Health Sciences, Okayama University kn-affil= en-keyword=Helicobacter pylori infection kn-keyword=Helicobacter pylori infection en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=nitrate-reducing bacteria kn-keyword=nitrate-reducing bacteria en-keyword=gastritis kn-keyword=gastritis END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=30309 end-page=30326 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Self-Adaptive Framework for Deploying Machine Learning Systems Without Ground-Truth Data at Runtime en-subtitle= kn-subtitle= en-abstract= kn-abstract=In recent years, the practical application of machine learning technology has rapidly progressed, accelerating its adoption across various fields. In this context, studies into the effective operation of machine learning systems in real-world environments have become essential. In actual operational settings, the distribution of input data often changes over time, leading to a significant decline in the predictive performance of models. Additionally, the lack of ground-truth data for test data during operation can sometimes make adaptation through retraining difficult. This study proposes a framework that autonomously adapts to changes in input data distribution, even in environments where ground-truth data for test data is unavailable during operation. This framework analyzes the distribution of input data and selects the appropriate predictive model based on the state of the distribution. To ensure optimal model selection, the framework employs two complementary approaches: 1) dynamically switching between multiple pre-trained models with different feature sets according to environmental changes and 2) building ensemble models based on the distribution of the test data. These approaches enable the framework to autonomously adapt to shifts in data distribution, even in operational settings where ground-truth data is unavailable. Evaluation experiments using both simulated and real-world data assessed the predictive performance of the proposed method through metrics such as R2, RMSE, and MAE. Compared to conventional single model predictions, the proposed method consistently demonstrated higher accuracy. These results indicate that the proposed approach effectively adapts to data distribution shifts in operational environments where ground-truth data is unavailable. en-copyright= kn-copyright= en-aut-name=FurukawaKento en-aut-sei=Furukawa en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaHiroyuki en-aut-sei=Nakagawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchiyaTatsuhiro en-aut-sei=Tsuchiya en-aut-mei=Tatsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Information Science and Technology, Osaka University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Information Science and Technology, Osaka University kn-affil= en-keyword=Self-adaptive systems kn-keyword=Self-adaptive systems en-keyword=frameworks kn-keyword=frameworks en-keyword=machine learning kn-keyword=machine learning 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, CaMK2ƒÁ, 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 ?M), 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 PP2Cƒ¿-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=75 cd-vols= no-issue=3-4 article-no= start-page=438 end-page=410 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A Study on Water Pollution by Persistent Organic PollutantsiPFOSEPFOAj: Focused on Duty of Care in Transactions. kn-title=PFOSEPFOA “™‚ÌŽc—¯«—L‹@‰˜õ•¨Ž¿‚É‚æ‚é…Ž¿‰˜õ‚ÉŠÖ‚·‚éˆêlŽ@ \ Žæˆøã‚Ì‹`–±‚ÌŽ‹“_‚©‚ç\ en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TsujiH. en-aut-sei=Tsuji en-aut-mei=H. kn-aut-name=’Ò”Ž–¾ kn-aut-sei=’Ò kn-aut-mei=”Ž–¾ aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=‰ªŽR‘åŠw–¼—_‹³Žö END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=139 end-page=152 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260328 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Practical Issues on Differences in Hours of Attendance as Seen in an Interview of Initial Appointment Child Care Teachers kn-title=‰”C•Ûˆç‹³—@‚ÌŒê‚è‚ÉŒ©‚鉀Ž™‚Ì݉€ŽžŠÔ‚̈Ⴂ‚É‚æ‚éŽÀ‘Hã‚̉ۑè en-subtitle= kn-subtitle= en-abstract=In this paper, we examined practical issues and responses through interviews with novice childcare teachers with a focus on the differences in the length of kindergarteners' attendance time, which characterizes certified childcare centers. As a result, it became obvious that childcare teachers were aware of eight challenges. In addition to the challenge with respect to the gdevelopment of childcare ensuring the continuity of playh described in the gGuidelines for Education and Childcare for Certified Childcare Centers,h furthermore, a new challenge regarding gunderstanding of kindergarteners in consideration of their various attendance time and lifestylesh not described in it was identified. Differences in attendance time due to certification classification inevitably lead to differences in time schedules, locations, and groups during certified childcare centers life. Therefore, in order to clarify what common experiences should be established in certified childcare centers life, what differences in experience should be utilized, and what kind of childcare should be practiced based on the goals set by childcare teachers, a future challenge is to collect and organize good practice examples that have been accumulated so far in certified nurseries and to clarify indicators. kn-abstract=@–{˜_‚Å‚ÍC—c•Û˜AŒgŒ^”F’肱‚Ç‚à‰€‚Ì“Á’¥‚Å‚ ‚鉀Ž™‚Ì݉€ŽžŠÔ‚̈Ⴂ‚ÉÅ“_‚ð“–‚ÄC‰”C•Ûˆç‹³—@‚Ö‚Ì–ÊÚ’²¸‚É‚æ‚èŽÀ‘Hã‚̉ۑè‚ƑΉž‚ɂ‚¢‚ÄŒŸ“¢‚µ‚½B‚»‚ÌŒ‹‰ÊC•Ûˆç‹³—@‚ª‚W‚‚̉ۑè‚ð”FŽ¯‚µ‚Ä‚¢‚邱‚Æ‚ª–¾‚ç‚©‚É‚È‚Á‚½B‚Ü‚½Cw—c•Û˜AŒgŒ^”F’肱‚Ç‚à‰€‹³ˆçE•Ûˆç—v—Ìx‚É‹Lq‚³‚ê‚Ä‚¢‚éu—V‚т̘A‘±«‚ð•Ûá‚·‚é•Ûˆç‚Ì“WŠJv‚ÉŠÖ‚·‚é‰Û‘è‚ɉÁ‚¦‚ÄC‹Lq‚³‚ê‚Ä‚¢‚È‚¢u‘½—l‚È݉€ŽžŠÔ‚ⶊˆŒ`‘Ô‚ðl—¶‚µ‚½‰€Ž™—‰ðv‚ÉŠÖ‚·‚éV‚½‚ȉۑ肪Œ©o‚³‚ꂽB”F’è‹æ•ª‚É‚æ‚é݉€ŽžŠÔ‚̈Ⴂ‚͉€¶Šˆ‚É‚¨‚¯‚鎞ŠÔ“IƒXƒPƒWƒ…[ƒ‹‚âêŠCW’c‚̈Ⴂ‚ð—]‹V‚È‚­‚³‚ê‚éB‚»‚Ì‚½‚ßC•Ûˆç‹³—@‚ªÝ’è‚·‚é‚Ë‚ç‚¢‚ÉŠî‚¢‚½‰€¶Šˆ‚ʼn½‚ð‹¤’ÊŒoŒ±‚Æ‚·‚ׂ«“à—e‚Æ‚µ‚Äݒ肵C‰½‚ðŒoŒ±·‚Æ‚µ‚ÄŠˆ‚©‚µC‚ǂ̂悤‚È•Ûˆç‚ðŽÀ‘H‚·‚é‚©–¾Šm‚É‚·‚ׂ­C‚±‚ê‚Ü‚Å”F’肱‚Ç‚à‰€‚ÅÏ‚Ýd‚Ë‚ç‚ê‚Ä‚«‚½DŽÀ‘H—á‚ðWÏE®—‚µCŽw•W‚𖾎¦‚·‚邱‚Æ‚ª¡Œã‚̉ۑè‚Å‚ ‚éB en-copyright= kn-copyright= en-aut-name=HASUIKazuya en-aut-sei=HASUI en-aut-mei=Kazuya kn-aut-name=˜@ˆä˜a–ç kn-aut-sei=˜@ˆä kn-aut-mei=˜a–ç aut-affil-num=1 ORCID= en-aut-name=KATAYAMAMika en-aut-sei=KATAYAMA en-aut-mei=Mika kn-aut-name=•ÐŽR”ü kn-aut-sei=•ÐŽR kn-aut-mei=”ü aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Health and WelfareC Kawasaki University of Medical Welfare kn-affil=ìèˆã—ÕŸŽƒ‘åŠwˆã—ÕŸŽƒŠw•” affil-num=2 en-affil=Faculty of Education, Graduate School of Science, Okayama University kn-affil=‰ªŽR‘åŠwŠwpŒ¤‹†‰@‹³ˆçŠwˆæ en-keyword=”F’肱‚Ç‚à‰€ (Certified Children Centers) kn-keyword=”F’肱‚Ç‚à‰€ (Certified Children Centers) en-keyword=݉€ŽžŠÔ‚̈Ⴂ (Differences in Hours of Attendance) kn-keyword=݉€ŽžŠÔ‚̈Ⴂ (Differences in Hours of Attendance) en-keyword=ŽÀ‘Hã‚̉ۑè (Issues in Childcare) kn-keyword=ŽÀ‘Hã‚̉ۑè (Issues in Childcare) en-keyword=‰”C•Ûˆç‹³—@ (Initial Appointment Child Care Teachers) kn-keyword=‰”C•Ûˆç‹³—@ (Initial Appointment Child Care Teachers) END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=123 end-page=137 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260328 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A Study on the Involvement of Community Wind Bands in the Community Development of Wind Band Activities; Can Community Wind Bands Serve as Key Supporters in Community Development of Club Activities? kn-title=‘tŠyŠˆ“®‚Ì’nˆæ“WŠJ‚É‚¨‚¯‚éŽs–¯‘tŠy’c‚ÌŠÖ‚í‚è‚ÉŠÖ‚·‚錤‹† \Žs–¯‘tŠy’c‚Í’nˆæ“WŠJ‚Ì’S‚¢Žè‚ɂȂ蓾‚é‚©\ en-subtitle= kn-subtitle= en-abstract=In the community development of wind band activities, the shortage of instructors and rehearsal spaces has become an urgent issue. This study investigates whether community wind bands can serve as key supporters of community development of childrenf s wind band activities progresses. Based on interviews with 20 community wind bands in Okayama Prefecture and text mining analysis, the study revealed differences in their awareness toward community development of club activities. More proactive bands tended to view providing musical instruction to children and engaging in joint activities positively. On the other hand, concerns about instructional skills, time constraints, and the burden of responsibility were identified as potential obstacles. Furthermore, the findings suggest that utilizing public school facilities could help address the issues of rehearsal space and financial constraints faced by community wind bands. However, disparities among municipalities were also found in the actual implementation of public school facility use systems. kn-abstract=@‘tŠyŠˆ“®‚Ì’nˆæ“WŠJiˆÈ‰ºA’nˆæ“WŠJj‚É‚¨‚¢‚ÄAŽw“±ŽÒ‚⊈“®êŠ‚Ì•s‘«‚Í‹i‹Ù‚̉ۑè‚Å‚ ‚éB–{Œ¤‹†‚ÍA’nˆæ“WŠJ‚ªi‚Þ’†‚ÅAŽs–¯‘tŠy’c‚ª’nˆæ‚ÌŽq‚Ç‚à’B‚Ì‘tŠyŠˆ“®‚ðŽx‚¦‚é’S‚¢Žè‚ƂȂ蓾‚é‚©‚𒲸EŒŸ“¢‚µ‚½B‰ªŽRŒ§“à‚ÌŽs–¯‘tŠy’c20 ’c‘Ì‚Ö‚Ì•·‚«Žæ‚è’²¸‚ƃeƒLƒXƒgƒ}ƒCƒjƒ“ƒO•ªÍ‚ÌŒ‹‰ÊA’nˆæ“WŠJ‚ւ̈ӎ¯‚É‚Í·‚ª‚Ý‚ç‚êAÏ‹É“I‚È’c‘Ì‚Å‚ÍŽq‚Ç‚à’B‚̉‰‘tŽw“±‚⇓¯‚Å‚ÌŠˆ“®‚ðm’è“I‚É‘¨‚¦‚éŒXŒü‚ªŠm”F‚³‚ꂽBˆê•û‚ÅAŽw“±‹Zp‚⎞ŠÔ“I§–ñAÓ”C•‰’S‚Ö‚Ì•sˆÀ‚ªá•Ç‚Æ‚È‚Á‚Ä‚¢‚é‰Â”\«‚ªŽ¦´‚³‚ꂽB‚Ü‚½AŽs–¯‘tŠy’c‚ª•ø‚¦‚銈“®êŠ‚âà­“I‚ȉۑè‚ɑ΂µ‚ÄŒö—§ŠwZŽ{Ý‚ÌŠˆ—p‚ª‚»‚Ì‰ðŒˆ‚ÉŠñ—^‚µ“¾‚é‰Â”\«‚ªŽ¦´‚³‚ꂽBˆê•û‚ÅAŒö—§ŠwZ‚ÌŽ{ÝŠJ•ú‚ɂ‚¢‚Ä‚ÍAŽÀۂ̧“x‰^—p‚É‚¨‚¢‚ÄŽ©Ž¡‘ÌŠÔ‚ÌŠi·‚ª‘¶Ý‚·‚邱‚Æ‚ª–¾‚ç‚©‚Æ‚È‚Á‚½B en-copyright= kn-copyright= en-aut-name=MAKINOKunihiko en-aut-sei=MAKINO en-aut-mei=Kunihiko kn-aut-name=ê –ì–M•F kn-aut-sei=ê –ì kn-aut-mei=–M•F aut-affil-num=1 ORCID= affil-num=1 en-affil=Center for Teacher Education and DevelopmentAOkayama University kn-affil=‰ªŽR‘åŠwŠwpŒ¤‹†‰@‹³ˆçŠwˆæ ‹³ˆç„i‹@\‹³Žt‹³ˆçŠJ”­ƒZƒ“ƒ^[ en-keyword=’nˆæ“WŠJ (community development of club activities) kn-keyword=’nˆæ“WŠJ (community development of club activities) en-keyword=Žs–¯‘tŠy’c (community wind band) kn-keyword=Žs–¯‘tŠy’c (community wind band) en-keyword=’nˆæƒNƒ‰ƒuŠˆ“® (regional club activities) kn-keyword=’nˆæƒNƒ‰ƒuŠˆ“® (regional club activities) en-keyword=ŠwZŽ{ÝŠJ•ú (community use of school facilities) kn-keyword=ŠwZŽ{ÝŠJ•ú (community use of school facilities) END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=45 end-page=59 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260328 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Physical Activity and Physical Fitness in the School Life of Elementary School Children kn-title=¬Šw¶‚ÌŠwZ¶Šˆ‚É‚¨‚¯‚ég‘ÌŠˆ“®—Ê‚Æ‘Ì—Í‚ÉŠÖ‚·‚錤‹† en-subtitle= kn-subtitle= en-abstract=@The purpose of this study was to objectively measure physical activity levels during different school settings among sixth-grade elementary school children using an accelerometer, and to examine their relationship with physical fitness. Participants were 85 children (41 boys, 44 girls). Step counts and time spent in different activity intensities were evaluated during recess, physical education (PE) classes, and the whole school day. Results showed that children with higher fitness levels tended to have greater step counts and more moderate-to-vigorous physical activity (MVPA) during recess. Significant differences were found in morning recess for boys and in lunch recess and PE classes for girls. The proportion of MVPA was 11.3% during recess and 15.7% during PE classes, which was lower than that reported in other countries and did not meet international recommendations. This study provides fundamental data on physical activity in elementary school settings and suggests the importance of enhancing opportunities for physical activity, parti cularly during recess and PE classes. kn-abstract=@–{Œ¤‹†‚Ì–Ú“I‚ÍC¬ŠwZ6”N¶‚ÌŠwZ¶Šˆ‚É‚¨‚¯‚銈“®ê–Ê•Ê‚Ìg‘ÌŠˆ“®—Ê‚ð‰Á‘¬“xŒv‚ð—p‚¢‚Ä‹qŠÏ“I‚É‘ª’肵C‚»‚Ì‘Ì—Í‚Æ‚ÌŠÖŒW‚ðŒŸ“¢‚·‚邱‚Æ‚Å‚ ‚éD‘ÎۂͬŠwZŽ™“¶85–¼(’jŽq41–¼C—Žq44–¼)‚Æ‚µC‹x‚ÝŽžŠÔC‘̈çŽö‹ÆCŠwZ¶Šˆ‘S‘Ì‚É‚¨‚¯‚é•à”‚Æ‹­“x•ÊŠˆ“®ŽžŠÔ‚ð•]‰¿‚µ‚½D‚»‚ÌŒ‹‰ÊC’j—‚Æ‚à‚É‘Ì—ÍãˆÊŒQ‚Í‹x‚ÝŽžŠÔ‚É‚¨‚¢‚Ä•à”‚ÆMVPA‚ª‘½‚¢ŒXŒü‚ªŽ¦‚³‚êC“Á‚É’jŽq‚Í’†‹x‚ÝC—Žq‚Í’‹‹x‚Ý‚¨‚æ‚ё̈çŽö‹Æ‚Å—LˆÓ·‚ª”F‚ß‚ç‚ꂽDŠeŠˆ“®ê–Ê‚ÌMVPA ‚ªè‚߂銄‡‚Í‹x‚ÝŽžŠÔ11.3“C‘̈çŽö‹Æ15.7“‚Å‚ ‚èC”ŠO‘‚Æ”äŠr‚µ‚Ä­‚È‚­C‘Û“I„§’l‚É‚à“Í‚©‚È‚©‚Á‚½D–{Œ¤‹†‚ÍC¬ŠwZ‚É‚¨‚¯‚ég‘ÌŠˆ“®—Ê‚ÌŠî‘bƒf[ƒ^‚ð’ñŽ¦‚·‚é‚Æ‚Æ‚à‚ÉCŠwZ¶ŠˆC“Á‚É‹x‚ÝŽžŠÔ‚â‘̈çŽö‹Æ‚É‚¨‚¯‚ég‘ÌŠˆ“®‹@‰ï‚Ì[ŽÀ‚ª•K—v‚Å‚ ‚邱‚Æ‚ðŽ¦´‚µ‚½D en-copyright= kn-copyright= en-aut-name=YASUNOBEJin en-aut-sei=YASUNOBE en-aut-mei=Jin kn-aut-name=ˆÀ‰„m kn-aut-sei=ˆÀ‰„ kn-aut-mei=m aut-affil-num=1 ORCID= en-aut-name=SASAYAMAKensaku en-aut-sei=SASAYAMA en-aut-mei=Kensaku kn-aut-name=ùŽRŒ’ì kn-aut-sei=ùŽR kn-aut-mei=Œ’ì aut-affil-num=2 ORCID= en-aut-name=ADACHIMinoru en-aut-sei=ADACHI en-aut-mei=Minoru kn-aut-name=‘«—§–« kn-aut-sei=‘«—§ kn-aut-mei=–« aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Education, Okayama University kn-affil=‰ªŽR‘åŠw‘åŠw‰@‹³ˆçŠwŒ¤‹†‰È affil-num=2 en-affil=Faculty of Education, Mie University kn-affil=ŽOd‘åŠw‹³ˆçŠw•” affil-num=3 en-affil=Faculty of Education, Okayama University kn-affil=‰ªŽR‘åŠwŠwpŒ¤‹†‰@‹³ˆçŠwˆæ en-keyword=‰Á‘¬“xŒv (accelerometer) kn-keyword=‰Á‘¬“xŒv (accelerometer) en-keyword=g‘ÌŠˆ“®—Ê (physical activity) kn-keyword=g‘ÌŠˆ“®—Ê (physical activity) en-keyword=‘Ì—Í (physical fitness) kn-keyword=‘Ì—Í (physical fitness) en-keyword=¬ŠwZŽ™“¶ (elementary school children) kn-keyword=¬ŠwZŽ™“¶ (elementary school children) END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1 end-page=13 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260328 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Preschool Teachersf Strategies and Practical Challenges in Supporting the School Enrollment of Foreign Children kn-title=ŠO‘l—cŽ™‚ÌAŠwŽx‰‡‚É‚¨‚¯‚é•ÛˆçŽm‚ÌH•v‚ÆŽÀ‘H“I‰Û‘è en-subtitle= kn-subtitle= en-abstract=This study aimed to clarify the specific practices and challenges faced by preschool teachers in supporting foreign children at the time of school enrollment. Semi-structured interviews were conducted with two preschool teachers who had experience in supporting foreign children, and qualitative analysis using SCAT was applied to organize the support provided to both children and their parents. The results revealed that, in terms of language support, teachers utilized visual aids and simplified Japanese, while in cultural support they sought to balance family culture with the culture of the preschool. Regarding developmental support, the importance of fostering non-cognitive skills and collaborating with medical institutions was highlighted. In parent support, participatory involvement and careful explanations were practiced; however, challenges remained in providing institutional information and establishing collaboration with local governments. Based on these findings, it is necessary to establish a regional collaborative system that can provide institutional support for families with multicultural backgrounds, standardize the provision of information, and build practical mechanisms to connect with Japanese language education resources, so that support does not rely solely on the individual efforts of preschool teachers. kn-abstract=@–{Œ¤‹†‚ÍCŠO‘l—cŽ™‚ªAŠwŠú‚É’¼–Ê‚·‚颓ï‚ɑΉž‚·‚邽‚ßC•ÛˆçŽm‚ªs‚Á‚Ä‚¢‚é‹ï‘Ì“I‚È•ÛˆçŽÀ‘H‚É‚¨‚¯‚éŽx‰‡‚ÌH•v‚Ɖۑè‚𖾂炩‚É‚·‚邱‚Æ‚ð–Ú“I‚Æ‚µ‚½BŠO‘l—cŽ™‚ÌŽx‰‡ŒoŒ±‚ð—L‚·‚é•ÛˆçŽm2 –¼‚É”¼\‘¢‰»ƒCƒ“ƒ^ƒrƒ…[‚ðs‚¢CSCAT ‚ð—p‚¢‚½Ž¿“I•ªÍ‚É‚æ‚èC—cŽ™‚¨‚æ‚Ñ•ÛŒìŽÒ‚Ö‚ÌŽx‰‡“à—e‚ð®—‚µ‚½B‚»‚ÌŒ‹‰ÊCŒ¾Œê–Ê‚Å‚ÍŽ‹Šo“IŽx‰‡‚â‚₳‚µ‚¢“ú–{Œê‚ðŠˆ—p‚µC•¶‰»–ʂł͉ƒ땶‰»‚Æ“ú–{‚̉€•¶‰»‚Ì’²®‚ªs‚í‚ê‚Ä‚¢‚½B”­’BŽx‰‡‚É‚¨‚¢‚Ä‚ÍC”ñ”F’m“IƒXƒLƒ‹‚̈笂âˆã—Ë@ŠÖ‚Ƃ̘AŒg‚Ì•K—v«‚ªŽw“E‚³‚ꂽB•ÛŒìŽÒŽx‰‡‚Å‚ÍCŽQ‰ÁŒ^‚ÌŠÖ‚í‚è‚â’š”J‚Èà–¾‚ªŽÀ‘H‚³‚ê‚Ä‚¢‚½‚ªC§“xî•ñ‚Ì’ñ‹Ÿ‚âs­‚Ƃ̘AŒg‚ɂ͉ۑ肪Žc‚³‚ꂽB‚±‚ê‚ç‚ÌŒ‹‰Ê‚𓥂܂¦C¡Œã‚Í•ÛˆçŽm‚̌•ʓI“w—͂Ɉˑ¶‚µ‚È‚¢‚½‚ß‚É‚àC‘½•¶‰»”wŒi‚ð‚à‚‰ƒë‚Ö‚ÌŽx‰‡‚ð§“x“I‚ÉŽx‚¦‚é’nˆæ˜AŒg‘̧‚Ì®”õ‚âCî•ñ’ñ‹Ÿ‚Ì•W€‰»C“ú–{Œê‹³ˆçŽ‘Œ¹‚Æ‚ÌÚ‘±‚ð}‚éŽÀ‘H“IŽd‘g‚Ý‚Ì\’z‚ª‹‚ß‚ç‚ê‚éB en-copyright= kn-copyright= en-aut-name=CHENYiwen en-aut-sei=CHEN en-aut-mei=Yiwen kn-aut-name=’ˆ˕¶ kn-aut-sei=’ kn-aut-mei=ˆË•¶ aut-affil-num=1 ORCID= en-aut-name=YANAGISAWAKazuki en-aut-sei=YANAGISAWA en-aut-mei=Kazuki kn-aut-name=–öàV‰ÀŒŽ kn-aut-sei=–öàV kn-aut-mei=‰ÀŒŽ aut-affil-num=2 ORCID= en-aut-name=REN Xinyu en-aut-sei=REN en-aut-mei= Xinyu kn-aut-name=”Cc˜° kn-aut-sei=”C kn-aut-mei=c˜° aut-affil-num=3 ORCID= en-aut-name=YOSHITOSHIMunehisa en-aut-sei=YOSHITOSHI en-aut-mei=Munehisa kn-aut-name=‹g—˜@‹v kn-aut-sei=‹g—˜ kn-aut-mei=@‹v aut-affil-num=4 ORCID= affil-num=1 en-affil=The Joint Graduate School (Ph.D. Program) in Science of School Education, Hyogo University of Teacher, Hyogo University of Teacher Education kn-affil=•ºŒÉ‹³ˆç‘åŠw‘åŠw‰@˜A‡ŠwZ‹³ˆçŠwŒ¤‹†‰È”ŽŽm‰Û’ö affil-num=2 en-affil=Graduate School of Education, Okayama University kn-affil=‰ªŽR‘åŠw‘åŠw‰@‹³ˆçŠwŒ¤‹†‰È affil-num=3 en-affil=Graduate School of Education, Okayama University kn-affil=‰ªŽR‘åŠw‘åŠw‰@‹³ˆçŠwŒ¤‹†‰È affil-num=4 en-affil=Faculty of Education, Okayama University kn-affil=‰ªŽR‘åŠwŠwpŒ¤‹†‰@‹³ˆçŠwˆæ en-keyword=ŠO‘l—cŽ™ (foreign preschool children) kn-keyword=ŠO‘l—cŽ™ (foreign preschool children) en-keyword=AŠw (school enrollment) kn-keyword=AŠw (school enrollment) en-keyword=•ÛˆçŽm (preschool teachers) kn-keyword=•ÛˆçŽm (preschool teachers) 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=2026 dt-pub=20260325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinicopathological and transcriptomic profiles of 101 patients with diffuse large B-cell lymphoma/high-grade B-cell lymphoma with double-hit MYC and BCL2 or BCL6 and triple hit en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBCL) with MYC and BCL2 rearrangements (double-hit lymphoma with BCL2, DHL-BCL2) is a mature aggressive B-cell lymphoma that also includes concurrent triple hit with BCL6 translocation (TH). DHL with MYC and BCL6 (DH-BCL6) can also occur. The differences among these three DLBCL/HGBCL subtypes have not yet been definitively determined.
Methods and Results: This study characterized the clinicopathological features and transcriptomic profiles of a series of 101 cases of DLBCL/HGBCL that were subclassified according to MYC, BCL2 and BCL6 FISH data, including cell-of-origin (COO)-like, molecular high-grade (MHG)-like and double-hit/dark-zone (DHIT/DZsig)-like signatures. DLBCL/HGBCL-DH-BCL2 was characterized by higher HGBCL morphology, CD10 positivity, GCB Hans's, GCB COO and MHG molecular subtype. DLBCL/HGBCL-TH had higher LDH levels and worse overall survival. DLBCL/HGBCL-DH-BCL6 had higher MUM1 expression, non-GCB Hans', ABC/Unclassified COO, non-MHG and low DHIT/DZ signatures. Transcriptomic analysis showed that DLBCL/HGBCL-DH-BCL2 and DLBCL/HGBCL-TH were close but separated from DLBCL/HGBCL-DH-BCL6. Gene set enrichment analysis (GSEA) revealed different levels of enrichment between the subtypes.
Conclusions: DLBCL/HGBCL-DH-BCL6 differs from the DLBCL/HGBCL-DH-BCL2, and the DLBCL/HGBCL-TH is associated with the worst survival. Analysis of all three genes of MYC, BCL2 and BCL6 is recommended in the context of DLBCL/HGBCL diagnosis. en-copyright= kn-copyright= en-aut-name=MiyaokaMasashi en-aut-sei=Miyaoka en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CarrerasJoaquim en-aut-sei=Carreras en-aut-mei=Joaquim kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikutiYara Yukie en-aut-sei=Kikuti en-aut-mei=Yara Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkomaHaruka en-aut-sei=Ikoma en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagaseShunsuke en-aut-sei=Nagase en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoAtsushi en-aut-sei=Ito en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OritaMakoto en-aut-sei=Orita en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawadaHiroshi en-aut-sei=Kawada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakaiRika en-aut-sei=Sakai en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsukasakiKunihiro en-aut-sei=Tsukasaki en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KameokaYoshihiro en-aut-sei=Kameoka en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YoshidaMasahiro en-aut-sei=Yoshida en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SatouAkira en-aut-sei=Satou en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KatoSeiichi en-aut-sei=Kato en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OishiNaoki en-aut-sei=Oishi en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SaitoAkio en-aut-sei=Saito en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SadahiraKen en-aut-sei=Sadahira en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MasugiYohei en-aut-sei=Masugi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=NakamuraNaoya en-aut-sei=Nakamura en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=2 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=3 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=4 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=5 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=6 en-affil=Department of Pathology, School of Medicine Tokai University Isehara Japan kn-affil= affil-num=7 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=8 en-affil=Department of Hematology, School of Medicine, Tokai University kn-affil= affil-num=9 en-affil=Department of Medical Oncology, Kanagawa Cancer Center kn-affil= affil-num=10 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=11 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=12 en-affil=Department of Hematology, International Medical Center, Saitama Medical University kn-affil= affil-num=13 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=14 en-affil=Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Hematology, Osaka City General Hospital kn-affil= affil-num=16 en-affil=Department of Surgical Pathology, Aichi Medical University Hospital kn-affil= affil-num=17 en-affil=Center for Clinical Pathology, Fujita Health University Hospital kn-affil= affil-num=18 en-affil=Department of Pathology, University of Yamanashi kn-affil= affil-num=19 en-affil=Department of Hematology, NHO Shibukawa Medical Center kn-affil= affil-num=20 en-affil=Division of Hematology, Kawasaki Municipal Kawasaki Hospital kn-affil= affil-num=21 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= affil-num=22 en-affil=Department of Pathology, School of Medicine, Tokai University kn-affil= en-keyword=BCL2 kn-keyword=BCL2 en-keyword=BCL6 kn-keyword=BCL6 en-keyword=high-grade B-cell lymphoma kn-keyword=high-grade B-cell lymphoma en-keyword=molecular profile kn-keyword=molecular profile en-keyword=MYC kn-keyword=MYC en-keyword=rearrangements kn-keyword=rearrangements END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=84 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A real-world comparison of nivolumab plus cabozantinib and pembrolizumab plus lenvatinib focusing on safety outcomes in metastatic renal cell carcinoma: results from the JK-FOOT consortium en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Immune checkpoint inhibitor (ICI)-based combination therapy is a standard first-line treatment for metastatic renal cell carcinoma (mRCC), with combinations such as nivolumab plus cabozantinib (Nivo?+?Cabo) and pembrolizumab plus lenvatinib (Pem?+?Len) demonstrating favorable oncologic outcomes. However, no direct comparisons between these two regimens have been conducted. This study aimed to compare the safety and oncologic outcomes of Nivo?+?Cabo and Pem?+?Len in patients with mRCC.
Methods This retrospective study included 185 patients with mRCC treated with Nivo?+?Cabo (n?=?81) or Pem?+?Len (n?=?104) between January 2018 and June 2025 across multiple institutions. The primary outcome was a comparison of treatment-related adverse events (TrAEs). Oncologic outcomes, including objective response rate (ORR), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared using one-to-one propensity score matching.
Results Any-grade TrAEs occurred in 90% of patients in the Nivo?+?Cabo group and 92% in the Pem?+?Len group (p?=?0.6). Severe TrAEs (grade???3) were more frequent in the Pem?+?Len group (44%) than in the Nivo?+?Cabo group (30%, p?=?0.048). Tyrosine kinase inhibitor dose reduction and treatment discontinuation rates were similar between groups. In the matched cohort (Nivo?+?Cabo: n?=?74; Pem?+?Len: n?=?74), ORRs were comparable (66% vs. 71%, p?=?0.6). With a median follow-up of 17 months, no significant differences were observed in PFS (p?=?0.4), CSS (p?=?0.9), or OS (p?=?0.5).
Conclusions Nivo?+?Cabo and Pem?+?Len demonstrated similar oncologic efficacy as first-line treatments for mRCC. However, Pem?+?Len was associated with more severe TrAEs. Careful toxicity management and shared decision-making are essential when selecting ICI-based combinations. en-copyright= kn-copyright= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro 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=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujinoTakuya en-aut-sei=Tsujino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyodaShingo en-aut-sei=Toyoda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NukayaTakuhisa en-aut-sei=Nukaya en-aut-mei=Takuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorinakaHirofumi en-aut-sei=Morinaka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TamuraKeita en-aut-sei=Tamura en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UrabeFumihiko en-aut-sei=Urabe en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MurakamiMasaya en-aut-sei=Murakami en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujitaKazutoshi en-aut-sei=Fujita en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AzumaHaruhito en-aut-sei=Azuma en-aut-mei=Haruhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 ORCID= en-aut-name=InamotoTeruo en-aut-sei=Inamoto en-aut-mei=Teruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KomuraKazumasa en-aut-sei=Komura en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KimuraTakahiro en-aut-sei=Kimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=5 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=6 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Urology, Faculty of Medicine, Kindai University kn-affil= affil-num=8 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Urology, Hamamatsu Medical University kn-affil= affil-num=11 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=14 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=16 en-affil=Department of Urology, Faculty of Medicine, Kindai University kn-affil= affil-num=17 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=18 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Urology, Hamamatsu Medical University kn-affil= affil-num=20 en-affil=Department of Urology, Kawasaki Medical School kn-affil= affil-num=21 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= en-keyword=Metastatic renal cell carcinoma kn-keyword=Metastatic renal cell carcinoma en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor en-keyword=Pembrolizumab kn-keyword=Pembrolizumab en-keyword=Lenvatinib kn-keyword=Lenvatinib en-keyword=Nivolumab kn-keyword=Nivolumab en-keyword=Cabozantinib kn-keyword=Cabozantinib END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=3 article-no= start-page=55 end-page=59 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260315 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Low Temperature Formation of Dense Yttria-Stabilized Zirconia Layer Using Hot Isostatic Pressing kn-title=”MŠÔÃ…ˆ³‰Áˆ³–@‚ð—p‚¢‚½ƒCƒbƒgƒŠƒAˆÀ’艻ƒWƒ‹ƒRƒjƒAãk–§‘w‚̒ቷŒ`¬ en-subtitle= kn-subtitle= en-abstract= kn-abstract=The sintering conditions using hot isostatic press (HIP) of yttria-stabilized zirconia (YSZ) were investigated to obtain a dense YSZ layer at low sintering temperature such as 1000‹C for an electrolyte of metal-supported solid oxide fuel cell. It was found that a dense YSZ pellet with relative density of 93% could be obtained under a sintering condition of 1000‹C-10 hours with HIP in 195 MPa. On the other hand, in X-ray diffraction analysis of the dense YSZ pellet, peaks of the monoclinic phase were slightly detected in addition to peaks of the cubic phase. From energy dispersive X-ray spectroscopy analysis, a small amount of boron was detected in the dense YSZ pellet. It is considered that the YSZ crystalline phase transformation of cubic to monoclinic phase was occurred by the boron diffusion from the diffusion barrier coating of metal foil capsule used for the HIP. en-copyright= kn-copyright= en-aut-name=MANABEKyohei en-aut-sei=MANABE en-aut-mei=Kyohei kn-aut-name=^“ç‹•½ kn-aut-sei=^“ç kn-aut-mei=‹•½ aut-affil-num=1 ORCID= en-aut-name=ECHIGOMitsuaki en-aut-sei=ECHIGO en-aut-mei=Mitsuaki kn-aut-name=‰zŒã–žH kn-aut-sei=‰zŒã kn-aut-mei=–žH aut-affil-num=2 ORCID= en-aut-name=KISHIMOTOAkira en-aut-sei=KISHIMOTO en-aut-mei=Akira kn-aut-name=ŠÝ–{º kn-aut-sei=ŠÝ–{ kn-aut-mei=º aut-affil-num=3 ORCID= affil-num=1 en-affil=Osaka Gas Co. Ltd. kn-affil=‘åãƒKƒXiŠ”j affil-num=2 en-affil=Osaka Gas Co. Ltd. kn-affil=‘åãƒKƒXiŠ”j affil-num=3 en-affil=Institute of Academic and Research, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil=‰ªŽR‘åŠwŠwpŒ¤‹†‰@ŠÂ‹«¶–½Ž©‘R‰ÈŠwŠwˆæ en-keyword=dense yttria-stabilized zirconia kn-keyword=dense yttria-stabilized zirconia en-keyword=hot isostatic press kn-keyword=hot isostatic press en-keyword=low sintering temperature kn-keyword=low sintering temperature en-keyword=electrolyte kn-keyword=electrolyte en-keyword=metal-supported solid oxide fuel cell kn-keyword=metal-supported solid oxide fuel cell END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=35 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=A case of tubulointerstitial nephritis with infiltration of neutrophils and interleukin-17-positive cells associated with Beh?etfs disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Beh?etfs disease (BD) is a non-infectious inflammatory condition characterized by neutrophilic infiltration. In addition to primary symptoms, including oral and genital ulcers, ocular involvement, and skin lesions, BD can also affect various organs. However, renal involvement, particularly in tubulointerstitial nephritis, has rarely been described. Herein, a rare case of acute tubulointerstitial nephritis in a patient clinically diagnosed with BD is reported. The renal lesion presented with other symptoms of BD and fever, and was considered to be BD-related due to the presence of neutrophilic infiltration and its responsiveness to BD-directed therapy. Alterations in T-helper (Th) 1, Th2, and Th17 cytokine profiles are associated with BD activity. Interleukin (IL)-17 plays a central role in neutrophil activation, and recent studies have demonstrated a strong correlation between IL-17A levels and BD activity. In the present case, elevated serum IL-17A levels and infiltration of IL-17A-positive cells into the renal tissue reflected an active phase of BD and a BD-associated renal lesion. en-copyright= kn-copyright= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KubotaNatsuki en-aut-sei=Kubota en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Tubulointerstitial nephritis kn-keyword=Tubulointerstitial nephritis en-keyword=Beh?etfs disease kn-keyword=Beh?etfs disease en-keyword=Neutrophils kn-keyword=Neutrophils en-keyword=Interleukin-17 kn-keyword=Interleukin-17 en-keyword=T-helper (Th) 1/Th2/Th17 cytokines kn-keyword=T-helper (Th) 1/Th2/Th17 cytokines END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=3 article-no= start-page=e202500639 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PPy]Coated Wire Actuators for the Micromechanostimulation of Cells: Fabrication and Characterization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cellular mechanotransduction signals play a crucial role in physiological and pathological conditions, including skeletal disorders. Although various systems exist to mechanically stimulate cultured cells, most are constrained by incubator incompatibility, limited physiological relevance, nonuniform stimulation, or complexity. The objective of this article is to develop and validate a compact, incubator-compatible tool capable of delivering localized and physiologically relevant mechanical stimulation to small cell populations. Here, we introduce a polypyrrole-based wire-shaped microactuator designed to induce localized mechanical stress to adjacent cells. These wire-shaped microactuators are biocompatible, easy-to-use, and compact for use within standard in vitro cell culture systems. Using a noncontact optical method, we characterize the actuation of polypyrrole-coated wires in an aqueous NaDBS electrolyte, showing radial expansion of 1.5?8??m depending on the deposited polypyrrole film thickness, comparable to cellular dimensions. Next, the actuation is confirmed to be robust and stable to use in cell culture media at physiological temperature. To evaluate biological relevance, osteoblastic KUSA-A1 cells are mechanically stimulated inside the incubator and transcriptomic changes are assessed. Mechanical stimulation resulted in upregulation of genes previously associated with mechanotransduction, including Fos and Fosb. Additionally, several uncharacterized long noncoding RNAs are differentially expressed, suggesting potential novel players in the mechanotransduction pathway. en-copyright= kn-copyright= en-aut-name=Ortega]SantosAmaia B. en-aut-sei=Ortega]Santos en-aut-mei=Amaia B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayanoSatoru en-aut-sei=Hayano en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Mart?nezJose G. en-aut-sei=Mart?nez en-aut-mei=Jose G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JagerEdwin W. H. en-aut-sei=Jager en-aut-mei=Edwin W. H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Link?ping University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Advanced Research Center for Oral and Craniofacial Sciences Dental School, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Link?ping University kn-affil= affil-num=5 en-affil=Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Sensor and Actuator Systems, Department of Physics Chemistry and Biology (IFM), Link?ping University kn-affil= en-keyword=conducting polymers kn-keyword=conducting polymers en-keyword=mechanotransduction kn-keyword=mechanotransduction en-keyword=osteoblasts kn-keyword=osteoblasts en-keyword=polypyrrole kn-keyword=polypyrrole en-keyword=RNA sequencing kn-keyword=RNA sequencing en-keyword=soft-microactuators kn-keyword=soft-microactuators END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=133 end-page=142 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251016 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Study on Zeek IDS Effectiveness for Cybersecurity in Agricultural IoT Networks en-subtitle= kn-subtitle= en-abstract= kn-abstract=As agriculture moves toward Agriculture 4.0, which uses Internet of Things (IoT) devices to collect data in real time and monitor things from a distance, these networks are becoming increasingly vulnerable to cyberattacks. A common method used to protect against these kinds of threats is the use of intrusion detection systems (IDS). However, the agricultural environment is often changing and has limited resources, which makes cybersecurity challenging. Several available IDS tools are not designed to work properly in places with few resources, intermittent access, and unpredictable network conditions. This paper investigates the performance of Zeek, an open-source IDS, in identifying potential threats in agricultural IoT networks. We performed both offline and real-time experiments: offline analysis used pcap files from the Stratosphere Laboratory dataset, and real-time evaluation involved simulated live attack scenarios, focusing on unauthorized access attempts and distributed denial-of-service (DDoS) attacks. Zeek's performance was assessed based on CPU and memory utilization, as well as quality of service (QoS) metrics. From the experimental results, we found that Zeek was quite effective in protecting agricultural IoT networks against typical threats. Memory usage remained stable around 5% during offline analysis and under 20% during active attacks. However, CPU usage was more volatile, peaking at 120% during DDoS events. In terms of QoS, the system maintained a good throughput (1,375 kbits/s) with minimal packet loss (0.000186%). Among the attack types that we tested, brute force attacks, which represent attempts at unauthorized access, had the strongest effect on network performance, increasing delay to 2.159 ms and jitter to 0.793 ms. It seems clear that a heavier traffic load during such attacks can interfere with QoS. On the basis of our observation, we recommend practical deployment strategies for agricultural IoT systems that take these limitations into consideration, aiming to keep networks both secure and efficient under pressure. en-copyright= kn-copyright= en-aut-name=HudaSamsul en-aut-sei=Huda en-aut-mei=Samsul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MusthafaMuhammad Bisri en-aut-sei=Musthafa en-aut-mei=Muhammad Bisri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShamimS. M. en-aut-sei=Shamim en-aut-mei=S. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NogamiYasuyuki en-aut-sei=Nogami en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Interdisciplinary Education and Research Field, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=agricultural IoT kn-keyword=agricultural IoT en-keyword=Zeek IDS kn-keyword=Zeek IDS en-keyword=intrusion detection systems kn-keyword=intrusion detection systems en-keyword=open-source security tools kn-keyword=open-source security tools en-keyword=Agriculture 4.0 kn-keyword=Agriculture 4.0 en-keyword=cybersecurity kn-keyword=cybersecurity en-keyword=Raspberry Pi kn-keyword=Raspberry Pi END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue= article-no= start-page=59 end-page=68 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=Practical BIZEN Device Design Course Activity Report in Fiscal 2025 kn-title=2025 ”N“xŽŸ¢‘ãˆã—Ë@ŠíŠJ”­lވ笃vƒƒOƒ‰ƒ€ BIZEN ƒfƒoƒCƒXƒfƒUƒCƒ“ƒR[ƒX‚ÌŽæ‚è‘g‚Ý en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TSUZUKITsuneaki en-aut-sei=TSUZUKI en-aut-mei=Tsuneaki kn-aut-name=“s’zí–¾ kn-aut-sei=“s’z kn-aut-mei=í–¾ aut-affil-num=1 ORCID= en-aut-name=UCHIDADaisuke en-aut-sei=UCHIDA en-aut-mei=Daisuke kn-aut-name=“à“c‘å•ã kn-aut-sei=“à“c kn-aut-mei=‘å•ã aut-affil-num=2 ORCID= en-aut-name=KISHIMOTOToshio en-aut-sei=KISHIMOTO en-aut-mei=Toshio kn-aut-name=ŠÝ–{r•v kn-aut-sei=ŠÝ–{ kn-aut-mei=r•v aut-affil-num=3 ORCID= en-aut-name=SENGOKUYoshinari en-aut-sei=SENGOKU en-aut-mei=Yoshinari kn-aut-name=åΊì–ç kn-aut-sei=åÎ kn-aut-mei=Šì–ç aut-affil-num=4 ORCID= en-aut-name=KORENAGAToshio en-aut-sei=KORENAGA en-aut-mei=Toshio kn-aut-name=ˆÉ‰ir—Y kn-aut-sei=ˆÉ‰i kn-aut-mei=r—Y aut-affil-num=5 ORCID= en-aut-name=HITOBEYu en-aut-sei=HITOBE en-aut-mei=Yu kn-aut-name=l•”—F kn-aut-sei=l•” kn-aut-mei=—F aut-affil-num=6 ORCID= en-aut-name=YOSHIBAYasuyuki en-aut-sei=YOSHIBA en-aut-mei=Yasuyuki kn-aut-name=‹g—t‹±s kn-aut-sei=‹g—t kn-aut-mei=‹±s aut-affil-num=7 ORCID= en-aut-name=SAKURAIJun en-aut-sei=SAKURAI en-aut-mei=Jun kn-aut-name=ŸNˆä~ kn-aut-sei=ŸNˆä kn-aut-mei=~ aut-affil-num=8 ORCID= affil-num=1 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil=‰ªŽR‘åŠw•a‰@ Vˆã—ÃŒ¤‹†ŠJ”­ƒZƒ“ƒ^[ affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil=‰ªŽR‘åŠw•a‰@ Vˆã—ÃŒ¤‹†ŠJ”­ƒZƒ“ƒ^[ affil-num=3 en-affil=Organization for Research and Innovation Strategy, Okayama University kn-affil=‰ªŽR‘åŠw Œ¤‹†EƒCƒmƒx[ƒVƒ‡ƒ“‹¤‘n‹@\ affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil=‰ªŽR‘åŠw•a‰@ Vˆã—ÃŒ¤‹†ŠJ”­ƒZƒ“ƒ^[ affil-num=5 en-affil=Organization for Research and Innovation Strategy, Okayama University kn-affil=‰ªŽR‘åŠw Œ¤‹†EƒCƒmƒx[ƒVƒ‡ƒ“‹¤‘n‹@\ affil-num=6 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil=‰ªŽR‘åŠw•a‰@ Vˆã—ÃŒ¤‹†ŠJ”­ƒZƒ“ƒ^[ affil-num=7 en-affil=Academic Field of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=‰ªŽR‘åŠwŠwpŒ¤‹†‰@ƒwƒ‹ƒXƒVƒXƒeƒ€“‡‰ÈŠwŠwˆæ affil-num=8 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil=‰ªŽR‘åŠw•a‰@ Vˆã—ÃŒ¤‹†ŠJ”­ƒZƒ“ƒ^[ END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue= article-no= start-page=17 end-page=25 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=Patient Participation in Shared Decision-Making: A Consideration of Aspects and Challenges kn-title=Shared Decision Making ‚É‚¨‚¯‚銳ŽÒŽQ‰Á‚Ì”‘Š‚Ɖۑè‚ÌlŽ@ en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper traces the historical development of decision-making models in healthcare while exploring the meaning and practical significance of gpatient participationh within the shared decision-making (SDM) framework. SDM is a recommended approach to clinical decision-making that emphasizes mutual information sharing and deliberation between physicians and patients. Traditional models often assume that patients can clearly articulate their values, preferences, and treatment goals. However, in actual clinical settings, particularly in cases of serious illness or life-threatening situations, patients frequently face emotional distress and psychological burdens, which can hinder their active participation in decision-making and the expression of their preferences. Based on SDM theory and practice reports, this study argues that SDM should not be viewed merely as a process that promotes patient choice. Even when patients choose not to actively participate and ultimately delegate decisions to healthcare providers or family members, such a choice can represent autonomous decision-making if it arises through meaningful communication and mutual understanding. This perspective calls for a more comprehensive and flexible interpretation of patient participation in SDM practice. en-copyright= kn-copyright= en-aut-name=YOSHIDAMiho en-aut-sei=YOSHIDA en-aut-mei=Miho kn-aut-name=‹g“c”ü•ä kn-aut-sei=‹g“c kn-aut-mei=”ü•ä aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems Okayama University kn-affil=‘—§‘åŠw–@l‰ªŽR‘åŠwŠwpŒ¤‹†‰@ƒwƒ‹ƒXƒVƒXƒeƒ€“‡‰ÈŠwŒ¤‹†Šwˆæ en-keyword=Shared Decision-Making kn-keyword=Shared Decision-Making en-keyword=Patient Participation kn-keyword=Patient Participation en-keyword=Physician?Patient Relationship kn-keyword=Physician?Patient Relationship END start-ver=1.4 cd-journal=joma no-vol=2025 cd-vols= no-issue= article-no= start-page=9884345 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparing the Activity of Peripheral Blood Mononuclear Cells Frozen Under Electromagnetic Field Freezing and Standard Slow-Freezing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Peripheral blood mononuclear cells (PBMCs) are cells obtained from the blood that are used not only in clinical tests but also in various research applications. The slow-freezing (SLF) method, currently the standard for PBMC cryopreservation, involves extended storage at ?80‹C before transfer to liquid nitrogen. Delays in this transfer, such as overnight or weekend holds, risk a gradual decline in cell viability. Additionally, variability in freezing duration can lead to inconsistent cell quality, emphasizing the need for an alternative freezing method that allows for more timely transfer to liquid nitrogen. This study is aimed at clarifying whether the method of using a freezer with an applied electromagnetic field (EMF) is superior to the currently used standard SLF method for PBMC cryopreservation. A comparison of the number of viable cells, cell viability, and cell activity showed that the EMF method was equivalent to the SLF method. However, the shortest time required for freezing was significantly shorter with the EMF method than the SLF method (0.25 vs. 3?h), allowing for earlier transfer of PBMC to liquid nitrogen. This demonstrates that the EMF method offers an advantage in operational efficiency, particularly for facilities that routinely process and store PBMCs, such as biobanks and other storage-focused departments. en-copyright= kn-copyright= en-aut-name=MatsubaraTakehiro en-aut-sei=Matsubara en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiMina en-aut-sei=Takagi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UwaboTakahiro en-aut-sei=Uwabo en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=MoritaMizuki en-aut-sei=Morita en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Okayama University Hospital Biobank kn-affil= affil-num=2 en-affil=Faculty of Health Sciences, Okayama University Medical School kn-affil= affil-num=3 en-affil=Department of Biorepository Research and Networking, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Okayama University Hospital Biobank kn-affil= affil-num=6 en-affil=Okayama University Hospital Biobank kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=8840 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260317 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tribolium castaneum with longer duration of tonic immobility have more variations corresponding to the human Parkinsonfs disease genomic region en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinsonfs disease (PD) is a common neurodegenerative syndrome characterized by the loss of dopaminergic neurons and is also a progressive neurodegenerative disorder that is characterized by dopamine deficiency. We established strains artificially selected for longer and shorter durations of tonic immobility, an antipredator behavior that has received much attention recently, in the red flour beetle, Tribolium castaneum, a model insect species for molecular analyses different from Drosophila melanogaster. Previous studies have shown that the long strains (L-strain) have significantly lower levels of dopamine expression in the brain than the short strains (S-strain) and that they have an abnormal pattern of locomotor activity. Furthermore, previous studies have shown that administering dopamine to L-strain beetles reduces the duration of tonic immobility. Transcriptome analysis of brain and thorax of the L- and S-strains also showed differences in mRNA expression of genes involved in dopamine synthesis and tyrosine metabolism. These results indicate that the phenotype and molecular basis of the L-strain are similar to those of Parkinsonfs syndrome symptoms. In order to establish a link between T. castaneum and PD, we compared the DNA sequences of the L- and S-strains to human genes affecting dopaminergic pathways. The DNA comparison revealed many mutated regions in these genes in the L-strain. We discuss the relationship between dopaminergic pathway genes and PD-like phenotypes across humans, Drosophila, and the red flour beetle. en-copyright= kn-copyright= en-aut-name=TanakaKeisuke en-aut-sei=Tanaka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SasakiKen en-aut-sei=Sasaki en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YajimaShunsuke en-aut-sei=Yajima en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyatakeTakahisa en-aut-sei=Miyatake en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= affil-num=2 en-affil=Graduate School of Agriculture, Tamagawa University kn-affil= affil-num=3 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=42 end-page=50 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biosensing method of growth diagnosis in the forced culture of strawberries \Development of crop-identification algorithms\ en-subtitle= kn-subtitle= en-abstract= kn-abstract=An image-processing algorithm for identifying individual crops is developed for labor-savings and time-series biological information collection. Information including the leaf development frequency are diagnostic indicators of strawberry growth. The algorithm is designed for drones in greenhouses that cannot acquire location information using the global navigation satellite system (GNSS). Drones fly over crop rows and sequentially assign identification numbers (IDs) to crops. Object-detection artificial intelligence (AI) is used to estimate the crop zone, and the ID is based on the crops number difference between frames. The previous misdetection rate was 1.06 %, failing to identify crops, which decreases to 0.31 % using the proposed algorithm. Furthermore, because there are no failures in consecutive frames, IDs are assigned to all crops correctly. en-copyright= kn-copyright= en-aut-name=TSUBOTAShogo en-aut-sei=TSUBOTA en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NAMBAKazuhiko en-aut-sei=NAMBA en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KASEIShota en-aut-sei=KASEI en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FUKATSUTokihiro en-aut-sei=FUKATSU en-aut-mei=Tokihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Institute of Agricultural Machinery, National Agriculture and Food Research Organization kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Institute of Agricultural Machinery, National Agriculture and Food Research Organization kn-affil= affil-num=4 en-affil=Institute of Agricultural Machinery, National Agriculture and Food Research Organization kn-affil= en-keyword=strawberry kn-keyword=strawberry en-keyword=forcing culture kn-keyword=forcing culture en-keyword=image-processing kn-keyword=image-processing en-keyword=object-detection kn-keyword=object-detection en-keyword=identification of individual crops kn-keyword=identification of individual crops en-keyword=drones kn-keyword=drones END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=6 article-no= start-page=845 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Seasonal Variations in the Risk of Outpatient Acute Kidney Injury in Patients with Chronic Kidney Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Acute kidney injury (AKI) frequently occurs in the outpatient setting and is associated with adverse renal and survival outcomes. However, there is no established definition of outpatient AKI, and the risk factors, especially seasonal variation, remain limited. This study aimed to investigate seasonal variation in the risk of outpatient AKI. Methods: This retrospective observational study used routinely collected clinical laboratory data from a single hospital in Japan between 2007 and 2022. Outpatient AKI was defined as ?35% relative decline in estimated glomerular filtration rate (eGFR) compared with a preceding outpatient measurement obtained within 14?90 days. Monthly and seasonal variations in outpatient AKI risk in patients with chronic kidney disease (CKD) were evaluated using logistic regression models. Subgroup analyses were performed according to AKI stage, age group, and CKD stage. Results: A total of 203,853 outpatient records were analyzed. The incidence of outpatient AKI was highest in August and lowest in November. Analyses demonstrated significantly increased odds ratios of outpatient AKI in January, February, July, and August. Seasonally, the risk was significantly higher during the summer. Stage-specific analyses showed that AKI stage 1 was more frequent in the summer, whereas AKI stage 2 tended to increase during the winter. Conclusions: Outpatient AKI exhibits distinct seasonal patterns, with increased risk during both summer and winter and differential associations according to AKI severity and baseline kidney function. Recognition of these patterns may help identify vulnerable populations and inform targeted preventive strategies for outpatient AKI. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=acute kidney injury kn-keyword=acute kidney injury en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=outpatients kn-keyword=outpatients en-keyword=seasons kn-keyword=seasons END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=6 article-no= start-page=657 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adolescent screen use in the pre-internet era and subsequent health and well-being: an outcome-wide longitudinal study en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study used data from the National Longitudinal Study of Adolescent to Adult Health (Add Health, N?=?11,054) to assess whether increases in screen-based leisure during adolescence (Wave II, from 1996) predicted adult well-being (Wave IV, from 2008-09), adjusting for a wide range of covariates (Wave I, from 1995). Using an outcome-wide analytic approach, we examined associations between screen time and 38 adult outcomes, adjusting for prior screen time, values of most outcomes, and confounders. Most associations were null. Modest evidence was found for links between screen time (continuous) and reduced sense of control, illicit drug use, and allostatic load. High screen time (14 h/week) or more also showed weak associations with lower depression and preventive care use. Because the data predate widespread internet use, the findings help establish a baseline for the long-term effects of non-internet screen activities, which appeared to behave had limited impact on adult health and well-being. en-copyright= kn-copyright= en-aut-name=de la Rosa Fern?ndez-PachecoPedro Antonio en-aut-sei=de la Rosa Fern?ndez-Pacheco en-aut-mei=Pedro Antonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WilkinsonRenae en-aut-sei=Wilkinson en-aut-mei=Renae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CowdenRichard G. en-aut-sei=Cowden en-aut-mei=Richard G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChenYing en-aut-sei=Chen en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CaseBrendan en-aut-sei=Case en-aut-mei=Brendan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=VanderWeeleTyler J. en-aut-sei=VanderWeele en-aut-mei=Tyler J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Youth in Transition, Institute for Culture and Society, Universidad de Navarra kn-affil= affil-num=2 en-affil=Human Flourishing Program, Institute for Quantitative Social Science, Harvard University kn-affil= affil-num=3 en-affil=Human Flourishing Program, Institute for Quantitative Social Science, Harvard University kn-affil= affil-num=4 en-affil=Human Flourishing Program, Institute for Quantitative Social Science, Harvard University kn-affil= affil-num=5 en-affil=Human Flourishing Program, Institute for Quantitative Social Science, Harvard University kn-affil= affil-num=6 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Leisure kn-keyword=Leisure en-keyword=Television kn-keyword=Television en-keyword=Outcome-wide epidemiology kn-keyword=Outcome-wide epidemiology en-keyword=Video games kn-keyword=Video games en-keyword=Adolescence kn-keyword=Adolescence en-keyword=Well-being kn-keyword=Well-being 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=68 cd-vols= no-issue=3 article-no= start-page=e70044 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Simple Method for RNA-Seq of Manually Isolated Chromatophores in Oryzias Fishes en-subtitle= kn-subtitle= en-abstract= kn-abstract=RNA sequencing (RNA-seq) has become an essential tool for analyzing gene expression and exploring cell type?specific transcriptomes. However, sample preparation and quality control remain challenging, as current approaches typically rely on dissecting tissues containing mixed cell populations or using flow cytometry to isolate fluorescently labeled cells. Here we present a simple and reliable method for RNA-seq of chromatophores (pigment cells) by manually isolating cells based on their natural pigmentation. We analyzed four chromatophore types?melanophores, xanthophores, iridophores, and leucophores?in medaka (Oryzias latipes). Remarkably, as few as 100 cells per type yielded reasonably high-quality transcriptomes sufficient to identify differentially expressed genes (DEGs). Furthermore, this method was successfully applied to a non-model medaka species, O. woworae, which shares the same four chromatophore types. Our approach enables efficient, low-cost, and cross-species transcriptome analysis of chromatophores without requiring transgenic markers or flow cytometry. en-copyright= kn-copyright= en-aut-name=GodaMakoto en-aut-sei=Goda en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyagiAsuka en-aut-sei=Miyagi en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugiwakaKeisuke en-aut-sei=Sugiwaka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeMasakatsu en-aut-sei=Watanabe en-aut-mei=Masakatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Bessho]UeharaManabu en-aut-sei=Bessho]Uehara en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HibiMasahiko en-aut-sei=Hibi en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=TanakaRieko en-aut-sei=Tanaka en-aut-mei=Rieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MasengiKawilarang W. A. en-aut-sei=Masengi en-aut-mei=Kawilarang W. A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamahiraKazunori en-aut-sei=Yamahira en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=HashimotoHisashi en-aut-sei=Hashimoto en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Institute of Photonics Medicine, Hamamatsu University School of Medicine kn-affil= affil-num=2 en-affil=Institute of Photonics Medicine, Hamamatsu University School of Medicine kn-affil= affil-num=3 en-affil=Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University kn-affil= affil-num=4 en-affil=Cellular and Structural Physiology Institute (CeSPI) and Graduate School of Pharmaceutical Sciences, Nagoya University kn-affil= affil-num=5 en-affil=Frontier Research Institute for Interdisciplinary Science, Tohoku University kn-affil= affil-num=6 en-affil=Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University kn-affil= affil-num=7 en-affil=Comparative Genomics Laboratory, National Institute of Genetics kn-affil= affil-num=8 en-affil=World Medaka Aquarium, Nagoya Higashiyama Zoo and Botanical Gardens kn-affil= affil-num=9 en-affil=Faculty of Fisheries and Marine Science, Sam Ratulangi University kn-affil= affil-num=10 en-affil=Tropical Biosphere Research Center, University of the Ryukyus kn-affil= affil-num=11 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=12 en-affil=Department of Biological Science, Division of Natural Science, Graduate School of Science, Nagoya University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=1 article-no= start-page=33 end-page=44 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=Large-scale rainfall characteristics at the heavy rainfall event around the western Japan during 5?7 July 2018 kn-title=2018”N7ŒŽ5“ú?7“ú‚̼“ú–{‹‰J‚É‚¨‚¯‚éLˆæ~…“Á« en-subtitle= kn-subtitle= en-abstract= kn-abstract=@Large-scale rainfall characteristics at the heavy rainfall event around the western Japan for 5?7 July 2018 were analyzed with use of the 10-mimute precipitation data at the surface meteorological observation stations of the Japan Meteorological Agency, and so on. In this case, the area with 3 days total precipitation of near or more than 300 mm was distributed widely from northern Kyushu to Shiga and Fukui Prefectures. As in the many heavy rainfall events around Kyushu District in the mature stage of the Baiu season, contribution of the intense rainfall with more than 4 mm/10-minute (24 mm/h) attained about one third of the areal mean total precipitation. However, it is noted that the "not so intense rain" with less than 2 mm/10-minute (12 mm/h) also contributed to about one third of the huge total precipitation in the wide area. In short, this case could be characterized by the mixture of the western Japan type heavy rainfall event and the eastern Japan type one. en-copyright= kn-copyright= en-aut-name=KATOKuranoshin en-aut-sei=KATO en-aut-mei=Kuranoshin kn-aut-name=‰Á“¡“àåUi kn-aut-sei=‰Á“¡ kn-aut-mei=“àåUi aut-affil-num=1 ORCID= en-aut-name=MATSUMOTOKengo en-aut-sei=MATSUMOTO en-aut-mei=Kengo kn-aut-name=¼–{Œ’Œá kn-aut-sei=¼–{ kn-aut-mei=Œ’Œá aut-affil-num=2 ORCID= en-aut-name=OTANIKazuo en-aut-sei=OTANI en-aut-mei=Kazuo kn-aut-name=‘å’J˜a’j kn-aut-sei=‘å’J kn-aut-mei=˜a’j aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Education, Okayama University kn-affil=‰ªŽR‘åŠwŠwpŒ¤‹†‰@‹³ˆçŠwˆæi—‰Èj affil-num=2 en-affil=Okayama Gakugeikan High School kn-affil=‰ªŽRŠwŒ|ŠÙ‚“™ŠwZ affil-num=3 en-affil=TV Setouchi Broadcasting Co., LTD. kn-affil=ƒeƒŒƒr‚¹‚Æ‚¤‚¿(Š”) en-keyword=western Japan heavy rainfall in July 2018 kn-keyword=western Japan heavy rainfall in July 2018 en-keyword=10-minute precipitation data kn-keyword=10-minute precipitation data en-keyword=east-west difference of the Baiu precipitation kn-keyword=east-west difference of the Baiu precipitation END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=e72040 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Overload on Imiquimod]Induced Psoriasis Model Mice: A Basic Experimental Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Psoriasis is a skin disorder complicated by arthritis and enthesitis. The cytokines interleukin (IL)-17, IL-23, and tumor necrosis factor (TNF)-ƒ¿ are reportedly key effectors of psoriasis. Additionally, gamma delta (ƒÁƒÂ) T cells exacerbate inflammation by producing inflammatory cytokines such as IL-17 and TNF-ƒ¿. However, details regarding the mechanisms linking pathogenesis and mechanical stress remain unclear. This study aimed to investigate the effect of strenuous exercise on the pathology of psoriasis using mouse models of imiquimod (IMQ)-induced psoriasis.
Methods: Twenty mice were randomly assigned to four groups: IMQ???TRED? (control), IMQ???TRED+ (treadmill running mice), IMQ?+?TRED? group (IMQ treated mice), and IMQ?+?TRED+ group (IMQ treated and treadmill running mice). The tissue sections from back skin and thymus were immunostained with antibodies against IL-17, IL-23, and ƒÁƒÂ T cells. Shoulder sections were stained using hematoxylin and eosin, and Toluidine Blue and Picrosirius Red. Additionally, the shoulder tissue sections were immunostained with antibodies against TNF-ƒ¿ and matrix metalloproteinase (MMP)-13. Serum cytokine level was measured to evaluate systemic inflammation.
Results: Strenuous exercise exacerbated pathological changes associated with psoriasis, including increased ƒÁƒÂ T cell infiltration and upregulated IL-17 and IL-23 expression in the skin, as well as enhanced ƒÁƒÂ T cell development and IL-17 expression in the thymus. Although strenuous exercise did not further worsen the modified PASI scores, histological and immunological markers of inflammation were significantly enhanced. Serum levels of TNF-ƒ¿ and IL-17 were significantly elevated in IMQ-induced psoriasis model mice. Moreover, pathological changes induced by strenuous exercise were observed in the enthesis, including angiogenesis and upregulated expression of TNF-ƒ¿ and MMP-13.
Conclusion: This study revealed that strenuous exercise exacerbates pathological changes in IMQ-induced psoriasis model mice. en-copyright= kn-copyright= en-aut-name=FurutaniTomoki en-aut-sei=Furutani en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoTaichi en-aut-sei=Saito en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkedaAsahi en-aut-sei=Ikeda en-aut-mei=Asahi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MashimaKenta en-aut-sei=Mashima en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YukihiroNatsumi en-aut-sei=Yukihiro en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KusakabeSatoki en-aut-sei=Kusakabe en-aut-mei=Satoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamichiRyo en-aut-sei=Nakamichi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro 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=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University 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=Okayama University Medical School Faculty of Medicine kn-affil= affil-num=4 en-affil=Okayama University Medical School Faculty of Medicine kn-affil= affil-num=5 en-affil=Okayama University Medical School Faculty of Medicine kn-affil= affil-num=6 en-affil=Okayama University Medical School Faculty of Medicine Okayama Japan kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=enthesis kn-keyword=enthesis en-keyword=psoriasis kn-keyword=psoriasis en-keyword=strenuous exercise kn-keyword=strenuous exercise END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=e70168 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanosensitive Ion Channel PIEZO1 Suppresses BMP2-Induced Ossification of the Annulus Fibrosus Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Major cause of low-back pain is intervertebral disc degeneration (IVDD), with mechanical stress playing a crucial role in its progression. A mechanosensitive ion channel, PIEZO1, is involved in various musculoskeletal tissues, but its role in the annulus fibrosus (AF) remains unclear. This study aimed to elucidate the function of PIEZO1 in AF cells under mechanical stimulation.
Methods: Primary rat AF cells were subjected to cyclic tensile strain (CTS) at low (2%) and high (12%) strain levels to investigate strain-dependent effects on osteogenic gene expression. We evaluated the effects of Piezo1, Piezo2, and Trpv4 knockdown by RNA interference to identify the upstream mechanotransducer. Furthermore, PIEZO1 was activated using the agonist Yoda1, followed by RNA-sequencing analysis and evaluation of its effects on BMP2-induced osteogenesis in rat AF cells. We also examined the effects of Yoda1 in primary human AF cells.
Results: Low-strain CTS significantly suppressed osteogenic marker expression, which was not observed with high strain. Piezo1 knockdown reversed this suppression, whereas Piezo2 and Trpv4 had no effect. Piezo1 activation by Yoda1 produced similar anti-osteogenic effects in both rat and human AF cells. RNA sequencing revealed the enrichment of ossification and calcineurin signaling pathways in rat cells. Furthermore, Piezo1 activation inhibited BMP2-induced osteogenesis and nuclear translocation of p-Smad1/5/9.
Conclusions: Piezo1 maintains AF cell homeostasis under mechanical stress by suppressing osteogenic changes via calcineurin-mediated inhibition of BMP signaling, which may represent a novel therapeutic target for IVDD. en-copyright= kn-copyright= en-aut-name=ShitozawaHisakazu en-aut-sei=Shitozawa en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamichiRyo en-aut-sei=Nakamichi en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UedaMasataka en-aut-sei=Ueda en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoTaichi en-aut-sei=Saito en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OdaYoshiaki en-aut-sei=Oda en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakatoriRyo en-aut-sei=Takatori en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, 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 Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=annulus fibrosus kn-keyword=annulus fibrosus en-keyword=calcification kn-keyword=calcification en-keyword=ossification kn-keyword=ossification en-keyword=PIEZO1 kn-keyword=PIEZO1 END start-ver=1.4 cd-journal=joma no-vol=57 cd-vols= no-issue=3 article-no= start-page=93 end-page=109 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Environmental Conservation Costs and Operational Efficiency: Evidence from Japanese Manufacturing Firms en-subtitle= kn-subtitle= en-abstract= kn-abstract=@This study investigates whether environmental conservation costs (ECC) support the operational effectiveness and financial stability of Japanese manufacturing firms. Using a balanced panel of 128 non-financial companies listed on the Tokyo Stock Exchange from 2010 to 2022, we manually collected firm-level ECC data based on the Ministry of the Environment, Japan's guidelines from sustainability reports and matched them with financial data from Compustat Global/S&P Capital IQ. Applying pooled ordinary least squares regression with firm-level clustered standard errors and winsorized variables, we examine two aspects of performance as measures of operating efficiency and profitability: asset turnover and profit margin. The results show that ECC is positively associated with asset turnover and profit margin, and that the effect is stronger in more profitable companies, substantiating the Resource-Based View that green practices generate competitiveness. These findings contribute to sustainability finance research by going beyond perceptual measures of environmental, social, and governance ratings, and measuring actual firm-level spending on environmental activities, thereby providing more nuanced insights into how environmental practices translate into actual financial performance. This study offers clear managerial and policy implications by showing that transparent environmental conservation costs improve disclosure quality and serve as a measure of improved efficiency and profitability. en-copyright= kn-copyright= en-aut-name=NazirYusra en-aut-sei=Nazir en-aut-mei=Yusra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TennojiyaTatsumasa en-aut-sei=Tennojiya en-aut-mei=Tatsumasa kn-aut-name=“V‰¤Ž›’J’B« kn-aut-sei=“V‰¤Ž›’J kn-aut-mei=’B« aut-affil-num=2 ORCID= affil-num=1 en-affil=Doctoral student at Graduate school of humanities and social sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of humanities and social sciences, Okayama University kn-affil= en-keyword=Environmental Accounting kn-keyword=Environmental Accounting en-keyword=Environmental Conservation Cost, Operating Efficiency kn-keyword=Environmental Conservation Cost, Operating Efficiency en-keyword=Profitability kn-keyword=Profitability en-keyword=Asset Turnover kn-keyword=Asset Turnover en-keyword=Sustainability kn-keyword=Sustainability en-keyword=Japanese Manufacturing Companies kn-keyword=Japanese Manufacturing Companies en-keyword=Resource-Based View kn-keyword=Resource-Based View END start-ver=1.4 cd-journal=joma no-vol=57 cd-vols= no-issue=3 article-no= start-page=11 end-page=40 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Network Analysis of Interregional Information Exchange: A Study in the Takahashi River Basin Area kn-title=’nˆæŠÔ‚Å‚Ìî•ñŒð—¬‚ÉŠÖ‚·‚éƒlƒbƒgƒ[ƒN•ªÍF‚—Àì—¬ˆæŒ—‚Å‚Ì’²¸‚É‚æ‚é en-subtitle= kn-subtitle= en-abstract=@This paper conducted network analysis focusing on information exchange among participating entities in the "Takahashi River Basin Economic Growth Strategy Council," operating within Okayama Prefecture's "Takahashi River Basin Core City Area." The Takahashi River Basin Collaborative Core City Areai Takahashi River Basin Areajis a collaborative core city area encompassing ten municipalities located around the Takahashi River in Okayama Prefecture: Niimi City, Takahashi City, Soja City, Hayashima Town, Kurashiki City, Yakage Town, Ibara City, Asakuchi City, Satosho Town, and Kasaoka City. For the network analysis within the Takahashi River Basin Area, projects implemented within the area were classified into eight categories. A questionnaire survey was conducted regarding information exchange among participating entities for each project. Network metrics included calculating centrality indicesi degree centrality and betweenness centralityj for each project, along with density, transitivity, and reciprocity. By project type, tourism projects exhibited the densest network structure for information exchange. From a network perspective, tourism projects can be considered the most actively pursued initiative within the Takahashi River Basin area. Furthermore, across all projects, centrality indicators for specific administrative bodies and regional economic organizations, such as chambers of commerce and industry, generally showed high values. This clearly indicates their function as hubs for information exchange and as entities concentrating or dispersing information within the network. Based on the results of network analysis, two recommendations for future regional development in the Takahashi River Basin were proposed from a network perspective. The first is to aim for dense networks across all businesses by sharing the roles of information exchange hubs and information concentration/distribution entities among the entities involved, depending on the business. The second is to aim for a dense network overall by eliminating entities that are not participating at all in the Takahashi River Basin's information exchange network. kn-abstract=@–{e‚Å‚ÍC‰ªŽRŒ§‚Ìu‚—Àì—¬ˆæ˜AŒg’†•“sŽsŒ—v‚Å2014”N‚©‚çŠJ³‚ê‚Ä‚¢‚éu‚—Àì—¬ˆæŒoϬ’·í—ª‰ï‹cv‚É‚¨‚¯‚éŽQ‰ÁŽå‘ÌŠÔ‚Ìî•ñŒð—¬‚ɂ‚¢‚Ẵlƒbƒgƒ[ƒN•ªÍ‚ðs‚Á‚½B‚—Àì—¬ˆæ˜AŒg’†•“sŽsŒ—i‚—Àì—¬ˆæŒ—j‚Æ‚ÍC‰ªŽRŒ§‚—ÀìŽü•Ó‚Ɉʒu‚·‚錻݂ÌVŒ©ŽsC‚—ÀŽsC‘ŽÐŽsC‘“‡’¬C‘q•~ŽsC–îŠ|’¬CˆäŒ´ŽsCóŒûŽsC—¢¯’¬CŠ}‰ªŽs‚Ì10Ž©Ž¡‘Ì‚ªŽQ‰Á‚µ‚Ä‚¢‚é˜AŒg’†•“sŽsŒ—‚Å‚ ‚éB‚—Àì—¬ˆæŒ—‚É‚¨‚¯‚éƒlƒbƒgƒ[ƒN•ªÍ‚ÉÛ‚µ‚Ä‚ÍC“¯Œ—ˆæ“à‚Å“WŠJ‚³‚ê‚Ä‚¢‚鎖‹Æ‚ð‚W‚‚ɕª—Þ‚µC‚»‚ꂼ‚ê‚ÌŽ–‹Æ‚ÉŠÖ‚·‚éŽQ‰ÁŽå‘ÌŠÔ‚Ìî•ñŒð—¬‚ɂ‚¢‚ăAƒ“ƒP[ƒg’²¸‚ðs‚Á‚½Bƒlƒbƒgƒ[ƒNŽw•W‚ɂ‚¢‚Ä‚ÍŽ–‹Æ‚²‚Æ‚ÉŽŸ”’†S«‚Æ”}‰î’†S«‚Ì’†S«Žw•W‚ðC‚Ü‚½Ž–‹Æ•Ê‚É–§“xC„ˆÚ«C‘ŠŒÝ«‚ðŽZo‚µ‚½BŽ–‹Æ•Ê‚É‚Ý‚é‚ÆCŠÏŒõŽ–‹Æ‚ɂ‚¢‚Ä‚Ìî•ñŒð—¬‚ªÅ‚à–§‚ȃlƒbƒgƒ[ƒN\‘¢‚ð‚µ‚Ä‚¨‚èCƒlƒbƒgƒ[ƒN‚ÌŽ‹“_‚Å‚ÍŠÏŒõŽ–‹Æ‚ª‚—Àì—¬ˆæŒ—“à‚Åłਗ͓I‚És‚í‚ê‚Ä‚¢‚鎖‹Æ‚Æ‚¢‚¦‚éB‚Ü‚½‘SŽ–‹Æ‚É‚¨‚¢‚Ä“Á’è‚Ìs­Žå‘Ì‚â¤H‰ï‹cŠ‚ð‚Í‚¶‚ß‚Æ‚·‚é’nˆæŒoÏ’c‘Ì“™‚Ì’†S«Žw•W‚ª‘S‘Ì“I‚É‘å‚«‚È’l‚ð‚Æ‚Á‚Ä‚¨‚èCƒlƒbƒgƒ[ƒN‚É‚¨‚¢‚Äî•ñŒð—¬‚̃nƒu‚âî•ñ‚ÌW’†E•ªŽUŽå‘Ì‚Æ‚µ‚Ä‹@”\‚µ‚Ä‚¢‚邱‚Æ‚ª–¾‚ç‚©‚É‚È‚Á‚½B•ªÍŒ‹‰Ê‚𓥂܂¦Cƒlƒbƒgƒ[ƒN‚ÌŽ‹“_‚©‚ç‚—Àì—¬ˆæŒ—‚Ì¡“x‚Ì’nˆæU‹»‚ɂ‚¢‚Ä‚Q“_’ñŒ¾‚µ‚½B‚P‚‚͎–‹Æ‚É‚æ‚Á‚Äî•ñŒð—¬‚̃nƒu‚âî•ñ‚ÌW’†E•ªŽUŽå‘Ì‚ðŽå‘ÌŠÔ‚Å•ª’S‚·‚邱‚Æ‚É‚æ‚Á‚ÄC‚·‚ׂĂ̎–‹Æ‚Å–§‚ȃlƒbƒgƒ[ƒN‚ð’z‚­‚±‚Æ‚ð–ÚŽw‚·‚±‚Æ‚Å‚ ‚éB‚à‚¤‚P‚‚͂—Àì—¬ˆæŒ—‚Ìî•ñŒð—¬ƒlƒbƒgƒ[ƒN‚É‘S‚­ŽQ‰Á‚µ‚Ä‚¢‚È‚¢Žå‘Ì‚ð‚È‚­‚·‚±‚Æ‚ÅC‘S‘Ì“I‚É–§‚ȃlƒbƒgƒ[ƒN‚ð–ÚŽw‚·‚±‚Æ‚Å‚ ‚éB en-copyright= kn-copyright= en-aut-name=NakamuraRyohei en-aut-sei=Nakamura en-aut-mei=Ryohei kn-aut-name=’†‘º—Ç•½ kn-aut-sei=’†‘º kn-aut-mei=—Ç•½ aut-affil-num=1 ORCID= en-aut-name=YokotaNatsumi en-aut-sei=Yokota en-aut-mei=Natsumi kn-aut-name=‰¡“c‰ÄŽÀ kn-aut-sei=‰¡“c kn-aut-mei=‰ÄŽÀ aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=‰ªŽR‘åŠw affil-num=2 en-affil= kn-affil=‰ºŠÖŽs–ðŠ END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=9 article-no= start-page=e772 end-page=e780 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Aging of the tricuspid valve annulus detected by photon-counting detector computed tomography: Importance of aortic root compression on occurrence of arrhythmias en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The aortic root compresses the heart in elderly patients, potentially influencing the conduction system and causing atrial tachyarrhythmias. However, actual anatomic alterations in the right side of the heart because of aortic root compression have not yet been fully evaluated.
Objective This study aimed to elucidate the alterations in the tricuspid valve annulus (TVA) caused by aortic root compression using a 3-dimensional endoscopic view of the heart constructed by photon-counting detector computed tomography, an emerging medical technology.
Methods We analyzed 147 consecutive patients who underwent photon-counting detector computed tomography at our institute after excluding those with diseases that directly influenced the right side of the heart.
Results Aortic root compression caused significant TVA deformation. We defined severe TVA compression as the length of the TVA compressed by the aortic root ?80% of the major axis of the TVA. Severe compression was more prevalent in elderly patients (age ?75 years [44%]; P < .01). The distance between the membranous septum and ostium of the coronary sinus was shortened, whereas the cavotricuspid isthmus was elongated in older patients. The regression analysis identified aging as a significant contributor to TVA compression. The short minor and long major axes of the TVA, incidence of atrial tachyarrhythmias (74% vs 45%; P < .01), and atrioventricular conduction disturbances (35% vs 15%; P < .01) were more frequently observed in patients with severe compression.
Conclusion Aortic root compression deforms the TVA and alters the anatomic relationship between the atrioventricular conduction system and the cavotricuspid isthmus. Therefore, aortic root compression may contribute to the occurrence of atrial tachyarrhythmias and conduction disturbances in older patients. en-copyright= kn-copyright= en-aut-name=MoritaHiroshi en-aut-sei=Morita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaseSatoshi en-aut-sei=Nagase en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimotoYoshihisa en-aut-sei=Morimoto en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasudaTakuro en-aut-sei=Masuda en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UeokaAkira en-aut-sei=Ueoka en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AsadaSaori en-aut-sei=Asada en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoMasakazu en-aut-sei=Miyamoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishiiNobuhiro en-aut-sei=Nishii en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=3 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center 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, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=11 en-affil=Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and Dentistry kn-affil= en-keyword=Tricuspid valve annulus kn-keyword=Tricuspid valve annulus en-keyword=Aortic root kn-keyword=Aortic root en-keyword=Photon-counting detector computed tomography kn-keyword=Photon-counting detector computed tomography en-keyword=Atrial tachyarrhythmia kn-keyword=Atrial tachyarrhythmia en-keyword=Conduction abnormality kn-keyword=Conduction abnormality END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue= article-no= start-page=101798 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=Alcohol consumption, smoking, and the implications of their cessations for field carcinogenesis in the esophagus: a 10-year prospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Alcohol and tobacco are established carcinogens, which promote field carcinogenesis for esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the long-term effects of alcohol and tobacco cessations, and background mucosal status, on risk for metachronous ESCC (mESCC) after endoscopic resection (ER).
Methods This was a multicentre prospective cohort study of patients with intramucosal ESCC treated by ER. All participants received structured education on cessation, and underwent regular endoscopic surveillance. Patients were stratified by Lugol-voiding lesion (LVL) grade (A: none, B: 1?9, C: ?10). The impacts of alcohol and smoking cessation on field carcinogenesis were assessed.
Findings Among 331 enrolled patients, the median follow-up was 120 months (range: 1.3?176.9). The cumulative incidences of mESCC were 10.4%, 27.2%, and 61.8% in grades A, B, and C, respectively. An increment of 1 unit (22 g ethanol) of alcohol consumption and higher LVL grade independently increased the risk for mESCC. Alcohol or smoking cessation reduced this risk (hazard ratio [HR] 0.52, 95% confidence interval [CI]: 0.31?0.88; HR 0.44, 95% CI: 0.25?0.78, respectively), and combined cessation had the greatest impact (HR 0.21, 95% CI: 0.07?0.65). Complete cessation, rather than partial reduction, was necessary to achieve meaningful risk reduction.
Interpretation Alcohol and tobacco exposure, and a large number of LVL, are major determinants of mESCC. Complete cessation markedly reduces risk, underscoring the importance of behavioural interventions for secondary prevention of field carcinogenesis after ER. en-copyright= kn-copyright= en-aut-name=KatadaChikatoshi en-aut-sei=Katada en-aut-mei=Chikatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokoyamaTetsuji en-aut-sei=Yokoyama en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanoTomonori en-aut-sei=Yano en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FurueYasuaki en-aut-sei=Furue en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiHaruhisa en-aut-sei=Suzuki en-aut-mei=Haruhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshidoKenji en-aut-sei=Ishido en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoKeiko en-aut-sei=Yamamoto en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanishiHiroyoshi en-aut-sei=Nakanishi en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KoikeTomoyuki en-aut-sei=Koike en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TamaokiMasashi en-aut-sei=Tamaoki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawataNoboru en-aut-sei=Kawata en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HiraoMotohiro en-aut-sei=Hirao en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=OgataTakashi en-aut-sei=Ogata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KatagiriAtsushi en-aut-sei=Katagiri en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamanouchiTakenori en-aut-sei=Yamanouchi en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiyokawaHirofumi en-aut-sei=Kiyokawa en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawakuboHirofumi en-aut-sei=Kawakubo en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KonnoMaki en-aut-sei=Konno en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OhashiShinya en-aut-sei=Ohashi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OmoriTai en-aut-sei=Omori en-aut-mei=Tai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ShimodaTadakazu en-aut-sei=Shimoda en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=OchiaiAtsushi en-aut-sei=Ochiai en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=IshikawaHideki en-aut-sei=Ishikawa en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=YokoyamaAkira en-aut-sei=Yokoyama en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=MutoManabu en-aut-sei=Muto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Department of Medical Oncology, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Health Promotion, National Institute of Public Health kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Department of Endoscopy, Saitama Cancer Center kn-affil= affil-num=5 en-affil=Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=7 en-affil=Division of Endoscopy, Hokkaido University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Ishikawa Prefectural Central Hospital kn-affil= affil-num=9 en-affil=Division of Gastroenterology, Tohoku University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Medical Oncology, Kyoto University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Division of Endoscopy, Shizuoka Cancer Center kn-affil= affil-num=12 en-affil=Department of Surgery, NHO Osaka National Hospital kn-affil= affil-num=13 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Gastrointestinal Surgery, Kanagawa Cancer Center kn-affil= affil-num=15 en-affil=Division of Gastroenterology, Department of Medicine, Showa Medical University Hospital kn-affil= affil-num=16 en-affil=Department of Gastroenterology, Kumamoto Regional Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=18 en-affil= kn-affil= affil-num=19 en-affil=Department of Gastroenterology, Tochigi Cancer Center kn-affil= affil-num=20 en-affil=Department of Medical Oncology, Kyoto University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Medical Oncology, Kyoto University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Department of Surgery, Kawasaki Municipal Kawasaki Hospital kn-affil= affil-num=23 en-affil=Department of Diagnostic Pathology, Shizuoka Cancer Center kn-affil= affil-num=24 en-affil=Exploratory Oncology Research and Clinicai Trial Center, National Cancer Center kn-affil= affil-num=25 en-affil=Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine kn-affil= affil-num=26 en-affil=Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center kn-affil= affil-num=27 en-affil=Department of Medical Oncology, Kyoto University Graduate School of Medicine kn-affil= en-keyword=Esophageal squamous cell carcinoma kn-keyword=Esophageal squamous cell carcinoma en-keyword=Field carcinogenesis kn-keyword=Field carcinogenesis en-keyword=Metachronous cancer kn-keyword=Metachronous cancer en-keyword=Alcohol kn-keyword=Alcohol en-keyword=Tobacco kn-keyword=Tobacco en-keyword=Lugol-voiding lesion kn-keyword=Lugol-voiding lesion END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MMP-3 cleavage of Lamin A induces pro-migratory nuclear deformity, nucleophagy, and their autophagic secretion with extracellular vesicles in metastatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that cleave a plethora of substrates, including components of the extracellular matrix and cell-surface-associated proteins, as well as intracellular targets. MMPs have also been found in extracellular vesicles (EVs), such as exosomes. MMP-3 promotes tumor growth, epithelial-to-mesenchymal transition, genome instability, migration, invasion, and metastasis of cancer cells, and nuclear MMP-3 controls gene transcription. Intranuclear proteolysis by MMPs may significantly alter cancer progression. However, the nuclear substrates of MMP-3 have not been well investigated. In this study, we performed proteomic analyses to identify the nuclear substrates and EV proteins regulated by MMP-3. While rabidly metastatic colon cancer (LuM1) three-dimensionally cultured tumoroids secreted EVs containing 30 protein types, including Lamin A (LMNA), MMP-3, fibronectin (FN1), HSPA8 (Hsc70), ƒÀ-actin (ACTB), and vimentin (VIM), CRISPR/Cas9-based knockout of MMP-3 reduced the secretion of these proteins in EVs. Notably, EV-bound cleaved Lamin secretion was confirmed by immunoelectron microscopy. Also, MMP-3 formed proteolytic dimers via its hemopexin-like repeat domains in nuclei. Many nuclear MMP-3-binding proteins, including Lamin A/C, histones, topoisomerases, and hnRNPs, were screened by co-immunoprecipitation followed by proteomics. Proteolytic MMP-3 overexpression generated a C-terminal 30-kDa fragment of Lamin A, whose cleavage site was defined via structural analysis. MMP-3 digestion of Lamin A induced nuclear deformity (atypia) required for cell migration in confined space. The cleaved Lamin A and MMP-3 were transported with autophagosomes (LC3B+), nucleophagosomes, and amphisomes (CD63?+?LC3B+) and co-secreted with EVs. Proteolytic MMP-3 also induced nuclear speckles of Lamin A, suggesting their roles in transcription and splicing. Clinical analysis revealed that high expressions of MMP3 and LMNA were significantly seen in head and neck squamous cell carcinoma (HNSC) than in the other 16 cancer types, and predicted poor prognosis of patients suffering from HNSC, pancreatic, rectum and lung adenocarcinomas at specific stages. Immunohistochemistry revealed that nuclear MMP-3 and cleaved Lamin were significantly higher expressed in stage IV metastatic HNSC cases than in stage I non-metastatic cases. Taken together, MMP3-cleavage of Lamin A induces nuclear deformity, nucleophagy, and their autophagic co-secretion with EVs in metastatic cancer. Also, high expression of MMP-3 and secretion of Lamin A can predict poor prognosis in multiple cancer types at specific stages. 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=TahaEman A. en-aut-sei=Taha en-aut-mei=Eman A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TiwariVikas en-aut-sei=Tiwari en-aut-mei=Vikas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueTomohiro en-aut-sei=Inoue en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=XingLizi en-aut-sei=Xing en-aut-mei=Lizi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkamotoKuniaki en-aut-sei=Okamoto en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biochemistry, Faculty of Science, Ain Shams University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Council of Scientific & Industrial Research-Indian Institute of Toxicological Research kn-affil= affil-num=5 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology kn-affil= affil-num=9 en-affil=Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=Lamin A (LMNA) kn-keyword=Lamin A (LMNA) en-keyword=Matrix metalloprotease (MMP) kn-keyword=Matrix metalloprotease (MMP) en-keyword=Proteolysis kn-keyword=Proteolysis en-keyword=Extracellular vesicle (EV) kn-keyword=Extracellular vesicle (EV) en-keyword=Exosome kn-keyword=Exosome en-keyword=Autophagy kn-keyword=Autophagy en-keyword=Amphisome kn-keyword=Amphisome en-keyword=Proteome kn-keyword=Proteome en-keyword=Nuclear deformity kn-keyword=Nuclear deformity en-keyword=Migration kn-keyword=Migration en-keyword=Metastatic cancer kn-keyword=Metastatic cancer en-keyword=Head and neck squamous cell carcinoma kn-keyword=Head and neck squamous cell carcinoma en-keyword=Colorectal cancer kn-keyword=Colorectal cancer END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=5 article-no= start-page=2339 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Concentration-Dependent Synergistic Interfacial Interactions Between Multifunctional Acrylate and Silane Coupling Agents in an Organic?Inorganic Nanohybrid Material en-subtitle= kn-subtitle= en-abstract= kn-abstract=Synergistic effects of a multifunctional acrylate and a long-chain silane coupling agent were investigated in an organic?inorganic nanohybrid material. We tested the bond strength of nanohybrid composites treated with experimental primers containing silane coupling agents?3-methacryloxypropyl trimethoxysilane (ƒÁ-MPTS) or 8-methacryloxyoctyl trimethoxysilane (8-MOTS)?with or without multifunctional acrylates?trimethylolpropane triacrylate (A-TMPT) or dipentaerythritol hexaacrylate (A-DPH). Shear bond strength was evaluated after 24 h of water storage at 37 ‹C. Untreated control and silane-only groups exhibited low shear bond strengths (e.g., control: 2.4 } 2.0 MPa) and failed exclusively at the adhesive interface. While addition of A-TMPT did not significantly improve bond strength, addition of A-DPH produced significantly higher shear bond strengths. Highest strength was achieved with 30% 8-MOTS and A-DPH (22.4 } 6.1 MPa), followed by 20% ƒÁ-MPTS and A-DPH (19.0 } 7.0 MPa), and A-DPH groups produced cohesive failures. Regardless of the silane used (ƒÁ-MPTS or 8-MOTS), incorporating A-DPH in the primer consistently yielded superior bond strengths, indicating a promising strategy for improved adhesion for such nanohybrid systems. These findings provide new insights into optimizing resin?filler interfacial interactions and may contribute to the development of restorative materials with improved long-term clinical durability. en-copyright= kn-copyright= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IrieMasao en-aut-sei=Irie en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KodamaNaoki en-aut-sei=Kodama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshizaneMai en-aut-sei=Yoshizane en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkiyamaKentaro en-aut-sei=Akiyama en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=2 en-affil=Health Research Institute, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=3 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University kn-affil= affil-num=5 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=6 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=silane coupling kn-keyword=silane coupling en-keyword=multifunctional acrylate kn-keyword=multifunctional acrylate en-keyword=bond strength kn-keyword=bond strength en-keyword=resin kn-keyword=resin END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=e79545 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prescription Support Practice for Pharmacy Students: Pre-Post Educational Intervention Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: In the field of team-based care, pharmacists are vital for optimizing medication therapy. However, many medical professionals lack the opportunity to learn how to propose prescription changes with precision.
Objective: This study aimed to address this knowledge gap by developing and assessing a new educational program for pharmacy students focused on prescription support and interprofessional collaboration.
Methods: We recruited 191 fifth-year pharmaceutical students during the 2022]2024 academic years. The program featured a 7-day intensive curriculum that included learning how to assist with prescriptions, analyzing clinical data, and engaging in role-playing exercises. A web-based questionnaire and a paper test were used to evaluate studentsf awareness and knowledge both before and after the program. Statistical analyses were performed to verify the significance of changes; we utilized the Wilcoxon signed-rank test for the ordinal data derived from the specific behavioral objectives and 2-tailed paired t tests for the interval data from the knowledge tests. The magnitude of change was quantified using r for Wilcoxon tests and Cohen dz for 2-tailed t tests, with 95% CI calculated to ensure the stability and reliability of the observed results.
Results: Analysis of the primary outcome specific behavioral objectives revealed statistically significant effects across all items (Wilcoxon signed-rank test; P<.001). Effect sizes (r=0.505]0.835) ranged from moderate to large, with particularly large effects observed in identifying contents issue (r=0.835, 95% CI 0.126-0.330; P<.001). Knowledge test scores showed significant improvement in the following 3 subjects: pharmacology (r=?0.504, 95% CI ?0.215 to 0.127; P<.001), organic chemistry (r=0.254, 95% CI ?0.148 to ?0.193; P=.004), and communication (r=0.221, 95% CI ?0.151 to ?0.190; P=.01). No significant changes were observed in pathology or pharmacokinetics.
Conclusions: This program provides strong evidence that practical, hands-on learning with hospital pharmacists helps improve pharmacy studentsf professional skills and optimize pharmaceutical therapies in interprofessional care. By teaching pharmacists to effectively propose prescription changes, the program equips them to become integral members of interprofessional care, ultimately leading to optimized pharmaceutical care for patients. en-copyright= kn-copyright= en-aut-name=AizawaFuka en-aut-sei=Aizawa en-aut-mei=Fuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YagiKenta en-aut-sei=Yagi en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HigashionnaTsukasa en-aut-sei=Higashionna en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiShimon en-aut-sei=Takahashi en-aut-mei=Shimon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShinomiyaKazuaki en-aut-sei=Shinomiya en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GodaMitsuhiro en-aut-sei=Goda en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawadaKei en-aut-sei=Kawada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=6 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Care and Clinical Pharmacy, Tokushima Bunri University kn-affil= affil-num=8 en-affil=Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=10 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=11 en-affil=Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital kn-affil= en-keyword=academic detailing kn-keyword=academic detailing en-keyword=pharmaceutical clinical practice kn-keyword=pharmaceutical clinical practice en-keyword=prescription support kn-keyword=prescription support en-keyword=professional education kn-keyword=professional education en-keyword=Interprofessional care kn-keyword=Interprofessional care END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=2 article-no= start-page=199 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Targeting the Gut in Sepsis: Therapeutic Potential of Medical Gases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, often resulting in multiorgan dysfunction. Among affected systems, the gastrointestinal tract plays a central role in sepsis progression by promoting systemic inflammation through impaired barrier function, immune imbalance, and microbiome alterations. Recent research has identified selected medical gases and gasotransmitters as promising therapeutic candidates for preserving gut integrity in sepsis. In particular, hydrogen, carbon monoxide, and hydrogen sulfide exhibit antioxidative, anti-inflammatory, and cytoprotective properties. These gases act through defined molecular pathways, including activation of Nrf2, inhibition of NF-ƒÈB, and preservation of tight junction integrity, thereby supporting intestinal barrier function. In addition, they influence immune cell phenotypes and autophagy, with indirect effects on the gut microbiome. Although most supporting evidence derives from preclinical models, translational findings and emerging safety data highlight the potential of gut-targeted gas-based strategies. This review summarizes current mechanistic and translational evidence for gut-protective medical gases in sepsis and discusses their integration into future organ-specific and mechanism-based therapeutic approaches. 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=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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= en-keyword=carbon monoxide kn-keyword=carbon monoxide en-keyword=gastrointestinal tract kn-keyword=gastrointestinal tract en-keyword=gut kn-keyword=gut en-keyword=hydrogen kn-keyword=hydrogen en-keyword=hydrogen sulfide kn-keyword=hydrogen sulfide en-keyword=sepsis kn-keyword=sepsis en-keyword=septic shock kn-keyword=septic shock 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=2026 dt-pub=20260203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world six-month outcomes after switching from aflibercept 2 mg to aflibercept 8 mg for neovascular age-related macular degeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose To investigate 6-month outcomes in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept 2 mg to intravitreal aflibercept 8 mg.
Study design Retrospective observational study.
Methods We reviewed records of consecutive nAMD eyes switched from aflibercept 2 mg to 8 mg. In eyes continuing aflibercept 8 mg, best-corrected visual acuity (BCVA), treatment intervals, and anatomical/exudative parameters were evaluated at 6 months. In eyes that could not continue, reasons for discontinuation were examined.
Results Forty-four eyes from 44 patients were included. At 6 months, 35 eyes (79.5%) continued and 9 (20.5%) discontinued aflibercept 8 mg. Discontinuing eyes had significantly shorter pre-switch treatment intervals and more frequent prior therapies than continuing eyes. In the continuation group, BCVA remained stable (median 0.05 to 0.00 logMAR, P = 0.351), while the treatment interval was significantly extended (median 7.0 to 9.0 weeks, P < 0.001). Central retinal thickness and pigment epithelial detachment height decreased significantly (P = 0.035 and P = 0.021, respectively). The proportion of eyes with subretinal fluid significantly decreased from 74.3 to 37.1% (P = 0.003). Of the discontinuations, 4 were due to worsening exudation and 5 to inability to extend to ?8 weeks as required by labeling. No intraocular inflammation or serious adverse events occurred.
Conclusions Switching to aflibercept 8?mg achieved anatomical improvements and longer treatment intervals in ~80% of nAMD cases, suggesting it may be a useful alternative to aflibercept 2 mg. However, continuation may be difficult in refractory cases requiring frequent injections before switching. en-copyright= kn-copyright= en-aut-name=KindoHiroya en-aut-sei=Kindo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HosokawaMio Morizane en-aut-sei=Hosokawa en-aut-mei=Mio Morizane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OuchiChihiro en-aut-sei=Ouchi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HayashiJunko en-aut-sei=Hayashi en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Aflibercept 8 mg kn-keyword=Aflibercept 8 mg en-keyword=Neovascular age-related macular degeneration kn-keyword=Neovascular age-related macular degeneration en-keyword=Treat-and-extend kn-keyword=Treat-and-extend en-keyword=Switching kn-keyword=Switching en-keyword=Treatment interval kn-keyword=Treatment interval END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=888 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Skeletal muscle remodelling relies on muscle stem cells (MuSCs) for regeneration after injury and hypertrophy in response to mechanical loading. However, the mechanisms that trigger MuSC activation and proliferation remain unclear. Transient receptor potential vanilloid 2 (TRPV2) ion channels respond to insulin-like growth factor-1 and mechanical stimuli to regulate the biological characteristics of various cells. Using a temporally inducible MuSC-specific conditional knockout (cKO) mouse, we show that TRPV2 regulates MuSC function and is essential for muscle remodelling. In cultured myofibre, MuSCs express TRPV2 and exhibit Ca2+ responses to the TRPV2 agonists 2-aminoethoxydiphenyl borate and probenecid, which are abolished upon TRPV2 deletion. TRPV2-deficient MuSCs exhibit reduced paired box 7 (Pax7) expression and impaired proliferation, suggesting TRPV2 is a factor that regulates the early stage of MuSC function. Myotube formation in MuSCs was enhanced by overexpression of TRPV2 and suppressed by TRPV2 deficiency, suggesting that TRPV2 is a factor that promotes myogenesis. Muscle-administered cardiotoxin promoted muscle regeneration and resulted in the appearance of numerous Pax7-positive MuSCs between myofibres. MuSC-specific TRPV2 cKO mice exhibit substantially impaired muscle regeneration after cardiotoxin-induced injury, drastically reducing Pax7-positive MuSCs between myofibres. In floxed mice, mechanical loading via synergist ablation induces hypertrophy and greatly increases the number of myonuclei per myofibre. In contrast, MuSC-specific TRPV2 cKO mice show no changes in myofibre thickness or nuclear number, either at baseline or after mechanical loading. Mechanical loading of floxed mice increased TRPV2+/Pax7+ double-positive MuSCs, but MuSC-specific TRPV2 cKO mice showed no change. Additionally, MuSCs exhibit Ca2+ responses to hypo-osmotic stimuli, which are suppressed by TRPV2 inhibitors and TRPV2 deletion, suggesting that MuSCs exhibit TRPV2-dependent mechanical responses. These results establish TRPV2 as a critical regulator of MuSC-mediated muscle remodelling, an important finding that may lead to therapeutic strategies for muscle repair and adaptation. en-copyright= kn-copyright= en-aut-name=ChenYanzhu en-aut-sei=Chen en-aut-mei=Yanzhu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatanosakaKimiaki en-aut-sei=Katanosaka en-aut-mei=Kimiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShibuyaMakoto en-aut-sei=Shibuya en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DongYubing en-aut-sei=Dong en-aut-mei=Yubing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhangLidan en-aut-sei=Zhang en-aut-mei=Lidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KanagawaMotoi en-aut-sei=Kanagawa en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukadaSo-ichiro en-aut-sei=Fukada en-aut-mei=So-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatanosakaYuki en-aut-sei=Katanosaka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka kn-affil= affil-num=6 en-affil=Department of Cell Biology and Molecular Medicine, Ehime University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Laboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka kn-affil= affil-num=8 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=10 article-no= start-page=e70269 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=D3 lymph node dissection in colon cancer patients aged 90?years and over: Is it justified? A multi]institutional retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aim: The oncological benefit of D3 lymph node dissection (D3 LND) for colon cancer in patients aged ?90?years remains unclear. This study aimed to evaluate the impact of D3 LND on outcomes in this specific, vulnerable population.
Method: This retrospective cohort study evaluated 166 patients aged ?90?years with pathological Stages II?III colon cancer undergoing non-D3 or D3 LND from a multicentre database (2011?2022). Postoperative complications, overall survival and cancer-specific survival were compared between LND groups using propensity score-weighted analyses.
Results: D3 LND group had significantly more females and laparoscopic procedures. Operation time was longer, and blood loss was lower in the D3 LND group. Postoperative complications and severe complications were significantly fewer, and postoperative hospital stay was shorter in the D3 LND group. The number of harvested lymph nodes and distal margin was significantly higher in the D3 group. While unadjusted analysis showed better overall survival with D3 LND (p? Conclusion: In nonagenarian colon cancer patients, D3 LND is safe and feasible without increasing complications, but lacks survival benefit. Careful consideration is warranted, and high-quality D2 LND must be consistently ensured when limited surgery is chosen. en-copyright= kn-copyright= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakanagaSatoe en-aut-sei=Takanaga en-aut-mei=Satoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InadaRyo en-aut-sei=Inada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToshimaToshiaki en-aut-sei=Toshima en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtaniTsuyoshi en-aut-sei=Ohtani en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaRyosuke en-aut-sei=Yoshida en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Setouchi Colorectal Neoplasm Registration study group collaborators en-aut-sei=Setouchi Colorectal Neoplasm Registration study group collaborators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Medical Development Field, Okayama University kn-affil= affil-num=5 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Surgery, Saiseikai Okayama Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil= kn-affil= en-keyword=colon cancer kn-keyword=colon cancer en-keyword=lymph node dissection kn-keyword=lymph node dissection en-keyword=nonagenarian kn-keyword=nonagenarian en-keyword=postoperative complication kn-keyword=postoperative complication en-keyword=survival benefit kn-keyword=survival benefit END start-ver=1.4 cd-journal=joma no-vol=411 cd-vols= no-issue=1 article-no= start-page=21 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surgical outcomes and patient selection in nonagenarians with colon cancer: a comparative multi-institutional study of laparoscopic and open approaches en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The appropriate surgical approach for colon cancer (CC) in nonagenarian patients remains a subject of clinical debate. This study aimed to compare the short-term outcomes of laparoscopic (Lap) versus open (Open) surgery in patients aged???90 years with resectable colon cancer.
Methods This multi-institutional retrospective cohort study included oldest-old patientswith pathological Stage II/III CC who underwent elective surgery at 15 hospitals between 2011 and 2022. Patients with rectal cancer, Stage 0/I/IV disease, or emergency surgery were excluded. To address selection bias, inverse-probability-weighted regression adjustment and stabilized inverse probability of treatment weighting (sIPTW) were applied. The primary outcome was postoperative complications; secondary outcomes included overall survival (OS).
Results Median age was 92 years in both groups. Before adjustment, the Lap group had a higher proportion of female patients (p?=?0.038) and lower ASA scores (p?=?0.01). Laparoscopic surgery was associated with a significantly longer operative time (220 vs. 171 min, p?=?0.046) but less intraoperative blood loss (10 vs. 78 mL, p? Conclusion Both laparoscopic and open surgery are feasible options for selected nonagenarians with colon cancer. Laparoscopic surgery may offer benefits in terms of reduced blood loss and shorter hospitalization, despite longer operative times. Careful patient selection considering frailty and comorbidities is essential in determining the most appropriate surgical approach. en-copyright= kn-copyright= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei 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=TakanagaSatoe en-aut-sei=Takanaga en-aut-mei=Satoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InadaRyo en-aut-sei=Inada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToshimaToshiaki en-aut-sei=Toshima en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhtaniTsuyoshi en-aut-sei=Ohtani en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaRyosuke en-aut-sei=Yoshida en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HoriNaoto en-aut-sei=Hori en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShigemitsuKaoru en-aut-sei=Shigemitsu en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoSumiharu en-aut-sei=Yamamoto en-aut-mei=Sumiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KubotaTetsushi en-aut-sei=Kubota en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkanoYuka en-aut-sei=Okano en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NobuhisaTetsuji en-aut-sei=Nobuhisa en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TaniguchiFumitaka en-aut-sei=Taniguchi en-aut-mei=Fumitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IshikawaWataru en-aut-sei=Ishikawa en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsudaTatsuo en-aut-sei=Matsuda en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UmeokaTatsuo en-aut-sei=Umeoka en-aut-mei=Tatsuo 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= en-aut-name=Setouchi Colorectal Neoplasm Registration study group collaborators en-aut-sei=Setouchi Colorectal Neoplasm Registration study group collaborators en-aut-mei= 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=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Saiseikai Okayama Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Tottori Municipal Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, Tsuyama Chuo Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Okayama City Hospital kn-affil= affil-num=12 en-affil=Department of Surgery, Kobe Red Cross Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, Onomichi City Hospital kn-affil= affil-num=14 en-affil=Department of Surgery, Himeji Red Cross Hospital kn-affil= affil-num=15 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=16 en-affil=Department of Surgery, Fukuyama City Hospital kn-affil= affil-num=17 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=18 en-affil=Department of Surgery, Matsuyama City Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=Oldest-old patients kn-keyword=Oldest-old patients en-keyword=Colon cancer kn-keyword=Colon cancer en-keyword=Laparoscopic surgery kn-keyword=Laparoscopic surgery en-keyword=Surgical outcome kn-keyword=Surgical outcome en-keyword=Overall survival kn-keyword=Overall survival END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=3303 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260113 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative efficacy of immune checkpoint inhibitor combination therapies by metastatic site in metastatic renal cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Few studies have investigated the efficacy of immuno-oncology (IO) combinations at different metastatic sites in renal cell carcinoma (RCC). We evaluated the differential efficacy of IO?IO and IO?tyrosine kinase inhibitor (TKI) combinations by metastatic site in metastatic RCC (mRCC). This retrospective multicenter study by the JK-FOOT Study Group included 579 patients with intermediate- or poor-risk mRCC (per International Metastatic RCC Database Consortium criteria) treated with first-line IO combinations between September 2018 and December 2024. Metastatic sites were lymph nodes, lungs, bones, liver, brain, and others. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoint was objective response rate. Efficacy was compared between IO?IO and IO?TKI for each site. For lymph node (n = 36), lung (n = 132), or brain (n = 16) metastases, OS or PFS was not significantly different between IO?IO and IO?TKI. In bone metastases (n = 80), OS tended to favor IO?TKI (P = 0.053). In liver metastases (n = 22), OS was significantly longer with IO?TKI (P = 0.011). IO?TKI may be a more appropriate first-line option than IO?IO for mRCC with bone or liver metastases, while efficacy is similar for other sites. en-copyright= kn-copyright= en-aut-name=ToyodaShingo en-aut-sei=Toyoda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InokiLan en-aut-sei=Inoki en-aut-mei=Lan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HashimotoMamoru en-aut-sei=Hashimoto en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NukayaTakuhisa en-aut-sei=Nukaya en-aut-mei=Takuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsujinoTakuya en-aut-sei=Tsujino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KomuraKazumasa en-aut-sei=Komura en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=InamotoTeruo en-aut-sei=Inamoto en-aut-mei=Teruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=AzumaHaruhito en-aut-sei=Azuma en-aut-mei=Haruhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FujitaKazutoshi en-aut-sei=Fujita en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=JK-FOOT study group en-aut-sei=JK-FOOT study group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Urology, Faculty of Medicine, Kindai University kn-affil= affil-num=2 en-affil=Department of Urology, Faculty of Medicine, Kindai University kn-affil= affil-num=3 en-affil=Department of Urology, Faculty of Medicine, Kindai University kn-affil= affil-num=4 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=8 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=13 en-affil=Department of Urology, Kawasaki University School of Medicine kn-affil= affil-num=14 en-affil=Department of Urology, Fujita-Health University School of Medicine kn-affil= affil-num=15 en-affil=Department of Urology, Hamamatsu University School of Medicine kn-affil= affil-num=16 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=17 en-affil=Department of Urology, Faculty of Medicine, Kindai University kn-affil= affil-num=18 en-affil= kn-affil= en-keyword=Metastatic renal cell carcinoma kn-keyword=Metastatic renal cell carcinoma en-keyword=Bone metastasis kn-keyword=Bone metastasis en-keyword=liver metastasis kn-keyword=liver metastasis en-keyword=Immuno-oncology kn-keyword=Immuno-oncology END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=RP99825 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250618 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Stimulatory and inhibitory G-protein signaling relays drive cAMP accumulation for timely metamorphosis in the chordate Ciona en-subtitle= kn-subtitle= en-abstract= kn-abstract=Larvae of the ascidian Ciona initiate metamorphosis tens of minutes after adhesion to a substratum via their adhesive organ. The gap between adhesion and metamorphosis initiation is suggested to ensure the rigidity of adhesion, allowing Ciona to maintain settlement after losing locomotive activity through metamorphosis. The mechanism producing the gap is unknown. Here, by combining gene functional analyses, pharmacological analyses, and live imaging, we propose that the gap represents the time required for sufficient cyclic adenosine monophosphate (cAMP) accumulation to trigger metamorphosis. Not only the Gs pathway but also the Gi and Gq pathways are involved in the initiation of metamorphosis in the downstream signaling cascade of the neurotransmitter GABA, the known initiator of Ciona metamorphosis. The mutual crosstalk of stimulatory and inhibitory G-proteins functions as the accelerator and brake for cAMP production, ensuring the faithful initiation of metamorphosis at an appropriate time and in the right situation. en-copyright= kn-copyright= en-aut-name=HozumiAkiko en-aut-sei=Hozumi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TotsukaNozomu M en-aut-sei=Totsuka en-aut-mei=Nozomu M kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoderaArata en-aut-sei=Onodera en-aut-mei=Arata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangYanbin en-aut-sei=Wang en-aut-mei=Yanbin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamadaMayuko en-aut-sei=Hamada en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiraishiAkira en-aut-sei=Shiraishi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatakeHonoo en-aut-sei=Satake en-aut-mei=Honoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HorieTakeo en-aut-sei=Horie en-aut-mei=Takeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HottaKohji en-aut-sei=Hotta en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SasakuraYasunori en-aut-sei=Sasakura en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Shimoda Marine Research Center, University of Tsukuba kn-affil= affil-num=2 en-affil=Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University kn-affil= affil-num=3 en-affil=Shimoda Marine Research Center, University of Tsukuba kn-affil= affil-num=4 en-affil=Shimoda Marine Research Center, University of Tsukuba kn-affil= affil-num=5 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=6 en-affil=Bioorganic Research Institute, Suntory Foundation for Life Sciences kn-affil= affil-num=7 en-affil=Bioorganic Research Institute, Suntory Foundation for Life Sciences kn-affil= affil-num=8 en-affil=Laboratory for Single-cell Neurobiology, Graduate School of Frontier Biosciences, Osaka University kn-affil= affil-num=9 en-affil=Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University kn-affil= affil-num=10 en-affil=Shimoda Marine Research Center, University of Tsukuba kn-affil= END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=1 article-no= start-page=16 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Compound heterozygosity of a novel missense variant and exonic deletion in hypomyelinating leukodystrophy 15 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypomyelinating leukodystrophy 15 (HLD15) results from biallelic pathogenic variants in EPRS1, but exonic deletions have not been reported. We describe a 40-year-old woman with mild intellectual disability, ataxia, dystonia, and MRI showing hypomyelination. Whole-exome sequencing identified a heterozygous missense variant in the prolyl-tRNA synthetase domain of EPRS1 (c.3430 C?>?G; p.Leu1144Val, NM_004446.3), without second variant. Whole-genome sequencing revealed a heterozygous 220-bp deletion spanning exon 15 (c.1743-30_1932del), and segregation analysis confirmed compound heterozygosity. RT-PCR from lymphoblastoid cells demonstrated exon-15 skipping leading to a frameshift (p.Asn582Serfs*10) and nonsense-mediated decay, leaving predominant expression of the paternally inherited missense allele. These findings support loss-of-function for the deletion and classify c.3430 C?>?G as likely pathogenic under ACMG/AMP criteria (PM1, PM2, PM3, PP3). This case represents the first exonic deletion reported in EPRS1. The relatively mild, adult-onset phenotype broadens both mutational and clinical spectra of HLD15 and highlights the importance of structural-variant anal en-copyright= kn-copyright= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OrimoKenta en-aut-sei=Orimo en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UedaKunihiro en-aut-sei=Ueda en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SekiTomonari en-aut-sei=Seki en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiioYasushi en-aut-sei=Shiio en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=MoriHarushi en-aut-sei=Mori en-aut-mei=Harushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology kn-affil= affil-num=5 en-affil=Department of Neurology, Tokyo Teishin Hospital kn-affil= affil-num=6 en-affil=Department of Neurology, Tokyo Teishin Hospital kn-affil= affil-num=7 en-affil=Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Radiology, School of Medicine, Jichi Medical University, kn-affil= affil-num=10 en-affil=Institute of Medical Genomics, International University of Health and Welfare kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of Neurology kn-affil= en-keyword=Hypomyelinating leukodystrophy kn-keyword=Hypomyelinating leukodystrophy en-keyword=EPRS1 kn-keyword=EPRS1 en-keyword=Structural variant kn-keyword=Structural variant en-keyword=Exon deletion kn-keyword=Exon deletion en-keyword=Nonsense?mediated decay kn-keyword=Nonsense?mediated decay en-keyword=Whole?genome sequencing kn-keyword=Whole?genome sequencing END start-ver=1.4 cd-journal=joma no-vol=414 cd-vols= no-issue= article-no= start-page=578885 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=Immuno-deficient features of thymoma-associated myasthenia gravis patients with hypogammaglobulinemia: A condition comparable to Good's syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Good's syndrome (GS) is a rare immunodeficiency disorder associated with thymoma, characterized by hypogammaglobulinemia and recurrent infections; however, its clinical significance in thymoma-associated myasthenia gravis (TAMG) remains unclear. We retrospectively reviewed 30 patients with TAMG admitted to our center between January 2010 and March 2022. We defined GS-like immunodeficiency as serum IgG below the institutional cutoff of 861 mg/dL and a history of two or more infections requiring antimicrobial treatment; 11 patients (36.7%) met this definition. Compared with the remaining patients, the GS-like group had higher incidences of malignancy (45.5% vs. 5.3%, p = 0.016) and autoimmune diseases other than MG (36.4% vs. 5.3%, p = 0.047), lower peripheral lymphocyte counts (median 1100/ƒÊL vs. 2200/ƒÊL, p = 0.0051), and more frequent airflow obstruction defined by one second to forced vital capacity ratio of less than 70% (60.0% vs. 5.3%, p = 0.0026). Five deaths occurred in the GS-like group, and none in the other; median survival from the first antimicrobial-treated infection was 5.0 years. These findings imply that TAMG patients with GS-like immunodeficiency have a worse prognosis, underscoring the need for close monitoring and timely adjustments of MG management. (189 words). en-copyright= kn-copyright= en-aut-name=NakashimaSaki en-aut-sei=Nakashima en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakuishiKaori en-aut-sei=Sakuishi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraManato en-aut-sei=Hara en-aut-mei=Manato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawasakiReiko en-aut-sei=Kawasaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakumotoToshiyuki en-aut-sei=Kakumoto en-aut-mei=Toshiyuki 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=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, the University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Teikyo University Chiba Medical Center kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, the University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, the University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, the University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, the University of Tokyo kn-affil= en-keyword=Good's syndrome kn-keyword=Good's syndrome en-keyword=Thymoma-associated myasthenia gravis kn-keyword=Thymoma-associated myasthenia gravis en-keyword=Hypogammaglobulinemia kn-keyword=Hypogammaglobulinemia en-keyword=Immunodeficiency kn-keyword=Immunodeficiency en-keyword=Prognosis kn-keyword=Prognosis END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=50 article-no= start-page=e06926 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collagen Signaling via DDR1 Exacerbates Barriers to Macromolecular Drug Delivery in a 3D Model of Pancreatic Cancer Fibrosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fibrosis is a significant barrier to drug delivery in pancreatic ductal adenocarcinoma (PDAC) and contributes to its dismal prognosis. Pancreatic stellate cells (PSCs) drive fibrosis by excessively secreting extracellular matrix proteins such as collagen I. Collagen I is thought to physically obstruct the delivery of macromolecules, such as albumin, antibodies, and nanomedicines. Apart from its structural role, collagen signals through dedicated cell surface receptors, such as the discoidin domain receptors (DDR) 1/2. However, whether and how collagen signaling contributes to fibrotic barrier generation remains uncharacterized. Here, a 3D culture model of PDAC fibrosis constructed from patient PSCs is used to assess the contribution of DDR1/2-mediated collagen signaling. DDR1/2 inhibition diminishes collagen I expression in PSCs to enhance macromolecular delivery. Moreover, MEK inhibitors exacerbate the fibrotic barrier by up-regulating collagen I, an effect reversed by inhibiting DDR1/2. Through isoform-specific targeting, inhibiting DDR1, but not DDR2, is shown to be effective. Downstream of DDR, the involvement of the PI3K/AKT/mTOR pathway is demonstrated, particularly alternative mTOR complexes involving MEAK7 and GIT1. Altogether, the results show in vitro that DDR1-mediated collagen signaling exacerbates the fibrotic barrier and may be targeted to enhance macromolecular drug delivery in PDAC. en-copyright= kn-copyright= en-aut-name=OhiraMayu en-aut-sei=Ohira en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitamuraMoe en-aut-sei=Kitamura en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IwasakiHiroyo en-aut-sei=Iwasaki en-aut-mei=Hiroyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Ohta]OkanoHaruko en-aut-sei=Ohta]Okano en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiiHiyori en-aut-sei=Tsujii en-aut-mei=Hiyori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraReika en-aut-sei=Nakamura en-aut-mei=Reika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakazawaTakuya en-aut-sei=Nakazawa en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiguchiAkihiro en-aut-sei=Nishiguchi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoMasaya en-aut-sei=Yamamoto en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OsadaKensuke en-aut-sei=Osada en-aut-mei=Kensuke 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=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=KanoMitsunobu R. en-aut-sei=Kano en-aut-mei=Mitsunobu R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Biomaterials Field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science kn-affil= affil-num=9 en-affil=Department of Materials Processing, Graduate School of Engineering, Tohoku University kn-affil= affil-num=10 en-affil=Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Sciences and Technology (QST) kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=13 en-affil=Division of Gastroenterology, Graduate School of Medicine, Tohoku University kn-affil= affil-num=14 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=15 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=collagen kn-keyword=collagen en-keyword=fibrosis kn-keyword=fibrosis en-keyword=nanomedicine kn-keyword=nanomedicine en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=pancreatic stellate cell kn-keyword=pancreatic stellate cell 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 Fisherfs 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? 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 Childrenfs Hospital kn-affil= affil-num=7 en-affil=Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Childrenfs 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 Childrenfs 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 Childrenfs 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=8 cd-vols= no-issue=11 article-no= start-page=e2543107 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trastuzumab Deruxtecan for ERBB2-Mutant Metastatic Non?Small Cell Lung Cancer With or Without Brain Metastases: A Secondary Analysis of Randomized Clinical Trials en-subtitle= kn-subtitle= en-abstract= kn-abstract=Importance Brain metastases reduce overall survival rates of patients with non?small cell lung cancer (NSCLC); patients with epidermal growth factor receptor 2 (ERBB2 [formerly HER2])?mutant NSCLC are more likely to have baseline brain metastases. Trastuzumab deruxtecan (T-DXd) is an approved ERBB2-directed treatment for previously treated unresectable or metastatic ERBB2-mutant NSCLC.
Objective To assess the clinical effectiveness and safety of T-DXd 5.4 mg/kg and 6.4 mg/kg doses in patients with previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases.
Design, Setting, and Participants This post hoc secondary analysis pooled patients from the DESTINY-Lung01 (data cutoff date: December 3, 2021) and DESTINY-Lung02 (data cutoff date: December 23, 2022) clinical trials by T-DXd dose (5.4 mg/kg and 6.4 mg/kg). DESTINY-Lung01 was a multicenter, open-label, 2-cohort, nonrandomized phase 2 study, while DESTINY-Lung02 was a dose-blinded, multicenter, 2-cohort, randomized phase 2 study. Participants had a previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases at baseline. All statistical analyses were performed from April 2023 to October 2024.
Intervention Patients received a T-DXd dose of either 5.4 mg/kg or 6.4 mg/kg intravenously every 3 weeks.
Main Outcome and Measure Systemic and intracranial effectiveness by blinded independent central review using RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1, sites of progression, and safety.
Results This analysis included 102 patients in the T-DXd 5.4-mg/kg dose group (65 females [64%]; median [range] age, 57.5 [37.0-83.0] years and 59.5 [30.0-79.0] years in patients with and without brain metastases, respectively) and 141 patients in the T-DXd 6.4-mg/kg dose group (94 females [67%]; median [range] age, 62.5 [29.0-88.0] years and 59.0 [27.0-83.0] years in patients with and without brain metastases, respectively). In each group, 31% (32 of 102) and 38% (54 of 141) of patients, respectively, had baseline brain metastases and 53% (17 of 32) and 44% (24 of 54), respectively, received prior brain metastasis treatment. In patients with and without brain metastases, systemic confirmed objective response rates (ORRs) were 47% (15 of 32; 95% CI, 29%-65%) and 50% (35 of 70; 95% CI, 38%-62%), respectively, with the T-DXd 5.4-mg/kg dose, and 50% (27 of 54; 95% CI, 36%-64%) and 59% (51 of 87; 95% CI, 48%-69%) with the T-DXd 6.4-mg/kg dose. Median progression-free survival was 7.1 (95% CI, 5.5-9.7) months in the T-DXd 5.4-mg/kg dose group and 7.1 (95% CI, 4.5-9.6) months in the T-DXd 6.4-mg/kg dose group of patients with baseline brain metastases. Among patients with measurable baseline brain metastases, intracranial confirmed ORRs were 50% (7 of 14; 95% CI, 23%-77%) with the T-DXd 5.4-mg/kg dose and 30% (9 of 30; 95% CI, 15%-49%) with the T-DXd 6.4-mg/kg dose. At both doses, the safety profile of T-DXd was generally manageable, regardless of baseline brain metastases, favoring the T-DXd 5.4 mg/kg dose.
Conclusions and Relevance In this secondary analysis, T-DXd at the approved dose of 5.4 mg/kg showed antitumor activity in patients with previously treated ERBB2-mutant metastatic NSCLC with or without brain metastases. This finding supports T-DXd 5.4 mg/kg use in this population. en-copyright= kn-copyright= en-aut-name=J?nnePasi A. en-aut-sei=J?nne en-aut-mei=Pasi A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PlanchardDavid en-aut-sei=Planchard en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GotoKoichi en-aut-sei=Goto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SmitEgbert F. en-aut-sei=Smit en-aut-mei=Egbert F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=de LangenAdrianus Johannes en-aut-sei=de Langen en-aut-mei=Adrianus Johannes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=P?rolMaurice en-aut-sei=P?rol en-aut-mei=Maurice kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=NakagawaKazuhiko en-aut-sei=Nakagawa en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShimizuJunichi en-aut-sei=Shimizu en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NagasakaMisako en-aut-sei=Nagasaka en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=PereiraKaline en-aut-sei=Pereira en-aut-mei=Kaline kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TaguchiAyumi en-aut-sei=Taguchi en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AliAhmed en-aut-sei=Ali en-aut-mei=Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KarnoubMaha en-aut-sei=Karnoub en-aut-mei=Maha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YonemochiRie en-aut-sei=Yonemochi en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=LeungDavid en-aut-sei=Leung en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=LiBob T. en-aut-sei=Li en-aut-mei=Bob T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Thoracic Cancer Group, Gustave Roussy, Medical Oncology kn-affil= affil-num=3 en-affil=Department of Thoracic Oncology, Nation Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Department of Pulmonary Diseases, Leiden University Medical Center kn-affil= affil-num=5 en-affil=Department of Thoracic Oncology, Netherlands Cancer Institute kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=7 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Medical Oncology, Centre L?on B?rard kn-affil= affil-num=10 en-affil=Department of Medical Oncology, Vall dfHebron University and Vall dfHebron Institute of Oncology 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 Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=13 en-affil=Department of Thoracic Oncology, Aichi Cancer Center kn-affil= affil-num=14 en-affil=Division of Hematology-Oncology, Department of Medicine, University of California Irvine kn-affil= affil-num=15 en-affil=Daiichi Sankyo Inc kn-affil= affil-num=16 en-affil=Daiichi Sankyo Co Ltd kn-affil= affil-num=17 en-affil=Daiichi Sankyo Europe GmbH kn-affil= affil-num=18 en-affil=Daiichi Sankyo Inc kn-affil= affil-num=19 en-affil=Daiichi Sankyo Inc kn-affil= affil-num=20 en-affil=Daiichi Sankyo Inc kn-affil= affil-num=21 en-affil=Thoracic Oncology and Early Drug Development Service, Global Research Program, Memorial Sloan Kettering Cancer Center kn-affil= END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=12 article-no= start-page=1814 end-page=1828 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02?A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated HER2 (ERBB2) mutant (HER2m) metastatic NSCLC (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes.
Methods: DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary end point was confirmed objective response rate by blinded independent central review.
Results: As of August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1?Q3) was 15.8 (8.2?20.7) months and 16.5 (9.4?20.8) months, respectively. Confirmed objective response rate (95% confidence interval) was 50.0% (51/102; 39.9%?60.1%) and 56.0% (28/50; 41.3%?70.0%), respectively. Safety profile was acceptable and generally manageable. Accordingly, median treatment duration (Q1?Q3) was 7.7 (3.7?14.4) months and 8.3 (2.8?13.1) months; drug-related grade 3 or higher treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1 or 2 with one grade 5 in each arm. Health-related quality of life was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on health-related quality of life observed at either dose.
Conclusions: T-DXd demonstrated strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4-mg/kg dose demonstrated a more favorable benefit-risk profile, including lower adjudicated drug-related interstitial lung disease incidence.
ClinicalTrials.gov identifier: NCT04644237 en-copyright= kn-copyright= en-aut-name=J?nnePasi A. en-aut-sei=J?nne en-aut-mei=Pasi A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimSang-We en-aut-sei=Kim en-aut-mei=Sang-We kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PlanchardDavid en-aut-sei=Planchard en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AhnMyung-Ju en-aut-sei=Ahn en-aut-mei=Myung-Ju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SmitEgbert en-aut-sei=Smit en-aut-mei=Egbert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Johannes de LangenAdrianus en-aut-sei=Johannes de Langen en-aut-mei=Adrianus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=P?rolMaurice en-aut-sei=P?rol en-aut-mei=Maurice kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Pons-TostivintElvire en-aut-sei=Pons-Tostivint en-aut-mei=Elvire kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NovelloSilvia en-aut-sei=Novello en-aut-mei=Silvia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=ShimizuJunichi en-aut-sei=Shimizu en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KimDong-Wan en-aut-sei=Kim en-aut-mei=Dong-Wan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=PereiraKaline en-aut-sei=Pereira en-aut-mei=Kaline kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ChengFu-Chih en-aut-sei=Cheng en-aut-mei=Fu-Chih kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TaguchiAyumi en-aut-sei=Taguchi en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ChengYingkai en-aut-sei=Cheng en-aut-mei=Yingkai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=DuntonKyle en-aut-sei=Dunton en-aut-mei=Kyle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AliAhmed en-aut-sei=Ali en-aut-mei=Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=GotoKoichi en-aut-sei=Goto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, National Cancer Central Hospital kn-affil= affil-num=3 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Oncology Department, Asan Medical Center, Seoul, and University of Ulsan College of Medicine, Ulsan kn-affil= affil-num=6 en-affil=Department of Medical Oncology, Thoracic Cancer Group, Gustave Roussy, and Faculty of Medicine, Paris-Saclay University kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Samsung Medical Center Sungkyunkwan, and University School of Medicine kn-affil= affil-num=8 en-affil=Department of Pulmonary Diseases, Leiden University Medical Center kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, Netherlands Cancer Institute kn-affil= affil-num=10 en-affil=Department of Medical Oncology, L?on Berard Centre kn-affil= affil-num=11 en-affil=Centre Hospitalier Universitaire Nantes, Nantes University kn-affil= affil-num=12 en-affil=Department of Oncology, University of Turin, Turin, and Azienda Ospedaliero-Universitaria San Luigi Gonzaga kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Kindai University Hospital kn-affil= affil-num=14 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=15 en-affil=Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital kn-affil= affil-num=16 en-affil=Daiichi Sankyo kn-affil= affil-num=17 en-affil=Daiichi Sankyo kn-affil= affil-num=18 en-affil=Daiichi Sankyo kn-affil= affil-num=19 en-affil=Daiichi Sankyo kn-affil= affil-num=20 en-affil=Daiichi Sankyo UK kn-affil= affil-num=21 en-affil=Daiichi Sankyo Europe GmbH kn-affil= affil-num=22 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East kn-affil= en-keyword=HER2-directed therapy kn-keyword=HER2-directed therapy en-keyword=HER2-mutant kn-keyword=HER2-mutant en-keyword=HER2-targeted kn-keyword=HER2-targeted en-keyword=Non?small cell lung cancer kn-keyword=Non?small cell lung cancer en-keyword=Trastuzumab deruxtecan kn-keyword=Trastuzumab deruxtecan END start-ver=1.4 cd-journal=joma no-vol=88 cd-vols= no-issue=5 article-no= start-page=1003 end-page=1015 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251222 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Claudin-18 expression in gastric type adenocarcinoma and HPV-associated adenocarcinoma of the uterine cervix en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Claudin-18 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43-14A antibody, or about the gene expression of its isoforms in ECAs.
Methods and results: We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high-risk human papillomavirus (HR-HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV-independent adenocarcinomas (gastric type [GAS], n?=?24; non-GAS, n?=?11) and 86 HPV-associated ECAs. We also analysed mRNA expression of the CLDN18.1 (lung type) and CLDN18.2 (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8/24 (33%) GASs, 0/11 (0%) non-GASs and 2/86 (2%) HPV-associated ECAs, with positivity defined as staining in ?75% of tumour cells, as in gastric cancer. When a 5% cut-off was used, CLDN18 positivity was detected in 22/24 (92%) GASs, 0/11 (0%) non-GASs and 6/86 (7%) HPV-associated ECAs; CLDN18 expression was thus significantly associated with GAS histology (P? Conclusions: CLDN18 (43-14A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV-associated ECAs also can be immunoreactive for CLDN18 and express CLDN18.2 mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV-associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16. en-copyright= kn-copyright= en-aut-name=YasutakeNobuko en-aut-sei=Yasutake en-aut-mei=Nobuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokawaYuki en-aut-sei=Yokawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MishimaRiri en-aut-sei=Mishima en-aut-mei=Riri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KomamizuMisato en-aut-sei=Komamizu en-aut-mei=Misato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KugaRyosuke en-aut-sei=Kuga en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=JiromaruRina en-aut-sei=Jiromaru en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawatokoShinichiro en-aut-sei=Kawatoko en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SonodaKenzo en-aut-sei=Sonoda en-aut-mei=Kenzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YahataHideaki en-aut-sei=Yahata en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatoKiyoko en-aut-sei=Kato en-aut-mei=Kiyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OdaYoshinao en-aut-sei=Oda en-aut-mei=Yoshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= affil-num=1 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=2 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University Fukuoka Japan kn-affil= affil-num=6 en-affil=Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=7 en-affil=Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=8 en-affil=Department of Medicine and Clinical Science, Kyushu University Beppu Hospital kn-affil= affil-num=9 en-affil=Department of Gynecology, Kyushu University Beppu Hospital kn-affil= affil-num=10 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=11 en-affil=Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=12 en-affil=Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=13 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University kn-affil= en-keyword=claudin-18 kn-keyword=claudin-18 en-keyword=endocervical adenocarcinoma kn-keyword=endocervical adenocarcinoma en-keyword=gastric type kn-keyword=gastric type en-keyword=human papillomavirus kn-keyword=human papillomavirus en-keyword=p16 kn-keyword=p16 END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page=e87334 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250705 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Challenge of Diagnosing Scirrhous Gastric Cancer by Endoscopic Biopsy: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Scirrhous gastric cancer, also known as linitis plastica, is a rare and aggressive subtype of gastric carcinoma that poses significant diagnostic challenges due to its submucosal infiltration and often normal-appearing mucosa. We report a case involving a 30-year-old Japanese woman who presented with a six-month history of epigastric pain and postprandial vomiting. Initial endoscopic examination revealed erythema and mucosal swelling, with limited antral distensibility and resistance during duodenal intubation. Despite 12 mucosal biopsies, histopathological examination revealed no evidence of malignancy. Given the strong clinical and endoscopic suspicion of scirrhous gastric cancer, additional deep sections and immunohistochemical staining were performed. These revealed scattered signet-ring cell carcinoma and poorly differentiated adenocarcinoma, with positive immunostaining for p53 and Ki67. The patient underwent total gastrectomy, and the diagnosis of scirrhous gastric cancer was confirmed on the resected specimen. This case highlights the importance of a high index of clinical suspicion, close collaboration between endoscopists and pathologists, and the utility of ancillary diagnostic tools, such as immunohistochemistry, in identifying subepithelial gastric malignancies that may be missed on conventional biopsy. en-copyright= kn-copyright= en-aut-name=IkedaYuka en-aut-sei=Ikeda en-aut-mei=Yuka 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=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi 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=IkedaNobumasa en-aut-sei=Ikeda en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Clinic IkedaDepartment of Internal Medicine, Clinic Ikeda kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Clinic Ikeda kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=endoscopic biopsy kn-keyword=endoscopic biopsy en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=immunohistochemistry kn-keyword=immunohistochemistry en-keyword=linitis plastica kn-keyword=linitis plastica en-keyword=scirrhous gastric cancer kn-keyword=scirrhous gastric cancer END start-ver=1.4 cd-journal=joma no-vol=191 cd-vols= no-issue= article-no= start-page=79 end-page=91 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utilizing a Preferred Character as a Stimulus Prompt to Teach Table-Wiping Skills to a Student With Autism Spectrum Disorder en-subtitle= kn-subtitle= en-abstract= kn-abstract=@This study examined the effectiveness of a preferred character as a stimulus prompt in teaching table-wiping skills to a student with intellectual disability and autism spectrum disorder who had pervasive support needs. A multiple-treatments design was utilized to determine if the projected character prompt strategy was the most effective, followed by the character puppet prompt and the marker prompt. Results indicated that the marker prompt strategy and the projected character strategy were equally effective in helping the student to acquire table-wiping skills and more effective than the character puppet prompt strategy. However, the projected character prompt strategy elicited the most positive expressions and the fewest refusal behaviors. In contrast, the marker prompt strategy induced the fewest positive express ions and the most refusa l behaviors. en-copyright= kn-copyright= en-aut-name=MatsushitaYoshimasa en-aut-sei=Matsushita en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtakeYoshihisa en-aut-sei=Ohtake en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=The Joint Graduate School in Science of School Education (Doctorfs Course), Hyogo University of Teacher Education kn-affil= affil-num=2 en-affil=Faculty of Education, Okayama University kn-affil= en-keyword=stimulus prompt kn-keyword=stimulus prompt en-keyword=cleaning kn-keyword=cleaning en-keyword=autism spectrum disorder kn-keyword=autism spectrum disorder en-keyword=intellectual disability kn-keyword=intellectual disability en-keyword=projected character kn-keyword=projected character END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=2 article-no= start-page=284 end-page=293 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=Clinical Characteristics and Spatial Transcriptome Analysis of Non?Small Cell Lung Cancers Exhibiting Early Alectinib Resistance: A Retrospective OLCSG Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Some anaplastic lymphoma kinase (ALK) gene rearrangement?positive lung cancers show early resistance, within 3 months, to alectinib. This study investigated the clinical and molecular characteristics of these patients. We analyzed patients with unresectable stage III/IV disease without indications for radical radiotherapy and recurrent ALK-positive lung cancer who received alectinib as the primary ALK tyrosine kinase inhibitor between 2013 and 2021 at nine hospitals. In total, 103 patients were included. The median age was 65 years; 44 were male and 22 had brain metastases. The median progression-free survival and overall survival (OS) were 28.7 and 80.6 months. Nineteen patients treated for ?3 months and 84 treated for >3 months were categorized into the early resistance and responder groups, respectively. The early resistance group had significantly shorter OS (8.4 months vs. not estimable, P < 0.001) and was significantly more likely to have brain metastases (42% vs. 17%, P = 0.027). They also showed elevated inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR). Univariate analysis identified brain metastases and high NLR as significant predictors of early resistance. Spatial transcriptome analysis and immunohistochemical staining revealed upregulation of annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein involved in inflammation and cancer progression, in the early resistance group. Interleukin 6 stimulation, prompted by elevated inflammatory markers, increased ANXA1 expression and reduced alectinib sensitivity. Knockdown of ANXA1 improved alectinib sensitivity in alectinib-resistant cells. In conclusion, brain metastases and high NLR are associated with early resistance. ANXA1 may play an important role in mediating early resistance. New treatment options for the early resistance group are required. en-copyright= kn-copyright= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KudoKenichiro en-aut-sei=Kudo en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HoritaNaokatsu en-aut-sei=Horita en-aut-mei=Naokatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KayataniHiroe en-aut-sei=Kayatani en-aut-mei=Hiroe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SugimotoKeisuke en-aut-sei=Sugimoto en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology and Medicine, National Hospital Organization, Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Kure Kyosai Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=12 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital kn-affil= affil-num=14 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=sr.2024-0099 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=The Qualification Examination for Specialists and Instructors in the Japanese Society of Neuroendovascular Therapy: History and Current Status en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neuroendovascular therapy is a key treatment for cerebrovascular disorders, driven by advancements in devices and techniques. The Japanese Society for Neuroendovascular Therapy (JSNET) established a certification system in 1997 to ensure operator competence and minimize complications, with the first examination in 2002. JSNET offers 2 main certifications: specialist and instructor. Specialists perform basic procedures, while instructors lead in practice, education, and research. In 2020, the mechanical thrombectomy practitioner qualification was added to promote mechanical thrombectomy. Applicants must have a JSNET membership, relevant certifications, training, and documented experience. The certification process includes rigorous written and practical examinations that now employ non-fluoroscopic models. Certification renewal every 5 years requires conference participation and a continuing education program. Public awareness and integration into stroke center designations have grown. Over 2200 specialists, including more than 500 instructors, have been certified, significantly advancing neuroendovascular therapy in Japan. JSNET aims to continue improving certification and education to maintain high standards. en-copyright= kn-copyright= en-aut-name=YoshimuraShinichi en-aut-sei=Yoshimura en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiuKenji en-aut-sei=Sugiu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirohataMasaru en-aut-sei=Hirohata en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EnomotoYukiko en-aut-sei=Enomoto en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImamuraHirotoshi en-aut-sei=Imamura en-aut-mei=Hirotoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsurutaWataro en-aut-sei=Tsuruta en-aut-mei=Wataro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujinakaToshiyuki en-aut-sei=Fujinaka en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HasegawaHitoshi en-aut-sei=Hasegawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HigashiToshio en-aut-sei=Higashi en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IzumiTakashi en-aut-sei=Izumi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KiyosueHiro en-aut-sei=Kiyosue en-aut-mei=Hiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsumotoYasushi en-aut-sei=Matsumoto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OishiHidenori en-aut-sei=Oishi en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SatowTetsu en-aut-sei=Satow en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaMichihiro en-aut-sei=Tanaka en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TsumotoTomoyuki en-aut-sei=Tsumoto en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamagamiHiroshi en-aut-sei=Yamagami en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IshiiAkira en-aut-sei=Ishii en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MatsumaruYuji en-aut-sei=Matsumaru en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MiyachiShigeru en-aut-sei=Miyachi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Neurosurgery, Hyogo Medical University kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Kurume Medical University kn-affil= affil-num=4 en-affil=Department of Neurosurgery, Gifu University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Neurosurgery, National Cerebral and Cardiovascular Center kn-affil= affil-num=6 en-affil=Department of Endovascular Neurosurgery, Toranomon Hospital kn-affil= affil-num=7 en-affil=Department of Neurosurgery, National Hospital Organization Osaka National Hospital kn-affil= affil-num=8 en-affil=Department of Neurosurgery, Brain Research Institute, Niigata University kn-affil= affil-num=9 en-affil=Department of Neurosurgery, Fukuoka University Chikushi Hospital kn-affil= affil-num=10 en-affil=Department of Neurosurgery, Nagoya University of Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Diagnostic Radiology, Kumamoto University Faculty of Life Sciences kn-affil= affil-num=12 en-affil=Division of Development and Discovery of Interventional Therapy, Tohoku University Hospital kn-affil= affil-num=13 en-affil=Oishi Neurosurgery Clinic, and Department of Neurosurgery, The Jikei University School of Medicine kn-affil= affil-num=14 en-affil=Department of Neurosurgery/Stroke Center, Kindai University Hospital kn-affil= affil-num=15 en-affil=Department of Neurosurgery and Neuroendovascular Surgery, Kameda Neurocenter, Kameda Medical Center kn-affil= affil-num=16 en-affil=Department of Neurosurgery, Showa University Fujigaoka Hospital kn-affil= affil-num=17 en-affil=Division of Stroke Prevention and Treatment, Institute of Medicine, University of Tsukuba kn-affil= affil-num=18 en-affil=Department of Neurosurgery, Juntendo University Faculty of Medicine kn-affil= affil-num=19 en-affil=Department of Neurosurgery, Institute of Medicine, University of Tsukuba kn-affil= affil-num=20 en-affil=Department of Neurological Surgery, Aichi Medical Univeristy kn-affil= en-keyword=neuroendovascular therapy kn-keyword=neuroendovascular therapy en-keyword=specialist certification kn-keyword=specialist certification en-keyword=Japanese Society for Neuroendovascular Therapy (JSNET) kn-keyword=Japanese Society for Neuroendovascular Therapy (JSNET) en-keyword=mechanical thrombectomy kn-keyword=mechanical thrombectomy 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=2026 dt-pub=20260213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distinct associations of blood pressure phenotypes with subclinical cerebrovascular disease and coronary artery calcification in Japanese men en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypertension, encompassing white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH), is an established risk factor for cardiovascular diseases (CVDs), including atherosclerosis. However, among the general population, findings on which target organ is affected by the different phenotypes of hypertension remain unclear. In this community-based observational study of Shiga Epidemiological Study of Subclinical Atherosclerosis, 740 Japanese men underwent brain magnetic resonance imaging to assess the presence of lacunar infarction, white-matter hyperintensities, microbleeds, and intracranial artery stenosis (ICAS) between 2012 and 2015. They also underwent office blood pressure (BP) measurements, home BP monitoring for at least five consecutive days, and coronary artery calcification (CAC) assessments between 2010 and 2014. The final analysis included 686 participants without a history of CVDs. Of the 686 participants, the mean age (?}?SD) was 68.0 (?}?8.3) years, and 39.3% were taking antihypertensive medication. In multivariable-adjusted models, each of WCH, MH, and SH was significantly associated with a higher risk of microbleeds compared to normotension. However, the association of WCH with microbleeds was evident only among those on antihypertensive medication (adjusted odds ratio [OR] 6.75 [95% CI 1.83?24.86]) and absent in those not on such medication (adjusted OR 1.20 [95% CI 0.31?4.73]). SH was associated with lacunar infarction, ICAS, and CAC. Among Japanese men, WCH, MH, SH were associated with subclinical cerebrovascular diseases, whereas only SH was associated with CAC. Moreover, any elevated BP phenotype increased the risk of microbleeds. Our findings suggest that different hypertension phenotypes distinctly affect target organs, particularly the brain and heart. en-copyright= kn-copyright= en-aut-name=BayaraaNomin en-aut-sei=Bayaraa en-aut-mei=Nomin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanoYuichiro en-aut-sei=Yano en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KadotaAya en-aut-sei=Kadota en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AzaharNazar Mohd en-aut-sei=Azahar en-aut-mei=Nazar Mohd kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=PhapTran Ngoc Hoang en-aut-sei=Phap en-aut-mei=Tran Ngoc Hoang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KondoKeiko en-aut-sei=Kondo en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ToriiSayuki en-aut-sei=Torii en-aut-mei=Sayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiyoshiAkira en-aut-sei=Fujiyoshi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhkuboTakayoshi en-aut-sei=Ohkubo en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShiinoAkihiko en-aut-sei=Shiino en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NozakiKazuhiko en-aut-sei=Nozaki en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiuraKatsuyuki en-aut-sei=Miura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=2 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=3 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=4 en-affil= kn-affil= affil-num=5 en-affil=National Institutes of Biomedical Innovation, Health and Nutrition kn-affil= affil-num=6 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=8 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=9 en-affil=Department of Hygiene, School of Medicine, Wakayama Medical University kn-affil= affil-num=10 en-affil=Department of Hygiene and Public Health, Teikyo University School of Medicine kn-affil= affil-num=11 en-affil=Molecular Neuroscience Research Center, Shiga University of Medical Science kn-affil= affil-num=12 en-affil=Department of Neurosurgery, Shiga University of Medical Science kn-affil= affil-num=13 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= en-keyword=Blood pressure phenotypes kn-keyword=Blood pressure phenotypes en-keyword=Morning hypertension kn-keyword=Morning hypertension en-keyword=Home blood pressure kn-keyword=Home blood pressure en-keyword=Subclinical cerebrovascular disease kn-keyword=Subclinical cerebrovascular disease en-keyword=Coronary artery calcification kn-keyword=Coronary artery calcification END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=3 article-no= start-page=179 end-page=187 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis and applications of porous carbonaceous materials with inherited molecular structural features from the precursor molecules en-subtitle= kn-subtitle= en-abstract= kn-abstract=The carbonization of organic crystalline materials, such as metal organic frameworks and covalent organic frameworks, has emerged as a promising approach for producing functional porous carbonaceous materials. However, both the chemically defined long-term ordered structures and the local chemical structures derived from these precursor materials are generally lost, resulting in amorphous carbons. As a result, controlling the molecular-level structure of nanoporous carbons remains a significant challenge. We report a new bottom-up synthesis approach for porous carbons with a molecular-level design, involving the carbonization of well-designed precursor molecules by thermal polymerization. Among the resulting carbons, ordered carbonaceous frameworks, which contain a high-density of regularly aligned single-atomic metal species, have been identified as promising platforms for single-atom catalysts. This approach also enables the synthesis of various three-dimensional porous carbons that reflect the structural features of their precursor molecules. Recent progress in the synthesis and applications of porous carbons derived from molecular precursors is summarized, highlighting their potential for the development of functional materials. en-copyright= kn-copyright= en-aut-name=ChidaKoki en-aut-sei=Chida en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshiTakeharu en-aut-sei=Yoshi en-aut-mei=Takeharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KamiyaKazuhide en-aut-sei=Kamiya en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoRyota en-aut-sei=Sakamoto en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniFumito en-aut-sei=Tani en-aut-mei=Fumito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OgoshiTomoki en-aut-sei=Ogoshi en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiharaHirotomo en-aut-sei=Nishihara en-aut-mei=Hirotomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=2 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Science, Tohoku University kn-affil= affil-num=6 en-affil=Institute for Materials Chemistry and Engineering, Kyushu University kn-affil= affil-num=7 en-affil=Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University kn-affil= affil-num=8 en-affil=Institute of Multidisciplinary Research for Advanced Materials, Tohoku University kn-affil= en-keyword=Ordered carbonaceous frameworks (OCFs) kn-keyword=Ordered carbonaceous frameworks (OCFs) en-keyword=Porous carbon materials kn-keyword=Porous carbon materials en-keyword=Single-atom catalysts (SACs) kn-keyword=Single-atom catalysts (SACs) en-keyword=Catalyst supports kn-keyword=Catalyst supports END start-ver=1.4 cd-journal=joma no-vol=183 cd-vols= no-issue= article-no= start-page=111902 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=Monitoring postharvest water loss in eggplants (Solanum melongena L.) using UV-induced fluorescence imaging and multivariate analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Eggplant (Solanum melongena L.) is susceptible to significant postharvest losses primarily due to water loss during storage, which affects market quality by causing texture and glossiness degradation. We investigated whether UV-induced fluorescence imaging and EEM (Excitation-Emission Matrix) fluorescence spectroscopy can non-destructively monitor WL under four storage regimes (10 ‹C/95 % RH, 20 ‹C/95 % RH, 20 ‹C/75 % RH, 10 ‹C/75 % RH). EEMs exhibited three regions; a 365/420 nm blue emission increased most under warm, low-humidity storage and is consistent with phenolic/lignin-related fluorescence. Side-view fluorescence (FL) images showed progressive blue-white emission and surface textural changes that tracked gravimetric water loss (WL). A PLSR model using combined color and texture features from FL and reflectance (CL) images achieved R2CV = 0.88 (RMSECV = 3.47 %) with only six features. To test a minimal predictor, we fit an Analysis of Covariance (ANCOVA) using Day-1 FL MeanBlue as a covariate and storage category as a factor with Leave One Out Cross-validation (LOOCV); this forecasted cumulative WL with R2LOOCV = 0.92 and MAE = 1.88 %. Importantly, this ANCOVA model using Day-1 blue-band fluorescence as a covariate was predictive only under 20 ‹C/75 % RH; under the other conditions, its contribution was weak. Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) models achieved accuracies of 94.4 % and 85.2 %, respectively, in differentiating storage conditions. These results support low-cost FL imaging as a practical tool to monitor WL and storage stress. en-copyright= kn-copyright= en-aut-name=RotichVincent en-aut-sei=Rotich en-aut-mei=Vincent kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GaoTianqi en-aut-sei=Gao en-aut-mei=Tianqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PrempreePanintorn en-aut-sei=Prempree en-aut-mei=Panintorn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayashiTakahiro en-aut-sei=Hayashi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NambaKazuhiko en-aut-sei=Namba en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MontaMitsuji en-aut-sei=Monta en-aut-mei=Mitsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimotoMotomi en-aut-sei=Nishimoto en-aut-mei=Motomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoNaoshi en-aut-sei=Kondo en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=2 en-affil=Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=3 en-affil=Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=4 en-affil=Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Technology and Innovation Center, Daikin Industries, Ltd. kn-affil= affil-num=8 en-affil=Laboratory of Biosensing Engineering, Graduate School of Agriculture, Kyoto University kn-affil= en-keyword=Eggplant kn-keyword=Eggplant en-keyword=Fluorescence spectroscopy kn-keyword=Fluorescence spectroscopy en-keyword=UV-Induced imaging kn-keyword=UV-Induced imaging en-keyword=Water loss kn-keyword=Water loss en-keyword=Postharvest quality kn-keyword=Postharvest quality en-keyword=Non-destructive assessment kn-keyword=Non-destructive assessment END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=pgaf393 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251222 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Chloroplast heat shock protein cpHsc70-1 interacts with thylakoid membrane remodeling protein VIPP1 C-terminal tail and controls VIPP1 oligomer assembly en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oxygenic photosynthetic organisms depend on the thylakoid membranes (TMs) for light-driven energy conversion. Recent studies on TM homeostasis (thylakostasis) have highlighted the essential role of the TM remodeling protein vesicle-inducing protein in plastid 1 (VIPP1). As a member of the endosomal sorting complexes required for transport-III (ESCRT-III)/phage shock protein A (PspA)/VIPP1 superfamily, VIPP1 forms large ring- and filament-like homo-oligomeric structures that exhibit a membrane remodeling activity. The oligomerization status was proposed to be modulated by the intrinsically disordered C-terminal tail (Vc), whereas its functional role remained unclear. Notably, this Vc region is conserved not only in photosynthetic VIPP1 but also in the PspA proteins of extremophilic species, implicating its role in membrane stress responses. To investigate the role of the Vc region in VIPP1 assembly, we performed coimmunoprecipitation assays in Arabidopsis chloroplasts and identified chloroplast-localized HSP70 proteins (cpHsc70) as major interactors. Among the two isoforms, cpHsc70-1 was found to be specifically required for modulating VIPP1 oligomeric assembly and dynamics in response to heat stress. Genetic analyses revealed that cpHsc70-1 facilitates the disassembly of VIPP1 oligomers, similarly to Vps4 ATPase in ESCRT-III; loss of either the Vc region or cpHsc70-1-impaired VIPP1 disassembly, resulting in more static oligomeric structures. Furthermore, cpHsc70-1 exhibited a broader role in chloroplast proteostasis, as the cphsc70-1 mutant showed impaired accumulation of green fluorescent protein (GFP)-fusion proteins. Together, our findings uncover a crucial crosstalk between proteostasis and thylakostasis in chloroplasts, coordinated by cpHsc70-1 and VIPP1 in response to membrane stress. en-copyright= kn-copyright= en-aut-name=LiDi en-aut-sei=Li en-aut-mei=Di kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GachieSarah Wanjiru en-aut-sei=Gachie en-aut-mei=Sarah Wanjiru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OzawaShin-ichiro en-aut-sei=Ozawa en-aut-mei=Shin-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ScholzMartin en-aut-sei=Scholz en-aut-mei=Martin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HipplerMichael en-aut-sei=Hippler en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakamotoWataru en-aut-sei=Sakamoto en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Biology and Biotechnology, University of M?nster kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=chloroplast kn-keyword=chloroplast en-keyword=heat shock protein kn-keyword=heat shock protein en-keyword=photosynthesis kn-keyword=photosynthesis en-keyword=thylakoid membrane remodeling kn-keyword=thylakoid membrane remodeling END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=2 article-no= start-page=444 end-page=451 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=Interactive Effects of Maximum Daytime and Minimum Nighttime Temperatures on Spinach Growth and Physiological Characteristics en-subtitle= kn-subtitle= en-abstract= kn-abstract=High temperatures restrict spinach growth, and the plantfs growth and physiological responses to heat remain poorly understood. It remains unclear whether high daytime or elevated nighttime temperatures have a more negative impact on spinach growth. In addition, the interaction effect of maximum daytime and minimum nighttime temperatures on spinach growth remains unknown. This study was conducted to address these issues. Spinach was grown in controlled environments under four temperature treatments: 30 and 20 ‹C (T30/20), 30 and 25 ‹C (T30/25), 35 and 20 ‹C (T35/20), and 35 and 25 ‹C (T35/25). These treatments represent the maximum daytime temperature and minimum nighttime temperature, respectively, and were maintained for 45 days. Plant growth characteristics were monitored, and the physiological responses to temperature regimes were assessed. The results show that compared with T30/20, dry matter production decreased by 15.4% with increased nighttime temperature (T30/25), decreased by 42.3% with increased daytime temperature (T35/20), and decreased by 57.7% when both daytime and nighttime temperatures were increased (T35/25). However, there was no statistically significant interaction effect (P > 0.05) between daytime maximum and nighttime minimum temperatures on plant biomass production variables. In comparison with T30/20, the T35/25 treatment increased significantly plant stomatal conductance, stomatal apertures, transpiration rate, and leaf temperature during heat waves. The T35/25 treatment also decreased the quantum efficiency in light compared with the other treatments. Plant biomass production did not improve with the T35/20 and T35/25 treatments, likely as a result of a decoupling of photosynthesis and stomatal conductance during heat waves. Overall, these results reveal that maximum daytime and minimum nighttime temperatures exert additive effects on spinach growth. en-copyright= kn-copyright= en-aut-name=SambaNethone en-aut-sei=Samba en-aut-mei=Nethone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkasakaHisao en-aut-sei=Akasaka en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasubaKen-ichiro en-aut-sei=Yasuba en-aut-mei=Ken-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoTanjuro en-aut-sei=Goto en-aut-mei=Tanjuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Hikawa-EndoMinori en-aut-sei=Hikawa-Endo en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyamaYoko en-aut-sei=Miyama en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Faculty of Food and Agricultural Sciences, Fukushima University kn-affil= affil-num=2 en-affil=The United Graduate School of Agricultural Sciences, Iwate University, Iwate, 020-8550, Japan; and Iwate Agricultural Research Center, Kenpoku Agricultural Research Institute kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Food and Agricultural Sciences, Fukushima University, Fukushima, 960-1296, Japan; and The United Graduate School of Agricultural Sciences, Iwate University kn-affil= en-keyword=photosynthesis kn-keyword=photosynthesis en-keyword=quantum efficiency kn-keyword=quantum efficiency en-keyword=stomatal aperture kn-keyword=stomatal aperture en-keyword=stomatal conductance kn-keyword=stomatal conductance en-keyword=transpiration kn-keyword=transpiration END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=1 article-no= start-page=146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Safety and feasibility of D3 lymph node dissection in oldest-old patients undergoing colorectal cancer surgery: a multi-institutional, retrospective analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Colorectal cancer (CRC) is a significant health burden, with lymph node dissection (LND) playing a critical role in staging and guiding treatment. However, the optimal extent of LND for the oldest-old population (aged???90 years) remains undefined because of insufficient targeted clinical data. This study aimed to compare the short-term outcomes of D3 versus non-D3 LND in Stage II?III CRC in oldest-old patients.
Methods This retrospective cohort study utilized data from the Setouchi Colorectal Neoplasm Registration database, including 282 oldest-old patients with CRC treated between 2011 and 2022. Patients were stratified into D3 and non-D3 LND groups, with inverse-probability-weighted regression adjustment implemented to address potential confounding factors. Postoperative complications and hospital stays were analyzed using regression models and descriptive statistics.
Results D3 LND resulted in significantly higher lymph node harvests in both Stage II and Stage III patients (p? Conclusions D3 LND can be safely performed in oldest-old patients with CRC without increasing postoperative complications or extending hospital stays. These findings support the feasibility of extensive LND in this age gr en-copyright= kn-copyright= en-aut-name=InadaR. en-aut-sei=Inada en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraishiF. en-aut-sei=Teraishi en-aut-mei=F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiT. en-aut-sei=Mitsuhashi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakanagaS. en-aut-sei=Takanaga en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToshimaT. en-aut-sei=Toshima en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtaniT. en-aut-sei=Ohtani en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaR. en-aut-sei=Yoshida en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HoriN. en-aut-sei=Hori en-aut-mei=N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShigemitsuK. en-aut-sei=Shigemitsu en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoS. en-aut-sei=Yamamoto en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KubotaT. en-aut-sei=Kubota en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkanoY. en-aut-sei=Okano en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NobuhisaT. en-aut-sei=Nobuhisa en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaniguchiF. en-aut-sei=Taniguchi en-aut-mei=F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshikawaW. en-aut-sei=Ishikawa en-aut-mei=W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShojiR. en-aut-sei=Shoji en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsudaT. en-aut-sei=Matsuda en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UmeokaT. en-aut-sei=Umeoka en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraT. en-aut-sei=Fujiwara en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Setouchi Colorectal Neoplasm Registration Study Group Collaborators en-aut-sei=Setouchi Colorectal Neoplasm Registration Study Group Collaborators en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Surgery, Kochi Health Sciences Center 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=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Surgery, Saiseikai Okayama Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Tottori Municipal Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Tsuyama Chuo Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, Okayama City Hospital kn-affil= affil-num=11 en-affil=Department of Surgery, Kobe Red Cross Hospital kn-affil= affil-num=12 en-affil=Department of Surgery, Onomichi City Hospital kn-affil= affil-num=13 en-affil=Department of Surgery, Himeji Red Cross Hospital kn-affil= affil-num=14 en-affil=Department of Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=15 en-affil=Department of Surgery, Fukuyama City Hospital 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 Surgery, Matsuda Hospital kn-affil= affil-num=18 en-affil=Department of Surgery, Matsuyama City Hospital kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil= kn-affil= en-keyword=Lymph node dissection kn-keyword=Lymph node dissection en-keyword=Colorectal cancer kn-keyword=Colorectal cancer en-keyword=Oldest-old patients kn-keyword=Oldest-old patients en-keyword=Postoperative complication kn-keyword=Postoperative complication END start-ver=1.4 cd-journal=joma no-vol=95 cd-vols= no-issue=1 article-no= start-page=10 end-page=20 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of Fruit Development, Ripening, and Transcriptome Dynamics in Taiwanese and Japanese Cultivars of Japanese Apricot (Prunus mume Sieb. et Zucc.) en-subtitle= kn-subtitle= en-abstract= kn-abstract=In this study, we compared changes in traits associated with fruit development and ripening in Taiwanese and Japanese cultivars of Japanese apricot (Prunus mume Sieb. et Zucc.). We also analyzed transcriptome profiles to comprehensively examine different fruit development and ripening patterns between the two groups in terms of fruit characteristics and gene expression. Early fruit development in Taiwanese cultivars eSTf and eEllchingf and the Japanese cultivar eHakuof was ahead of that in other three Japanese cultivars (P1). From late April to early May, around the stone-hardening stage, the developmental differences decreased to the same level. Thereafter, Japanese cultivars showed rapid growth, whereas Taiwanese cultivars showed slower growth, reversing the developmental differences between these lines (P2). Ethylene production was not detected until the full ripening stage and was detected for the first time at this stage in five cultivars, except for eEllchingf (P3). In contrast, no ethylene production was observed during the entire duration of fruit development in eEllchingf. A multidimensional scaling plot showed that the overall transcriptome profile changed according to the three stages (P1?P3) of fruit development and ripening. At P1, gene ontologies (GOs) related to cell division, such as the cell cycle and regulation of cyclin-dependent protein serine/threonine kinase activity, were enriched for differentially expressed genes downregulated in Taiwanese cultivars as compared with their expression in Japanese cultivars. At P2, GOs related to fruit development were not enriched, but some genes related to phytohormones, such as auxin, abscisic acid, and cytokinin, which are associated with fruit development and ripening, were differentially expressed. At P3, the expression of genes such as ACS, ACO, and PG, which are involved in ethylene biosynthesis, increased in response to increased ethylene production, but not in eEllchingf, which showed no ethylene production. Expression analysis of 115 NAC (NAM-ATAF1/2-CUC2) family genes, which are related to fruit ripening and ripening date in other fruit species, in the eEllchingf genome revealed changes in expression of NAC056 and NAC073 corresponding to fruit development and ripening in Taiwanese and Japanese cultivars. We discuss the differences in fruit development and ripening behaviors between Taiwanese and Japanese cultivars in terms of physiological and transcriptome changes. en-copyright= kn-copyright= en-aut-name=KashiwamotoTomoaki en-aut-sei=Kashiwamoto en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiTakashi en-aut-sei=Kawai en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OeTakaaki en-aut-sei=Oe en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NumaguchiKoji en-aut-sei=Numaguchi en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraYuto en-aut-sei=Kitamura en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuboYasutaka en-aut-sei=Kubo en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FukudaFumio en-aut-sei=Fukuda en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UshijimaKoichiro en-aut-sei=Ushijima en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Japanese Apricot Laboratory, Wakayama Fruit Tree Experiment Station kn-affil= affil-num=4 en-affil=Japanese Apricot Laboratory, Wakayama Fruit Tree Experiment Station kn-affil= affil-num=5 en-affil=Faculty of Agriculture, Setsunan University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=cell division kn-keyword=cell division en-keyword=ethylene production kn-keyword=ethylene production en-keyword=NAC kn-keyword=NAC en-keyword=phytohormone kn-keyword=phytohormone en-keyword=stone hardening kn-keyword=stone hardening END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=1 article-no= start-page=98 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genetic and phenotypic identities of Staphylococcus coagulans isolated from pustules of dogs with superficial bacterial folliculitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Staphylococcus coagulans, formerly called Staphylococcus schleiferi subsp. coagulans is the second most common isolate from skin lesions of dogs with superficial bacterial folliculitis (SBF). However, the clinical significance of S. coagulans in pustules of canine SBF remains uncertain. This study aimed to investigate the prevalence and genotypic and phenotypic diversity of S. coagulans isolated from pustules in two dogs with SBF.
Results Two dogs with SBF were included in this study. S. schleiferi/coagulans was isolated as the sole organism from three pustules in case #1, whereas it coexisted with S. pseudintermedius in two of seven pustules in case #2. S. pseudintermedius was the sole organism in the remaining five pustules in case #2. Whole genome sequences revealed that all isolates tested were annotated as S. coagulans. The isolates from the same pustules exhibited identical genotypic and phenotypic profiles, indicating clonal multiplication. S. coagulans isolated from different pustules exhibited similar yet distinct genotypic and phenotypic profiles.
Conclusions S. coagulans with identical genetic and phenotypic profiles can be identified as the sole pathogen or coexist with S. pseudintermedius in the pustules of the same dogs with SBF. en-copyright= kn-copyright= en-aut-name=OsumiTakafumi en-aut-sei=Osumi en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShinomiyaYuuki en-aut-sei=Shinomiya en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WanganuttaraThamonwan en-aut-sei=Wanganuttara en-aut-mei=Thamonwan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImanishiIchiro en-aut-sei=Imanishi en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimazakiYotaro en-aut-sei=Shimazaki en-aut-mei=Yotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IyoriKeita en-aut-sei=Iyori en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyodaYoichi en-aut-sei=Toyoda en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IdeKaori en-aut-sei=Ide en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishifujiKoji en-aut-sei=Nishifuji en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=2 en-affil=Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=3 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=5 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=6 en-affil=1sec Co. Ltd. kn-affil= affil-num=7 en-affil=1sec Co. Ltd. kn-affil= affil-num=8 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=9 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology kn-affil= en-keyword=Staphylococcus coagulans kn-keyword=Staphylococcus coagulans en-keyword=Staphylococcus pseudintermedius kn-keyword=Staphylococcus pseudintermedius en-keyword=Dog kn-keyword=Dog en-keyword=Superficial bacterial folliculitis kn-keyword=Superficial bacterial folliculitis en-keyword=Antimicrobial susceptibility kn-keyword=Antimicrobial susceptibility en-keyword=Disk diffusion test kn-keyword=Disk diffusion test END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=5 article-no= start-page=2113 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fgf10 Gene Dosage from a Single Allele Is Insufficient for Forming Multilayered Epithelial Cells in the Murine Lacrimal Gland en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mutations in the fibroblast growth factor 10 (FGF10) gene in humans cause aplasia of the lacrimal and salivary glands (ALSG). In patients with ALSG, heterozygous loss-of-function mutations are found, and FGF10 haploinsufficiency results in the absence of these secretory organs. Lacrimal glands (LGs) are formed through epithelial thickening, budding, and branching morphogenesis. To compare the variable phenotypes of the Fgf10+/? Harderian glands (HGs) previously reported, we examined the development of LGs in wild-type (WT), Fgf10+/?, and Fgf10-null mice. Pax6 immunostaining was performed to visualize the LG primordia from embryonic day 15.5 (E15.5) onwards. In situ hybridization of the genes encoding the epithelial receptor of FGF10, FGFR2b, and its other ligands was performed to determine their potential involvement in LG development. LG primordia were not observed in Fgf10+/? mice bilaterally at E16.5 or later stages. At E15.5, budding from the developing conjunctival epithelium (CE) was observed in a small fraction of the Fgf10+/? LG primordia. In contrast, the Fgf10-null CE failed to promote budding. Among Fgf1, Fgf3, Fgf7, Fgf10, and Fgf22, Fgf10 was expressed in the mesenchyme surrounding developing LG epithelial cells, whereas Fgf1 was expressed in the LG epithelium of WT mice. Fgf7 was initially expressed in the mesenchyme surrounding the nascent LG epithelium, but its expression subsequently became diffused. Thus, we conclude that among the FGFR2b ligands, initial LG formation is dependent on the mesenchymal factors FGF10 and FGF7, and FGF1 is likely to function as an epithelial factor in the LG primordia. A single allele of Fgf10 was found to be insufficient to support the budding process during LG morphogenesis. en-copyright= kn-copyright= en-aut-name=IkedaShiori en-aut-sei=Ikeda en-aut-mei=Shiori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoKeita en-aut-sei=Sato en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TajikaYuki en-aut-sei=Tajika en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujitaHirofumi en-aut-sei=Fujita en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BandoTetsuya en-aut-sei=Bando en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NohnoTsutomu en-aut-sei=Nohno en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyaishiSatoru en-aut-sei=Miyaishi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Gumma Prefectural College of Health Sciences kn-affil= affil-num=4 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Legal Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=fibroblast growth factor kn-keyword=fibroblast growth factor en-keyword=Fgf10 kn-keyword=Fgf10 en-keyword=Fgf1 kn-keyword=Fgf1 en-keyword=Fgf3 kn-keyword=Fgf3 en-keyword=Fgf7 kn-keyword=Fgf7 en-keyword=Fgf22 kn-keyword=Fgf22 en-keyword=Fgfr2b kn-keyword=Fgfr2b en-keyword=mouse kn-keyword=mouse en-keyword=lacrimal gland kn-keyword=lacrimal gland en-keyword=development kn-keyword=development END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1716939 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural analysis of PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte alga Rhodomonas sp. NIES-2332 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Light energy is converted to chemical energy by two photosystems (PSI and PSII) in complex with their light-harvesting complex proteins (LHCI and LHCII) in photosynthesis. Rhodomonas is a member of cryptophyte alga whose LHCs contain unique chlorophyll a/c proteins (ACPs) and phycobiliproteins. We purified PSI-ACPI and PSII-ACPII supercomplexes from a cryptophyte Rhodomonas sp. NIES-2332 and analyzed their structures at high resolutions of 2.08 ? and 2.17 ?, respectively, using cryo-electron microscopy. These structures are largely similar to those reported previously from two other species of cryptophytes, but exhibited some differences in both the pigment locations and subunit structures. A part of the antenna subunits of both photosystems is shifted compared with the previously reported structures from other species of cryptophytes, suggesting some differences in the energy transfer rates from the antenna to the PSI and PSII cores. Newly identified lipids are found to occupy the interfaces between the antennae and cores, which may be important for assembly and stabilization of the supercomplexes. Water molecules surrounding three iron-sulfur clusters of the PSI core are found in our high-resolution structure, some of which are conserved from cyanobacteria to higher plants but some are different. In addition, our structure of PSII-ACPII lacks the subunits of oxygen-evolving complex as well as the Mn4CaO5 cluster, suggesting that the cells are in the S-growth phase, yet the PSI-ACPI structure showed the binding of PsaQ, suggesting that it is in an L-phase. These results suggest that the S-phase and L-phase can co-exist in the cryptophytic cells. The high-resolution structures of both PSI-ACPIs and PSII-ACPIIs solved in this study provide a more solid structural basis for elucidating the energy transfer and quenching mechanisms in this group of the organisms. en-copyright= kn-copyright= en-aut-name=ZhangWenyue en-aut-sei=Zhang en-aut-mei=Wenyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoneharaNozomi en-aut-sei=Yonehara en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiiMizuki en-aut-sei=Ishii en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=JiangHaowei en-aut-sei=Jiang en-aut-mei=Haowei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=La RoccaRomain en-aut-sei=La Rocca en-aut-mei=Romain kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsaiPi-Cheng en-aut-sei=Tsai en-aut-mei=Pi-Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AkitaFusamichi en-aut-sei=Akita en-aut-mei=Fusamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Advanced Research Field, Research Institute for Interdisciplinary Science, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=cryptophytes kn-keyword=cryptophytes en-keyword=Rhodomonas kn-keyword=Rhodomonas en-keyword=photosystem I kn-keyword=photosystem I en-keyword=photosystem II kn-keyword=photosystem II en-keyword=light-harvesting complex kn-keyword=light-harvesting complex en-keyword=photosynthesis kn-keyword=photosynthesis END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=13 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background C1orf50 encodes a small, evolutionarily conserved protein, the function of which remains unclear. Its significance across various human cancers, particularly its specific role in ovarian cancer within an immunogenomic context, is not yet fully understood. Utilizing The Cancer Genome Atlas and single-cell RNA sequencing (scRNA-seq) public datasets, we conducted a comprehensive profiling of C1orf50 across multiple cancer types, with a particular focus on ovarian cancer, to investigate its associations with copy-number status, genomic instability, tumor programs, and the immune microenvironment.
Results Across cancer types, copy-number gain or amplification of C1orf50 was most frequent in ovarian cancer and closely tracked with higher messenger RNA levels. Higher C1orf50 expression was associated with a greater tumor mutational burden and homologous recombination deficiency, as indicated by gene-set patterns that suggested heightened cell-cycle and cellular stress responses accompanied by reduced oxidative phosphorylation, enrichment of regulatory T cells, and depletion of resting memory CD4 T cells. In ovarian cancer, focal events at chromosome 1p34.2 were accompanied by stepwise increases in C1orf50 expression by clinical stage and were linked to higher tumor mutational burden, homologous recombination deficiency, and greater loss of heterozygosity, together with more frequent gene alterations in BRCA1 or BRCA2. Immune composition clustered into profiles consistent with an immunosuppressive context in tumors with higher C1orf50 expression. The scRNA-seq data further revealed that cancer cells enhanced immune-suppressive interactions with various immune cell populations and diminished antigen-presentation signals. Analyses of genomic instability in ovarian cancer suggested mutational processes compatible with base-substitution patterns associated with cytidine deaminase activity and with insertion-deletion patterns characteristic of homologous recombination failure, while transcript-level patterns pointed to a broad downshift of canonical DNA repair activity with apparent compensatory adjustments in related pathways rather than a uniform change in any single pathway.
Conclusions The overexpression of C1orf50 characterizes an aggressive immunogenomic phenotype in ovarian cancer, distinguished by genomic instability, impaired DNA repair mechanisms, and extensive immunosuppression. These findings indicate that C1orf50 warrants consideration as a potential biomarker and a prospective target for therapeutic investigation. Furthermore, they advocate for the progression to prospective validation and functional studies to ascertain its clinical significance. en-copyright= kn-copyright= en-aut-name=RogachevskayaAnna en-aut-sei=Rogachevskaya en-aut-mei=Anna 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=OhtsuAkira en-aut-sei=Ohtsu en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChinVanessa D. en-aut-sei=Chin en-aut-mei=Vanessa D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Pe?aTirso en-aut-sei=Pe?a en-aut-mei=Tirso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AraiSeiji en-aut-sei=Arai en-aut-mei=Seiji 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=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Harvard Medical School kn-affil= affil-num=4 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=6 en-affil=Department of Urology, Gunma University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Molecular Physiology, Faculty of Medicine, Graduate School of Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=Pan-cancer analysis kn-keyword=Pan-cancer analysis en-keyword=DNA repair kn-keyword=DNA repair en-keyword=Gene expression kn-keyword=Gene expression en-keyword=Tumor microenvironment kn-keyword=Tumor microenvironment en-keyword=Immune evasion kn-keyword=Immune evasion en-keyword=Single-cell RNA-seq kn-keyword=Single-cell RNA-seq 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? 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 Childrenfs Medical Center kn-affil= affil-num=7 en-affil=Division of Infectious Diseases and Immunology, Saitama Childrenfs 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=17 cd-vols= no-issue=9 article-no= start-page=4363 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gaseous CO2 electrolysis: latest advances in electrode and electrolyzer technologies toward abating CO2 emissions en-subtitle= kn-subtitle= en-abstract= kn-abstract=The conversion of CO2 into multicarbon (C2+) products via electrochemical reduction is considered a key technology for the sustainable production of fuels and chemicals. The performance of high-rate gaseous CO2 electrolysis is governed by interrelated factors such as the electrocatalysts, electrodes, electrolytes, and cell architectures. Despite the intensive focus on catalyst research, systematic studies addressing the other components remain scarce, leaving critical gaps in our understanding toward achieving higher performance in CO2 electrolysis systems. The nanoscale design of catalyst surface electronic structures and the macroscale design of electrodes and electrolyzer architectures both influence the overall activity of the electrochemical system. In designing macroscale components, it is necessary to establish benchmarks based on a comprehensive evaluation of CO2 emissions for the entire electrolysis process, because these parameters are directly linked to output metrics such as current density and cell voltage under practical operating conditions. This review summarizes recent advances in electrodes and electrolyzers, and through life-cycle assessment (LCA), evaluates key performance indicators (KPIs) for achieving negative emissions and assesses the current technology readiness of CO2 electrolysis. en-copyright= kn-copyright= en-aut-name=KamiyaKazuhide en-aut-sei=Kamiya en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakasoneSora en-aut-sei=Nakasone en-aut-mei=Sora kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuriharaRyo en-aut-sei=Kurihara en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueAsato en-aut-sei=Inoue en-aut-mei=Asato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IrieHazuki en-aut-sei=Irie en-aut-mei=Hazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakahataShoko en-aut-sei=Nakahata en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TaniguchiSatoshi en-aut-sei=Taniguchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NguyenThuy T. H. en-aut-sei=Nguyen en-aut-mei=Thuy T. H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaSho en-aut-sei=Kataoka en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=2 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=3 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=4 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=5 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=6 en-affil=Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=8 en-affil=Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 kn-affil= affil-num=9 en-affil=Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 kn-affil= affil-num=10 en-affil=Research Institute for Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Central 5 kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=6 article-no= start-page=1128 end-page=1136 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surgery for Older Cancer Patients: Cross]Organ Review and Good Practice Statement by the Japanese Geriatric Oncology Guideline Committee en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although the number of older people is increasing, there is a lack of evidence and insufficient consensus regarding postoperative complications and survival in older cancer patients. In this study, we conducted a literature search and systematic review focusing on the outcomes after surgery for older cancer patients.
Methods: Literature focusing on surgical treatment for older cancer patients was extracted from Japanese clinical practice guidelines for gastric cancer, lung cancer, colorectal cancer, liver cancer, and gynecological cancers (uterine body, uterine cervix, ovary, and external genitalia and vagina). Outcomes were reviewed, and committee members determined the strength of evidence on a four-point scale (A to D), with A being the highest and D being the lowest.
Results: Older cancer patients tend to have a higher incidence of postoperative complications and postoperative syndromes, and their expected survival is generally shorter compared to non-older patients. When extensive surgeries such as para-aortic lymph node dissection and/or resection with other organs are performed for older cancer patients, the postoperative mortality rates tend to increase compared to non-older patients.
Conclusion: Surgical treatments for older cancer patients tend to result in higher morbidity even when the patients are in good health status. Nevertheless, there is still a possibility that a certain fraction of the patients achieve treatment outcomes comparable to those of non-older patients. Therefore, surgical indication and procedure for older cancer patients should be carefully determined based on surgical invasiveness and patient tolerability. en-copyright= kn-copyright= en-aut-name=TanakaChie en-aut-sei=Tanaka en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OfuchiTakashi en-aut-sei=Ofuchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueDaisuke en-aut-sei=Inoue en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugimotoKen en-aut-sei=Sugimoto en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurofushiKeiko en-aut-sei=Murofushi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkuyamaToru en-aut-sei=Okuyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanukiShigeaki en-aut-sei=Watanuki en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ImamuraChiyo en-aut-sei=Imamura en-aut-mei=Chiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakaiDaisuke en-aut-sei=Sakai en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakuraiNaomi en-aut-sei=Sakurai en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeKiyotaka en-aut-sei=Watanabe en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TamuraKazuo en-aut-sei=Tamura en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SaekiToshiaki en-aut-sei=Saeki en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IshiguroHiroshi en-aut-sei=Ishiguro en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Surgery, Kyushu University Beppu Hospital kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, University of Fukui kn-affil= affil-num=5 en-affil=Department of General Geriatric Medicine, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=7 en-affil=Department of Psychiatry/Palliative Care Center, Nagoya City University West Medical Center kn-affil= affil-num=8 en-affil=National Center for Global Health and Medicine, National College of Nursing kn-affil= affil-num=9 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=10 en-affil=Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Cancer Solutions Co. Ltd kn-affil= affil-num=12 en-affil=Division of Medical Oncology, Department of Medicine, School of Medicine, Teikyo University kn-affil= affil-num=13 en-affil=NPO Clinical Hematology/Oncology Treatment Study Group kn-affil= affil-num=14 en-affil=Breast Oncology Service, Saitama Medical University International Medical Center kn-affil= affil-num=15 en-affil=Breast Oncology Service, Saitama Medical University International Medical Center kn-affil= en-keyword=cancer kn-keyword=cancer en-keyword=older patients kn-keyword=older patients en-keyword=surgery kn-keyword=surgery END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=9 article-no= start-page=113274 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Extensive urine production in euryhaline red stingray for adaptation to hypoosmotic environments en-subtitle= kn-subtitle= en-abstract= kn-abstract=Maintaining water balance is a prerequisite for all organisms. Euryhaline elasmobranchs face the severest water-influx potential in fresh water (FW), as they retain high concentrations of urea even in hypotonic environments. To elucidate how they overcome this osmotic challenge, we assessed urine output in conscious euryhaline red stingrays (Hemitrygon akajei). Following acclimation to 5% diluted seawater, the stingrays increased urinary output by 87-fold?the greatest change observed in vertebrates?partly due to 6.8-fold increase in glomerular filtration rate (GFR). In the nephron, expressions of Aquaporin-1 (Aqp1), Aqp3, and Aqp15 were strongly downregulated in FW, indicating that tubular diuresis bridges the gap between GFR and final urine volume. Meanwhile, FW-acclimation upregulated Aqp1 and Aqp4 in the distinct bundle structure, which promotes urea reabsorption. Euryhaline elasmobranchs resolve the huge osmotic challenge of FW by excreting massive amounts of water and retaining osmolytes including urea through coordinated regulation of GFR and Aqp expressions. en-copyright= kn-copyright= en-aut-name=AburataniNaotaka en-aut-sei=Aburatani en-aut-mei=Naotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakagiWataru en-aut-sei=Takagi en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WongMarty Kwok-Shing en-aut-sei=Wong en-aut-mei=Marty Kwok-Shing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgawaNobuhiro en-aut-sei=Ogawa en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurakuShigehiro en-aut-sei=Kuraku en-aut-mei=Shigehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoMana en-aut-sei=Sato en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoKazuhiro en-aut-sei=Saito en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GodoWaichiro en-aut-sei=Godo en-aut-mei=Waichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HyodoSusumu en-aut-sei=Hyodo en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo 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=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Genomics and Evolutionary Biology, National Institute of Genetics kn-affil= affil-num=6 en-affil=Department of Genomics and Evolutionary Biology, National Institute of Genetics kn-affil= affil-num=7 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= affil-num=8 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= affil-num=9 en-affil=Ushimado Marine Institute, Faculty of Science, Okayama University kn-affil= affil-num=10 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= en-keyword=Zoology kn-keyword=Zoology en-keyword=Biochemistry kn-keyword=Biochemistry en-keyword=Animal Physiology kn-keyword=Animal Physiology END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue= article-no= start-page=1 end-page=51 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Current situation and issues of core organization in Adult Gurdianship System kn-title=¬”NŒãŒ©§“x@`’†Šj‹@ŠÖ‚ÌŒ»ó‚Ɖۑè` en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NISHIDAKazuhiro en-aut-sei=NISHIDA en-aut-mei=Kazuhiro kn-aut-name=¼“c˜aO kn-aut-sei=¼“c kn-aut-mei=˜aO aut-affil-num=1 ORCID= en-aut-name=NISHIYAMAMika en-aut-sei=NISHIYAMA en-aut-mei=Mika kn-aut-name=¼ŽRŽO‰À kn-aut-sei=¼ŽR kn-aut-mei=ŽO‰À aut-affil-num=2 ORCID= en-aut-name=NAGASHIOAyaka en-aut-sei=NAGASHIO en-aut-mei=Ayaka kn-aut-name=’·‰–Ê kn-aut-sei=’·‰– kn-aut-mei=Ê aut-affil-num=3 ORCID= en-aut-name=YOSHIOKAKyosuke en-aut-sei=YOSHIOKA en-aut-mei=Kyosuke kn-aut-name=‹g‰ª‹œ—S kn-aut-sei=‹g‰ª kn-aut-mei=‹œ—S aut-affil-num=4 ORCID= en-aut-name=IMAITomono en-aut-sei=IMAI en-aut-mei=Tomono kn-aut-name=¡ˆä—F”T kn-aut-sei=¡ˆä kn-aut-mei=—F”T aut-affil-num=5 ORCID= en-aut-name=MIZUTAYuji en-aut-sei=MIZUTA en-aut-mei=Yuji kn-aut-name=…“c—Y“ñ kn-aut-sei=…“c kn-aut-mei=—Y“ñ aut-affil-num=6 ORCID= en-aut-name=UCHIDADaisuke en-aut-sei=UCHIDA en-aut-mei=Daisuke kn-aut-name=“à“c‘å‰î kn-aut-sei=“à“c kn-aut-mei=‘å‰î aut-affil-num=7 ORCID= affil-num=1 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@–@–±Œ¤‹†‰È affil-num=2 en-affil=Okayama City Adult Gurdianship Center Case kn-affil=‰ªŽRŽsŽÐ‰ï•ŸŽƒ‹¦‹c‰ï‰ªŽRŽs¬”NŒãŒ©ƒZƒ“ƒ^[ affil-num=3 en-affil=Okayama City Adult Gurdianship Center Case kn-affil=‰ªŽRŽsŽÐ‰ï•ŸŽƒ‹¦‹c‰ï‰ªŽRŽs¬”NŒãŒ©ƒZƒ“ƒ^[ affil-num=4 en-affil=Soja City Case kn-affil=‘ŽÐŽsŽÐ‰ï•ŸŽƒ‹¦‹c‰ï affil-num=5 en-affil=Chita Area Avocacy Center Case kn-affil=’m‘½’nˆæŒ —˜—iŒìŽx‰‡ƒZƒ“ƒ^[ affil-num=6 en-affil=Oda City Case kn-affil=‘å“cŽsŽÐ‰ï•ŸŽƒ‹¦‹c‰ï‘å“cŽs¬”NŒãŒ©ƒZƒ“ƒ^[ affil-num=7 en-affil=Oda City Case kn-affil=‘å“cŽs‰îŒì•ÛŒ¯‰Û END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue= article-no= start-page=47 end-page=60 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ultrafast Time-Compressive CMOS Image Sensors Based on Multitap Charge Modulators for Filming Light-In Flight en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ultrafast time-compressive CMOS image sensors based on multitap charge modulators can capture light-in flight using coded exposure masks on the focal plane. Transient images can then be reconstructed using iterative methods or deep learning models. Although the image sensor is based on indirect time-of-flight (ToF) image sensors, the reconstructed images are equivalent to those captured by direct ToF (D-ToF) image sensors. Important design parameters of the image sensor include the pixel block size and the number of taps of the charge modulator. Several constraints regarding the charge transfer of the multitap charge modulator, the hamming distance between exposure codes at adjacent timings, and the minimal time window duration must be considered when designing exposure codes. The influence of these factors on the fidelity of the reconstructed images is analyzed numerically. The results show that a pixel block size of 4~4 is optimal and that four or more taps are required for light detection and ranging (LiDAR) applications when 32 transient images of light-in flight are reconstructed. To demonstrate LiDAR in a scene with multipath interference, two objects were observed through a weakly diffusive sheet. The temporal resolution, as defined by the clock period of the exposure codes, was 1.65 ns. Multiple reflections were reconstructed using an iterative method (TVAL3) and a deep learning model (ADMM-Net). Although the waveforms of optical pulses reconstructed by TVAL3 are distorted, the amplitudes are more accurate. Conversely, although ADMM-Net reconstructs sharper optical pulses, the amplitudes are inaccurate. To achieve the shorter temporal resolution required for time-resolved diffuse optical tomography (DOT) and fluorescence lifetime imaging (FLIm), the feasibility of heterodyne compression was demonstrated through simulation. en-copyright= kn-copyright= en-aut-name=KagawaKeiichiro en-aut-sei=Kagawa en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiDaisuke en-aut-sei=Hayashi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakakuraArashi en-aut-sei=Takakura en-aut-mei=Arashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UmekiYuto en-aut-sei=Umeki en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaMichitaka en-aut-sei=Yoshida en-aut-mei=Michitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YasutomiKeita en-aut-sei=Yasutomi en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawahitoShoji en-aut-sei=Kawahito en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChaeYoungcheol en-aut-sei=Chae en-aut-mei=Youngcheol kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NagaharaHajime en-aut-sei=Nagahara en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Research Institute of Electronics, Shizuoka University kn-affil= affil-num=2 en-affil=Graduate School of Integrated Science and Technology, Shizuoka University kn-affil= affil-num=3 en-affil=Faculty of Engineering, Shizuoka University kn-affil= affil-num=4 en-affil=Graduate School of Integrated Science and Technology, Shizuoka University kn-affil= affil-num=5 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Research Institute of Electronics, Shizuoka University kn-affil= affil-num=7 en-affil=Research Institute of Electronics, Shizuoka University kn-affil= affil-num=8 en-affil=Department of Electrical and Electronic Engineering, Yonsei University kn-affil= affil-num=9 en-affil=D3 Center, The University of Osaka kn-affil= en-keyword=CMOS image sensor kn-keyword=CMOS image sensor en-keyword=compressive imaging kn-keyword=compressive imaging en-keyword=computational photography (CP) kn-keyword=computational photography (CP) en-keyword=multitap charge modulator kn-keyword=multitap charge modulator en-keyword=transient imaging kn-keyword=transient imaging 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=30 cd-vols= no-issue=7 article-no= start-page=1259 end-page=1267 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=How to report and discuss subgroup analyses in clinical practice guidelines? Evaluation procedure of the clinical and statistical relevancy en-subtitle= kn-subtitle= en-abstract= kn-abstract=The results of subgroup analyses of clinical trials are important reference information when considering the generalizability of a study treatment, i.e., providing the best treatment for each individual patient. The results of subgroup analyses are often presented in publications, etc. as forest plots focusing on patient backgrounds. However, it is important to fully understand and grasp some of the issues involved in subgroup analyses and to interpret the results carefully to apply them in clinical practice. Although the literature includes some reports on how subgroup analyses should be evaluated and handled for the purpose of establishing medical practice guidelines, most of the papers have mainly evaluated the reliability of subgroup analyses from a statistical perspective; few of them have incorporated clinical importance in their evaluations. Therefore, in December 2019, we established a Subgroup Analysis Review Committee consisting of oncologists specializing in lung cancer treatment and statistical experts among the members of the Guidelines Review Committee of the Japanese Lung Cancer Association, with the aim of appropriately reflecting subgroup analysis in Japanese lung cancer practice guidelines. We developed a new evaluation strategy to incorporate clinical aspects as well as reliability assessment. Specifically, on the basis of a clinical and statistical review of the problems with subgroup analyses presented as clinical trial results, we developed criteria and procedures to ensure consistency and fairness in the citation of clinical guidelines. en-copyright= kn-copyright= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiuraSatoru en-aut-sei=Miura en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OyaYuko en-aut-sei=Oya en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=TanakaKentaro en-aut-sei=Tanaka en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TeraokaShunsuke en-aut-sei=Teraoka en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoriseMasahiro en-aut-sei=Morise en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoritaSatoshi en-aut-sei=Morita en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Niigata Cancer Center Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine and Allergy, Fujita Health University kn-affil= affil-num=4 en-affil=Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori University kn-affil= affil-num=5 en-affil=Graduate School of Medical Sciences, Research Institute for Diseases of the Chest, Kyushu University kn-affil= affil-num=6 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=Subgroup analysis kn-keyword=Subgroup analysis en-keyword=Guideline kn-keyword=Guideline en-keyword=Lung cancer kn-keyword=Lung cancer END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=e86575 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Retreatment With EGFR-Tyrosine Kinase Inhibitor After Disease Progression Following Gefitinib Induction and Chemoradiotherapy in EGFR-Mutant Stage III Non-small Lung Cancer: An Efficacy and Safety Analysis of the LOGIK0902/OLCSG0905 Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and objective: We had previously conducted a phase II study (LOGIK0902/OLCSG0905 study) involving the eight-week administration of gefitinib, followed by cisplatin-based chemoradiotherapy, to treat locally advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC). Despite favorable overall survival outcomes, more than half of the patients relapsed after the protocol therapy, highlighting the need to clarify the clinical significance of retreatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated the efficacy and safety of EGFR-TKI retreatment after disease progression.
Materials and methods: We included 14 patients who relapsed after the protocol treatment and received any type of EGFR-TKI as post-progression treatment in this sub-analysis. We evaluated the efficacy and safety of retreatment with EGFR-TKI in these patients.
Results: Among the 14 patients, 11 (78.6%) responded to the induction of gefitinib in the treatment protocol. After relapse, 9/14 patients (64.3%) received gefitinib, 3/14 (21.4%) received afatinib, and 2/14 (14.3%) received erlotinib monotherapy, respectively. The median duration of post-progression EGFR-TKI treatment was 17.9 (0.7-45.5) months. The overall response rate (ORR) and disease control rate were 64.3% [9/14 patients; 95% confidence interval (CI): 35.1%-87.2%] and 85.7% (12/14 patients; 95% CI: 57.2%-98.2%), respectively. The median progression-free survival (PFS) and median survival durations after the initiation of EGFR-TKI retreatment were 11.8 months (95% CI: 5.7-20.7 months) and 47.4 months (95% CI: 31.8 months to not estimable), respectively. Adverse events were comparable to those previously reported.
Conclusions: Patients with disease progression after protocol therapy demonstrated sensitivity to retreatment with an EGFR-TKI, with acceptable safety. en-copyright= kn-copyright= en-aut-name=SaekiSho en-aut-sei=Saeki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakataShinya en-aut-sei=Sakata en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TamuraTomoki en-aut-sei=Tamura en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyozawaRyo en-aut-sei=Toyozawa en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaradaDaijiro en-aut-sei=Harada en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaKentaro en-aut-sei=Tanaka en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShioyamaYoshiyuki en-aut-sei=Shioyama en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GembaKenichi en-aut-sei=Gemba en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SasakiTomonari en-aut-sei=Sasaki en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=BesshoAkihiro en-aut-sei=Bessho en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KishimotoJunji en-aut-sei=Kishimoto en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SugioKenji en-aut-sei=Sugio en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=2 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Kumamoto 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 Respiratory Medicine, Kitakyushu Municipal Medical Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=11 en-affil=Radiation Oncology, Ion Beam Therapy Center, SAGA HIMAT Foundation kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=13 en-affil=Department of Radiation Oncology, Iizuka Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=15 en-affil=Center for Clinical and Translational Research, Kyushu University Hospital kn-affil= affil-num=16 en-affil=Department of Radiology, Division of Radiation Oncology, Kawasaki Medical School kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Thoracic and Breast Surgery, Oita University kn-affil= en-keyword=chemoradiotherapy kn-keyword=chemoradiotherapy en-keyword=egfr kn-keyword=egfr en-keyword=locally advanced setting kn-keyword=locally advanced setting en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=progression kn-keyword=progression en-keyword=retreatment kn-keyword=retreatment en-keyword=safety kn-keyword=safety en-keyword=targeted therapy kn-keyword=targeted therapy END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=14 article-no= start-page=2155 end-page=2159 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Myeloid Sarcoma in the Small Intestine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Myeloid sarcoma is a rare extramedullary tumor of immature myeloid cells that is often associated with acute myeloid leukemia (AML). We herein report an 81-year-old man who presented with intestinal obstruction due to myeloid sarcoma of the small intestine. Diagnostic challenges were overcome using double-balloon enteroscopy and a biopsy, which confirmed the diagnosis of myeloid sarcoma. The patient subsequently developed AML but responded well to chemotherapy. This case underscores the importance of considering myeloid sarcoma in the differential diagnosis of small-bowel tumors. Highlighting the significance of a histological analysis, even in patients presenting with small bowel obstruction, the early diagnosis and treatment are crucial for improving outcomes, particularly in patients without a history of hematologic malignancies. 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=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirataShoichiro en-aut-sei=Hirata en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuedaKatsunori en-aut-sei=Matsueda en-aut-mei=Katsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KametakaDaisuke en-aut-sei=Kametaka en-aut-mei=Daisuke 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=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of 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 Pathology, 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= en-keyword=acute myeloid leukemia kn-keyword=acute myeloid leukemia en-keyword=double-balloon enteroscopy kn-keyword=double-balloon enteroscopy en-keyword=myeloid sarcoma kn-keyword=myeloid sarcoma en-keyword=small intestine kn-keyword=small intestine END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=2 article-no= start-page=363 end-page=368 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microsatellite-high intrahepatic cholangiocarcinoma with favorable treatment outcome using pembrolizumab en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intrahepatic cholangiocarcinoma has a poor prognosis. In unresectable cases, the survival period is short despite combination therapy with cytotoxic anticancer agents and immune checkpoint inhibitors. The usefulness of immune checkpoint inhibitors against malignant tumors with microsatellite instability-high (MSI-H) mutations was shown in the KEYNOTE158 study; however, data for intrahepatic cholangiocarcinoma are insufficient. In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. A comprehensive cancer genomic profiling (CGP) test showed MLH1 pathogenic mutation and MSI-H. When pembrolizumab was administered, the tumor shrinkage effect was rapidly observed, which was sustained even after 30 months. No pathogenic mutations were observed in the germline test, and MSI-high was considered to be due to the MLH1 pathogenic mutation occurring sporadically in somatic cells. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed. en-copyright= kn-copyright= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru 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=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimotoKosaku en-aut-sei=Morimoto en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TerasawaHiroyuki en-aut-sei=Terasawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki 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 Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=Microsatellite instability (MSI)-high kn-keyword=Microsatellite instability (MSI)-high en-keyword=Tumor mutation burden (TMB)-high kn-keyword=Tumor mutation burden (TMB)-high en-keyword=Intrahepatic cholangiocarcinoma kn-keyword=Intrahepatic cholangiocarcinoma en-keyword=Comprehensive genome profiling kn-keyword=Comprehensive genome profiling END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=2 article-no= start-page=e79651 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gastric Metastasis of Renal Cell Carcinoma Initially Diagnosed by Esophagogastroduodenoscopy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Here, we report a rare case of renal cell carcinoma (RCC) initially detected as a gastric metastasis. A 58-year-old man with epigastric discomfort underwent esophagogastroduodenoscopy, which revealed a reddish semi-pedunculated lesion with a whitish coating. Biopsy and imaging confirmed clear cell RCC metastasis. Contrast-enhanced computed tomography (CT) revealed a primary renal tumor with pancreatic and lymph node metastases. Despite chemotherapy treatment, the patient died after 10 months. Gastric metastases from RCC, although rare, should be considered in highly vascular gastric lesions with white coatings. Clinicians must be vigilant for metastatic diseases with atypical gastric findings. 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=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirataShoichiro en-aut-sei=Hirata en-aut-mei=Shoichiro 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=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of 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 Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=clear renal cell carcinoma kn-keyword=clear renal cell carcinoma en-keyword=esophagogastroduodenoscopy (egd) kn-keyword=esophagogastroduodenoscopy (egd) en-keyword=gastric metastasis kn-keyword=gastric metastasis en-keyword=metastatic tumor, renal cell carcinoma (rcc) kn-keyword=metastatic tumor, renal cell carcinoma (rcc) END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue= article-no= start-page=9 end-page=12 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260301 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Soil nitrogen dynamics affected by the fine roots of canopy trees in Eastern Hokkaido, Japan kn-title=–kŠC“¹“Œ•”‚ÌX—Ñ‚É‚¨‚¢‚Ä—ÑŠ¥–Ø‚Ìת‚ª“yë’‚‘f“®‘Ô‚É—^‚¦‚é‰e‹¿ en-subtitle= kn-subtitle= en-abstract= kn-abstract=@Plants release mixtures of labile organic matter from their fine roots (root exudates) into the surrounding soil (rhizosphere). Partly due to the release of root exudates, microbial community structures and their activities within the rhizosphere differ significantly from those in other soil areas (bulk soil). Consequently, nutrient cycling processes, including nitrogen mineralization, are accelerated in the rhizosphere, facilitating nutrient acquisition by plants. This phenomenon, known as the rhizosphere effect, has been repeatedly reported in studies of herbaceous plants; however, the impact of canopy tree fine roots on soil nitrogen dynamics through the effect in forest ecosystems remains largely unknown. Here, I introduce our research investigating the root exudates and rhizosphere effects of the fine roots of canopy trees, Quercus crispula, and how these fine roots affect soil nitrogen dynamics. The quantity of root exudates varied daily rather than seasonally, with solar radiation having a strong and positive effect on the amounts. However, even after leaf fall, root exudation was observed. In the rhizosphere, specific bacterial communities were present regardless of season, while ectomycorrhizal fungal populations were higher than in the bulk soil only in summer. Extracellular enzymatic activity relating to nitrogen cycling was higher in the rhizosphere than in the bulk soil across seasons. Nitrogen uptake by the tree was likely lower in winter and spring, leading to labile nitrogen accumulation in the rhizosphere during these periods. On an annual basis, however, the impact of fine roots on apparent inorganic nitrogen dynamics was minor. These results suggest that the canopy tree, Q. crispula, accelerates soil nitrogen cycling through root exudation and rhizosphere effects, regardless of season, while the acceleration of the cycle and the utilization of available nitrogen are well-balanced annually, thereby avoiding unnecessary carbon investment. en-copyright= kn-copyright= en-aut-name=NakayamaMasataka en-aut-sei=Nakayama en-aut-mei=Masataka kn-aut-name=’†ŽR—’q kn-aut-sei=’†ŽR kn-aut-mei=—’q aut-affil-num=1 ORCID= affil-num=1 en-affil=Course of Environmental Ecology kn-affil=ŠÂ‹«¶‘ÔŠwƒR[ƒX en-keyword=Quercus crispula kn-keyword=Quercus crispula en-keyword=root exudates kn-keyword=root exudates en-keyword=rhizosphere effect kn-keyword=rhizosphere effect en-keyword=nitrogen dynamics kn-keyword=nitrogen dynamics en-keyword=nitrogen uptake kn-keyword=nitrogen uptake END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue= article-no= start-page=1 end-page=8 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260301 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of Branching Characteristics and Their Contribution to Yield in Everbearing Strawberry Cultivars under Forced Cultivation en-subtitle= kn-subtitle= en-abstract= kn-abstract=@Enhancing continuous flowering in cultivated strawberries may result in insufficient photosynthetic products due to the lower limit of leaf number on each lateral shoot, leading to reduced yield and fruit quality. If strawberries could differentiate an appropriate number of tillers and allow each tiller to grow autonomously with sufficient leaf number on each lateral shoot, rather than flowering continuously on the main bud alone, plants could achieve high yields while preventing plant weakening and fruit quality deterioration. Therefore, this study evaluated branching characteristics of everbearing strawberry cultivars under forcing cultivation to identify cultivars with moderate tillering and moderately low continuous flowering. Pot experiments revealed that the number of tillers was high in eSummer Princessf and eMiyazaki-natsuharukaf but low in eSummer Berryf and eSuzuakanef. This trend was independent of total number of lateral shoots, nodal position of first inflorescence, and the number of leaves on each lateral shoot, which serve as indicators of continuous flowering ability. Among seven tested cultivars, eDT17f and eMiyazaki-natsuharukaf showed intermediate values with 2.1 - 2.5 tillers per plant and 6.7 - 7.7 leaves on each lateral shoots. These cultivars showed yields of 747.0 - 1,028.5 g per plant under forcing cultivation, which were higher than other cultivars, along with consistent fruit quality. These results suggest that improving branching characteristics is a practical approach to enhancing fruit productivity in strawberries. en-copyright= kn-copyright= en-aut-name=Hikawa-EndoMinori en-aut-sei=Hikawa-Endo en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SoneKazuyoshi en-aut-sei=Sone en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorishitaMasami en-aut-sei=Morishita en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Kyushu Okinawa Region Agricultural Research Center, NARO kn-affil= affil-num=2 en-affil=Kyushu Okinawa Region Agricultural Research Center, NARO kn-affil= affil-num=3 en-affil=Kyushu Okinawa Region Agricultural Research Center, NARO kn-affil= en-keyword=branching characteristics kn-keyword=branching characteristics en-keyword=continuous flowering ability kn-keyword=continuous flowering ability en-keyword=crown kn-keyword=crown en-keyword=strawberry kn-keyword=strawberry en-keyword=tiller kn-keyword=tiller END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue= article-no= start-page=145 end-page=154 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Chi no Tanken (Inquiries of Knowledge) meets Multicultural Collaborative LearningFTransforming a Japanese Online Course for Global Learners kn-title=u’m‚Ì’TŒ¤v~ ‘½•¶‰»‹¤C \ƒIƒ“ƒ‰ƒCƒ“Žö‹ÆÄ\’z‚ÌŽŽ‚Ý\ en-subtitle= kn-subtitle= en-abstract=Okayama University launched a new undergraduate curriculum in April 2025. As part of this reform, Chi no Tanken, a general education course required for incoming students, was introduced. This paper reports on the first-year implementation of the course, offered in English as Inquiries of Knowledge, for students in the Discovery Program for Global Learners, many of whom are international students. Reconstructing the on-demand online course from a multicultural collaborative learning perspective required more than simply translating the materials into English. It also necessitated developing pedagogical strategies to foster collaborative learning in the online environment and to integrate linguistic and cultural considerations. kn-abstract=‰ªŽR‘åŠw‚Å‚Í2025”N4ŒŽ“üŠw¶‚©‚çVƒJƒŠƒLƒ…ƒ‰ƒ€‚ªƒXƒ^[ƒg‚µ‚½BŠwŽm‰Û’ö‰üŠv‚̈êŠÂ‚Æ‚µ‚Ä“±“ü‚³‚ꂽ‚Ì‚ª‘SŠw‹¤’ÊE‰Û‘è’T‹†‰È–Úu’m‚Ì’TŒ¤v‚Å‚ ‚éB–{e‚Å‚ÍCV“ü¶‘ÎۉȖڂł ‚éu’m‚Ì’TŒ¤v‚ðCŠCŠO¶‚ðŠÜ‚ÞƒOƒ[ƒoƒ‹EƒfƒBƒXƒJƒoƒŠ[EƒvƒƒOƒ‰ƒ€¶Œü‚¯‚ɉpŒê‚Å gInquiries of Knowledgeh ‚Æ‚µ‚ÄŠJu‚µ‚½‰”N“x‚ÌŽæ‚è‘g‚Ý‚ð•ñ‚·‚éB‚Æ‚è‚킯ƒIƒ“ƒfƒ}ƒ“ƒhŒ^ƒIƒ“ƒ‰ƒCƒ“Žö‹Æ‚ð, –{Šw‚ª„i‚·‚鑽•¶‰»‹¤C‚ÌŽ‹“_‚ÅÄ\’z‚·‚é‚É‚ ‚½‚èC‹³Þ‚ð’P‚ɉp–ó‚·‚é‚Ì‚Å‚Í‚È‚­, ƒIƒ“ƒ‰ƒCƒ“ŠÂ‹«‚É‚¨‚¢‚Ä‚à‹¦“­ŠwK‚ðŽÀŒ»‚·‚éH•v‚âCŒ¾Œê“IE•¶‰»“I”z—¶‚Ì“‡‚ª•s‰ÂŒ‡‚Å‚ ‚邱‚Ƃ𖾂炩‚É‚·‚éB en-copyright= kn-copyright= en-aut-name=YAMAMOTOYumiko en-aut-sei=YAMAMOTO en-aut-mei=Yumiko kn-aut-name=ŽR–{—R”üŽq kn-aut-sei=ŽR–{ kn-aut-mei=—R”üŽq aut-affil-num=1 ORCID= en-aut-name=NGUYENKha Manh en-aut-sei=NGUYEN en-aut-mei=Kha Manh kn-aut-name=ƒOƒGƒ“?ƒJ?ƒ}ƒ“ kn-aut-sei=ƒOƒGƒ“? kn-aut-mei=ƒJ?ƒ}ƒ“ aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of General and Global Studies (GDP), Okayama University kn-affil=‰ªŽR‘åŠwŠwpŒ¤‹†‰@ ‹¤’Ê‹³ˆçEƒOƒ[ƒoƒ‹—̈æiGDPj affil-num=2 en-affil=Discovery Program for Global Learners, Okayama University kn-affil=‰ªŽR‘åŠwƒOƒ[ƒoƒ‹EƒfƒBƒXƒJƒoƒŠ[EƒvƒƒOƒ‰ƒ€ en-keyword=‘½•¶‰»‹¤C kn-keyword=‘½•¶‰»‹¤C en-keyword=‹¦“­ŠwK kn-keyword=‹¦“­ŠwK en-keyword=’T‹†Œ^ŠwK kn-keyword=’T‹†Œ^ŠwK en-keyword=ƒIƒ“ƒfƒ}ƒ“ƒhŒ^ƒIƒ“ƒ‰ƒCƒ“Žö‹Æ kn-keyword=ƒIƒ“ƒfƒ}ƒ“ƒhŒ^ƒIƒ“ƒ‰ƒCƒ“Žö‹Æ END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue= article-no= start-page=100 end-page=119 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Developing a Short-form Scale to Assess Learner Beliefs Regarding English Learning Strategies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Questionnaire surveys are a prevalent method in applied linguistics for investigating complex constructs, such as learner beliefs. However, their complex nature often creates overly lengthy instruments, making them impractical for classroom use or for obtaining timely educational insights. This study aimed to develop a simplified, yet robust version of an existing learner belief scale to address these challenges. The authors carefully selected 24 belief-specific items from an initial pool of 78 items from a previous study for use in an online survey, which was completed by 246 participants. The data were subject to exploratory factor analysis. This process resulted in a concise 12-item scale, could offer a more practical tool for language educators. en-copyright= kn-copyright= en-aut-name=MORITANIHiroshi en-aut-sei=MORITANI en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PUSINAAlexis en-aut-sei=PUSINA en-aut-mei=Alexis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Institute for Promotion of Education and Campus Life, Okayama University kn-affil= affil-num=2 en-affil=Institute for Promotion of Education and Campus Life, Okayama University kn-affil= en-keyword=Questionnaire items kn-keyword=Questionnaire items en-keyword=Learner beliefs kn-keyword=Learner beliefs en-keyword=Language learning strategies kn-keyword=Language learning strategies en-keyword=Exploratory factor analysis kn-keyword=Exploratory factor analysis END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue= article-no= start-page=91 end-page=99 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=To What Extent are Parents of High School Students with Developmental Disabilities Aware of Support for Students with Disabilities at Universities? kn-title=”­’BáŠQ‚ð—L‚·‚é‚Z¶‚Ì•ÛŒìŽÒ‚É‚æ‚éáŠQŠw¶Žx‰‡‚Ì”F’m“x en-subtitle= kn-subtitle= en-abstract=@This study aimed to investigate how well parents of high school students with developmental disabilities are aware of support for students with disabilities and student counseling at universities, how they obtained information about these services, and what kind of information dissemination do you expect from universities when seeking information about these services. The results revealed that parents are not sufficiently informed about university student support services. Parents are requesting the holding of information sessions and consultation meetings regarding student support. Furthermore, It is necessary to actively disseminate information to high school teachers and further promote high school-university collaboration initiatives. kn-abstract=@–{Œ¤‹†‚Å‚ÍC”­’BáŠQ‚ð—L‚·‚é‚Z¶‚Ì•ÛŒìŽÒ‚ªCu‘åŠw“™‚É‚¨‚¯‚éáŠQŠw¶Žx‰‡‚âŠw¶‘Š’k‚ð‚Ç‚Ì’ö“x’m‚Á‚Ä‚¢‚é‚©vCu‘åŠw“™‚É‚¨‚¯‚éáŠQŠw¶Žx‰‡‚âŠw¶‘Š’k‚Ìî•ñ‚ð‚ǂ̂悤‚É“üŽè‚µ‚½‚©vCu‘åŠw“™‚É‚¨‚¯‚éáŠQŠw¶Žx‰‡‚âŠw¶‘Š’k‚Ìî•ñŽûW‚ð‚·‚éã‚ÅC‘åŠw“™‚ɂǂ̂悤‚Èî•ñ”­M‚ðŠú‘Ò‚·‚é‚©v‚ɂ‚¢‚Ä’²¸‚ðs‚Á‚½B‚»‚ÌŒ‹‰ÊC‚Ü‚¾•ÛŒìŽÒ‚ɑ΂µC\•ª‚É‘åŠw‚ÌŠw¶Žx‰‡‚Ìî•ñ‚ªs‚«“Í‚¢‚Ä‚¢‚È‚¢‚±‚ÆCŠw¶Žx‰‡‚ÉŠÖ‚·‚éî•ñ”­M‚ðs‚¤à–¾‰ï‚â‘Š’k‰ï‚ðs‚¤‚±‚Æ‚ª•ÛŒìŽÒ‚©‚çŠú‘Ò‚³‚ê‚Ä‚¢‚邱‚ÆC”­’BáŠQ‚ð—L‚·‚é‚Z¶‚Ì‚‘åˆÚs‚ð‘£i‚·‚邽‚ß‚ÉC‚Z‚Ì涕û‚ɑ΂·‚éî•ñ”­M‚ท͓I‚És‚Á‚½‚èC‚‘å˜AŒg‚ÌŽæ‚è‘g‚Ý‚ð‚æ‚ès‚¤•K—v‚ª‚ ‚邱‚Æ“™‚ªŒ©o‚³‚ꂽB en-copyright= kn-copyright= en-aut-name=HARADAShin en-aut-sei=HARADA en-aut-mei=Shin kn-aut-name=Œ´“cV kn-aut-sei=Œ´“c kn-aut-mei=V aut-affil-num=1 ORCID= en-aut-name=IketaniKosuke en-aut-sei=Iketani en-aut-mei=Kosuke kn-aut-name=’r’Jq‰î kn-aut-sei=’r’J kn-aut-mei=q‰î aut-affil-num=2 ORCID= en-aut-name=MATSUIMegumi en-aut-sei=MATSUI en-aut-mei=Megumi kn-aut-name=¼ˆä‚ß‚®‚Ý kn-aut-sei=¼ˆä kn-aut-mei=‚ß‚®‚Ý aut-affil-num=3 ORCID= en-aut-name=MOCHIZUKINaoto en-aut-sei=MOCHIZUKI en-aut-mei=Naoto kn-aut-name=–]ŒŽ’¼l kn-aut-sei=–]ŒŽ kn-aut-mei=’¼l aut-affil-num=4 ORCID= affil-num=1 en-affil=General Education and Global Studies Field, Okayama University kn-affil=‰ªŽR‘åŠwŠwpŒ¤‹†‰@‹¤’Ê‹³ˆçEƒOƒ[ƒoƒ‹—̈æ affil-num=2 en-affil=General Education and Global Studies Field, Okayama University kn-affil=‰ªŽR‘åŠwŠwpŒ¤‹†‰@‹¤’Ê‹³ˆçEƒOƒ[ƒoƒ‹—̈æ affil-num=3 en-affil=General Education and Global Studies Field, Okayama University kn-affil=‰ªŽR‘åŠwŠwpŒ¤‹†‰@‹¤’Ê‹³ˆçEƒOƒ[ƒoƒ‹—̈æ affil-num=4 en-affil=Health and Counseling Center, The University of Osaka kn-affil=‘åã‘åŠwƒLƒƒƒ“ƒpƒXƒ‰ƒCƒtŒ’NŽx‰‡E‘Š’kƒZƒ“ƒ^[ en-keyword=áŠQŠw¶Žx‰‡ kn-keyword=áŠQŠw¶Žx‰‡ en-keyword=”­’BáŠQ‚ð—L‚·‚é‚Z¶‚Ì•ÛŒìŽÒ kn-keyword=”­’BáŠQ‚ð—L‚·‚é‚Z¶‚Ì•ÛŒìŽÒ en-keyword=‘ŠúŽx‰‡ kn-keyword=‘ŠúŽx‰‡ END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue= article-no= start-page=57 end-page=73 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Criteria for Faculty Decision-Making Regarding the Acceptance of International StudentsFFrom the perspective of faculty who accept many international students kn-title=—¯Šw¶Žó‚¯“ü‚ê‚É‚¨‚¯‚鋳ˆõ‚Ì”»’fŠî€ \‘½‚­‚Ì—¯Šw¶‚ðŽó‚¯“ü‚ê‚Ä‚¢‚鋳ˆõ‚ÌŽ‹“_‚©‚ç\ en-subtitle= kn-subtitle= en-abstract=@The declining birth rate significantly impacts domestic universities' enrolment, creating high expectations for increased international student intake. Within postgraduate education, however, a divide exists between faculty members who are and aren't proactive in accepting them. This study used semi-structured interviews to clarify the criteria faculty members use when accepting international students. The findings showed that while terminology varied, faculty commonly considered both gcharacterh and gabilityh. Furthermore, faculty who viewed international admissions positively had either studied or conducted research abroad and/or gained positive experiences from supervising their first international students. These factors fostered positive impressions and led to more proactive acceptance. kn-abstract=@­Žq‰»‚Í‘“à‘åŠw‚Ì’èˆõ[‘«—¦‚É[‚ȉe‹¿‚ð—^‚¦‚邱‚Æ‚©‚çA—¯Šw¶‚ÌŽó“ü‘‚ÉŠú‘Ò‚ªŠñ‚¹‚ç‚ê‚Ä‚¢‚éB‚µ‚©‚µA‘åŠw‰@‹³ˆç‚É‚¨‚¢‚Ä—¯Šw¶Žó“ü‚É‘OŒü‚«‚È‹³ˆõ‚ÆAÁ‹É“I‚È‹³ˆõ‚ªŒ©Žó‚¯‚ç‚ê‚éB–{Œ¤‹†‚Å‚ÍA‚æ‚葽‚­‚Ì—¯Šw¶‚ðŽó‚¯“ü‚ê‚Ä‚¢‚鋳ˆõ‚ªA‚ǂ̂悤‚È”»’fŠî€‚Ŏ󂯓ü‚ê‚ðŒˆ’è‚µ‚Ä‚¢‚é‚Ì‚©‚ðA”¼\‘¢‰»ƒCƒ“ƒ^ƒrƒ…[‚ð’Ê‚¶‚Ä–¾‚ç‚©‚É‚·‚邱‚Æ‚ðŽŽ‚Ý‚½B‚»‚ÌŒ‹‰ÊA”»’fŠî€‚ÉŠÖ‚µ‚Ä‚ÍA‹³ˆõ‚É‚æ‚è•\Œ»‚͈قȂ邪ul•¨v‚Æu”\—Ív‚ðŠm”F‚µ‚Ä‚¢‚邱‚Æ‚ª•ª‚©‚Á‚½B‚Ü‚½AŽó‚¯“ü‚ê‚ð‘OŒü‚«‚Él‚¦‚鋳ˆõ‚ÍA—¯ŠwEÝŠOŒ¤‹†ˆõŒoŒ±‚âA‰‚߂Ď󂯓ü‚ꂽ—¯Šw¶Žw“±‚ð’Ê‚¶‚Ä—Ç‚¢ŒoŒ±‚ð‚µ‚½‚±‚Æ“™‚ªA—¯Šw¶‚ɑ΂·‚éƒvƒ‰ƒX‚̈óÛ‚ð‚‚­‚èAÏ‹É“I‚Ȏ󂯓ü‚ê‚ɂ‚Ȃª‚Á‚Ä‚¢‚邱‚Æ‚ª–¾‚ç‚©‚É‚È‚Á‚½B en-copyright= kn-copyright= en-aut-name=INAMORITakao en-aut-sei=INAMORI en-aut-mei=Takao kn-aut-name=ˆîXŠx‰› kn-aut-sei=ˆîX kn-aut-mei=Šx‰› aut-affil-num=1 ORCID= affil-num=1 en-affil=Faculty of General and Global Studies, Okayama University kn-affil=ŠwpŒ¤‹†‰@‹¤’Ê‹³ˆçEƒOƒ[ƒoƒ‹—̈æ en-keyword=“ú–{—¯Šw kn-keyword=“ú–{—¯Šw en-keyword=‘åŠw‰@ kn-keyword=‘åŠw‰@ en-keyword=—¯Šw¶ kn-keyword=—¯Šw¶ en-keyword=Žó“ü‹³ˆõ kn-keyword=Žó“ü‹³ˆõ en-keyword=”»’fŠî€ kn-keyword=”»’fŠî€ END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue= article-no= start-page=41 end-page=56 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The Mediating Role of Self-Understanding in the Association Between Autistic Traits and Mental Health kn-title=Ž©•ÂƒXƒyƒNƒgƒ‰ƒ€Ç“Á«‚Ƹ_“IŒ’N‚ÌŠÖ˜AFŽ©ŒÈ—‰ð‚É‚æ‚é”}‰îŒø‰Ê‚ÌŒŸ“¢ en-subtitle= kn-subtitle= en-abstract=@This study examined whether positive and negative dimensions of self-understanding mediate the association between autistic traits and mental health in the general population. Analyzing cross-sectional data from 604 non-clinical Japanese adults, we found that higher autistic traits were significantly associated with poorer mental health. This association was partially mediated by the positive dimension of self-understanding, whereas the negative dimension did not mediate. Exploratory analyses suggested that this protective effect may be more pronounced in women than in men. These findings identify positive self-understanding as an actionable target for support and underscore the value of gender-informed approaches. kn-abstract= –{Œ¤‹†‚ÍAŽ©•ÂƒXƒyƒNƒgƒ‰ƒ€Ç“Á«‚Ƹ_“IŒ’N‚ÌŠÖ˜A‚É‚¨‚¢‚ÄAŽ©ŒÈ—‰ð‚ª‚ǂ̂悤‚È–ðŠ„‚ð‰Ê‚½‚·‚©‚𖾂炩‚É‚·‚邱‚Æ‚ð–Ú“I‚Æ‚µ‚½B“ú–{‚̬l604–¼‚̃f[ƒ^‚ð—˜—p‚µ‚½“ñŽŸ•ªÍ‚ÌŒ‹‰ÊAŽ©•ÂƒXƒyƒNƒgƒ‰ƒ€Ç“Á«‚Ì‚‚³‚Ƹ_“IŒ’N‚̈«‰»‚Æ‚ÌŠÔ‚É‚ÍŠÖ˜A‚ª”F‚ß‚ç‚ꂽB‚±‚ÌŠÖ˜A‚ÍAŽ©ŒÈ—‰ð‚Ìm’è“I‘¤–Ê‚É‚æ‚Á‚Ä•”•ª“I‚É”}‰î‚³‚ê‚邱‚Æ‚ªŽ¦‚³‚ꂽB“Á‚É‚±‚ÌŽ©ŒÈ—‰ð‚Ì•ÛŒì“I‚ÈŒø‰Ê‚ÍA’j«‚æ‚è‚à—«‚É‚¨‚¢‚Ä‚æ‚è‹­‚¢‰Â”\«‚ªŽ¦´‚³‚ꂽBˆê•û‚ÅAŽ©ŒÈ—‰ð‚̔ےè“I‘¤–Ê‚Í”}‰îŒø‰Ê‚ðŽ¦‚³‚È‚©‚Á‚½B‚±‚ê‚ç‚ÌŒ‹‰Ê‚©‚çAŽ©•ÂƒXƒyƒNƒgƒ‰ƒ€Ç“Á«‚ðŽ‚ÂlX‚Ö‚ÌŽx‰‡‚É‚¨‚¢‚ÄAm’è“I‚ÈŽ©ŒÈ—‰ð‚ð‘£i‚·‚邱‚Æ‚ªd—v‚Å‚ ‚èA«·‚ðl—¶‚µ‚½ƒAƒvƒ[ƒ`‚Ì•K—v«‚ªŽ¦´‚³‚ꂽB en-copyright= kn-copyright= en-aut-name=NISHIMURAHiroki en-aut-sei=NISHIMURA en-aut-mei=Hiroki kn-aut-name=¼‘º‘åŽ÷ kn-aut-sei=¼‘º kn-aut-mei=‘åŽ÷ aut-affil-num=1 ORCID= en-aut-name=UCHIDAAkihiro en-aut-sei=UCHIDA en-aut-mei=Akihiro kn-aut-name=“à“cW—T kn-aut-sei=“à“c kn-aut-mei=W—T aut-affil-num=2 ORCID= affil-num=1 en-affil=Institute for Promotion of Education and Campus Life, Okayama University kn-affil=‰ªŽR‘åŠw‹³ˆç„i‹@\ affil-num=2 en-affil=Okayama Psychiatric Medical Center kn-affil=’n•û“Æ—§s­–@l‰ªŽRŒ§¸_‰Èˆã—ÃZƒ“ƒ^[ en-keyword=Ž©•ÂƒXƒyƒNƒgƒ‰ƒ€Ç kn-keyword=Ž©•ÂƒXƒyƒNƒgƒ‰ƒ€Ç en-keyword=ƒƒ“ƒ^ƒ‹ƒwƒ‹ƒX kn-keyword=ƒƒ“ƒ^ƒ‹ƒwƒ‹ƒX en-keyword=¸_“IŒ’N kn-keyword=¸_“IŒ’N en-keyword=Ž©ŒÈ—‰ð kn-keyword=Ž©ŒÈ—‰ð en-keyword=«· kn-keyword=«· END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue= article-no= start-page=107048 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A cross-sectional study of the gut microbiota associated with urinary and serum equol production status in a general population of Japanese men en-subtitle= kn-subtitle= en-abstract= kn-abstract=Equol is a metabolite produced by the gut microbiota from the soy isoflavone daidzein. Previous studies identified bacteria capable of converting daidzein to equol. We investigated whether equol producers among Japanese with a high soy intake contained these bacteria. We also examined differences in equol production status between urine and serum and how the gut microbiota differs between these statuses. To minimize the potential confounding effects of hormonal variability in women, this cross-sectional study analyzed 853 Japanese men. Urinary and serum isoflavones were collected in the morning after fasting and were analyzed using LC-MS/MS. By applying a finite mixture model for each log10 equol/daidzein ratio, we defined equol producers and non-producers from urine and serum. Among 669 participants with fecal microbial measurements, the 16S rRNA gene was sequenced on a MiSeq System. The cut-off values for the log10 equol/daidzein ratio were ?0.94 for urine and ?0.95 for serum. Equol production status in urine and serum matched in 97 %, and equol producers from urine or serum were 42 %. The microbiota was more diverse in producers than in non-producers; the genus Senegalimassilia included strains with high sequence identity (>98 %) to daidzein reductase. The family Oscillospiraceae and class Clostridia also had approximately 46 %?48 % sequence identity. The equol production status of fasting urine and serum almost matched among a general population of Japanese men. Although we did not detect a microbiota with known daidzein reductase in equol producers, several shared similar sequences; these may include equol-producing bacteria that have not yet been identified. en-copyright= kn-copyright= en-aut-name=OkamiYukiko en-aut-sei=Okami en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ArimaHisatomi en-aut-sei=Arima en-aut-mei=Hisatomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BambaShigeki en-aut-sei=Bamba en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NamaiFu en-aut-sei=Namai en-aut-mei=Fu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoKeiko en-aut-sei=Kondo en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IdenoYuki en-aut-sei=Ideno en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SoejimaAyumi en-aut-sei=Soejima en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyakawaHaruna en-aut-sei=Miyakawa en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToriiSayuki en-aut-sei=Torii en-aut-mei=Sayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SegawaHiroyoshi en-aut-sei=Segawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhashiMizuki en-aut-sei=Ohashi en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawashimaMegumi en-aut-sei=Kawashima en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HisamatsuTakashi en-aut-sei=Hisamatsu en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KadotaAya en-aut-sei=Kadota en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SekikawaAkira en-aut-sei=Sekikawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiyoshiAkira en-aut-sei=Fujiyoshi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MiuraKatsuyuki en-aut-sei=Miura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SESSA Research Group en-aut-sei=SESSA Research Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=2 en-affil=Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University kn-affil= affil-num=3 en-affil=Department of Fundamental Nursing, Shiga University of Medical Science kn-affil= affil-num=4 en-affil=Graduate School of Agricultural Science, Tohoku University kn-affil= affil-num=5 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Gunma University Center for Food Science and Wellness kn-affil= affil-num=7 en-affil=Nutraceuticals Research Institute, R&D Headquarters, Nutraceuticals Division, Otsuka Pharmaceutical Co., Ltd. kn-affil= affil-num=8 en-affil=Nutraceuticals Research Institute, R&D Headquarters, Nutraceuticals Division, Otsuka Pharmaceutical Co., Ltd. kn-affil= affil-num=9 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=10 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=11 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=12 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=13 en-affil=Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=15 en-affil=Department of Epidemiology, School of Public Health, University of Pittsburgh kn-affil= affil-num=16 en-affil=Department of Hygiene, Wakayama Medical University kn-affil= affil-num=17 en-affil=NCD Epidemiology Research Center, Shiga University of Medical Science kn-affil= affil-num=18 en-affil= kn-affil= en-keyword=Equol kn-keyword=Equol en-keyword=Soy kn-keyword=Soy en-keyword=Isoflavone kn-keyword=Isoflavone en-keyword=Gut microbiota kn-keyword=Gut microbiota en-keyword=Men kn-keyword=Men en-keyword=Producers kn-keyword=Producers END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue= article-no= start-page=106742 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inscribed-type spherical speed reducer with uniform reduction ratio in all directions en-subtitle= kn-subtitle= en-abstract= kn-abstract=A spherical motor is an actuator that can generate rotational motion about all three orthogonal axes. However, it is difficult to obtain high output torque from most electromagnetic spherical motors, primarily due to limitations inherent in electromagnetic actuators, such as restricted magnetic force and thermal constraints. Since its torque cannot be increased using planar gears, spherical speed reducers that transmit rotational torque along three orthogonal axes through sphere-to-sphere contact are required. One major limitation of conventional spherical speed reducers is that their size increases significantly as the reduction ratio becomes higher. To address this issue, we propose a novel inscribed-type spherical speed reducer, in which the deceleration mechanism is integrated within the output sphere. This configuration enables a more compact design, reducing the overall size to approximately half that of conventional designs. To predict the angular velocity and transmitted torque, theoretical models for the rotation and torque transmission of the speed reducer were developed. According to the proposed model, the reduction ratio of the spherical speed reducer is 1/3. To verify the validity of these models, experiments were conducted to measure angular velocity and torque. The theoretical results agreed well with the experimental results. In addition, the theoretical torque exhibited an average relative error of 1.63 % compared to the experimental result. Therefore, it was confirmed that the rotation and torque transmission models were valid. These results demonstrate that a reduction ratio can be obtained in all directions of the 3-DOF of the spherical speed reducer, unlike conventional 1-DOF reducers. en-copyright= kn-copyright= en-aut-name=NaramuraSeiya en-aut-sei=Naramura en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TonegawaKoichi en-aut-sei=Tonegawa en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimookaSo en-aut-sei=Shimooka en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanoTomoaki en-aut-sei=Yano en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GofukuAkio en-aut-sei=Gofuku en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KasashimaNagayoshi en-aut-sei=Kasashima en-aut-mei=Nagayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamegawaTetsushi en-aut-sei=Kamegawa en-aut-mei=Tetsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Okayama Prefectural University kn-affil= affil-num=6 en-affil=National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=7 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Inscribed-type spherical speed reducer kn-keyword=Inscribed-type spherical speed reducer en-keyword=Rotation and torque transmission kn-keyword=Rotation and torque transmission en-keyword=Friction kn-keyword=Friction en-keyword=Spherical motor kn-keyword=Spherical motor en-keyword=Three-axis rotation kn-keyword=Three-axis rotation END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=57 end-page=66 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Piezo1-mediated mechanotransduction in cementocytes via protein kinase B and p38 mitogen-activated protein kinase signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/purpose: Cementocytes, terminally differentiated cells embedded within cellular cementum, are morphologically similar to osteocytes; however, their mechanosensory function remains poorly understood. This study aimed to investigate whether Piezo1, a mechanosensitive ion channel, contributes to the regulation of osteo/cementogenic gene expression in murine cementocyte-like IDG-CM6 cells.
Materials and methods: IDG-CM6 cells were subjected to cyclic stretch or treated with Piezo1-specific agonist Yoda1 or antagonist GsMTx4. Expression levels of osteo/cementogenic genes (Wnt1, Sost, Opg) and protein levels were analyzed. The involvement of intracellular signaling pathways was assessed using pharmacological inhibitors targeting mitogen-activated protein kinase and protein kinase B (PKB/AKT) pathways.
Results: Cyclic stretch upregulated Wnt1 and Opg, and downregulated Sost expression, without altering Piezo1 expression, suggesting an enhanced osteo/cementogenic potential. These effects were abolished by GsMTx4 and closely mimicked by Yoda1 stimulation. The Yoda1-induced gene expression changes were transient and diminished after withdrawal. Inhibitor experiments confirmed that Piezo1-mediated gene expression is modulated primarily through the AKT and p38 signaling pathways. Phosphorylation of AKT and p38 was rapidly induced by cyclic stretch.
Conclusion: Our findings demonstrate that Piezo1 functions as a mechanosensor in cementocytes, modulating the expression of osteo/cementogenic genes via the AKT and p38 pathways. This study provides new insight into the molecular mechanisms of cementocyte mechanotransduction and may inform strategies for periodontal regeneration and orthodontic treatment. en-copyright= kn-copyright= en-aut-name=XiongKaixin en-aut-sei=Xiong en-aut-mei=Kaixin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakisakaYukihiko en-aut-sei=Sakisaka en-aut-mei=Yukihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TenkumoTaichi en-aut-sei=Tenkumo en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NemotoEiji en-aut-sei=Nemoto en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MaruyamaKentaro en-aut-sei=Maruyama en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MuhammadFaisal en-aut-sei=Muhammad en-aut-mei=Faisal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzukiShigeki en-aut-sei=Suzuki en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TadaHiroyuki en-aut-sei=Tada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamadaSatoru en-aut-sei=Yamada en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Stomatology, Chengdu Integrated TCM and Western Medicine Hospital (Chengdu First Peoplefs Hospital) kn-affil= affil-num=2 en-affil=Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=3 en-affil=Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry kn-affil= affil-num=4 en-affil=Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=5 en-affil=Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=6 en-affil=Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=7 en-affil=Department of Operative Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Division of Oral Microbiology and Immunology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=9 en-affil=Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= en-keyword=Cementocytes kn-keyword=Cementocytes en-keyword=Mechanotransduction kn-keyword=Mechanotransduction en-keyword=Piezo1 kn-keyword=Piezo1 en-keyword=Signal transduction kn-keyword=Signal transduction END start-ver=1.4 cd-journal=joma no-vol=2026 cd-vols= no-issue=2 article-no= start-page=023F01 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feedback-Controlled Beam Pattern Measurement Method Using a Power-Variable Calibration Source for Cosmic Microwave Background Telescopes en-subtitle= kn-subtitle= en-abstract= kn-abstract=We demonstrate a novel beam pattern measurement method for the side lobe characterization of cosmic microwave background telescopes. The method employs a power-variable artificial microwave source under feedback control from the detector under test on the telescope. It enables us to extend the dynamic range of the beam pattern measurement without introducing nonlinearity effects from the detector. We conducted a laboratory-based proof-of-concept experiment, measuring the H-plane beam pattern of a horn antenna coupled to a diode detector at 81 GHz. We gained an additional dynamic range of 60.3 dB attributed to the feedback control. In addition, we verified the measurement by comparing it with other reference measurements obtained using conventional methods. The method is also applicable to general optical measurements requiring a high dynamic range to detect subtle nonidealities in the characteristics of optical devices. en-copyright= kn-copyright= en-aut-name=HiroseHaruaki en-aut-sei=Hirose en-aut-mei=Haruaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaMasaya en-aut-sei=Hasegawa en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanekoDaisuke en-aut-sei=Kaneko en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagasakiTaketo en-aut-sei=Nagasaki en-aut-mei=Taketo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakakuRyota en-aut-sei=Takaku en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=de?HaanTijmen en-aut-sei=de?Haan en-aut-mei=Tijmen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakakuraSatoru en-aut-sei=Takakura en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujinoTakuro en-aut-sei=Fujino en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Physics, Graduate School of Engineering Science, Yokohama National University kn-affil= affil-num=2 en-affil=Institute of Particle and Nuclear Studies (IPNS), High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=3 en-affil=International Center for Quantum-field Measurement Systems for Studies of the Universe and Particles (WPI-QUP), High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=4 en-affil=Accelerator Laboratory (ACCL), High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Institute of Particle and Nuclear Studies (IPNS), High Energy Accelerator Research Organization (KEK) kn-affil= affil-num=7 en-affil=Department of Physics, Faculty of Science, The University of Tokyo kn-affil= affil-num=8 en-affil=International Center for Quantum-field Measurement Systems for Studies of the Universe and Particles (WPI-QUP), High Energy Accelerator Research Organization (KEK) kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=11 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of Wet-Bulb Globe Temperature with heat-related illness hospitalizations in Japan: a time-stratified, case-crossover study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Heat-related illnesses are a serious public health concern and are exacerbated by global warming. Wet-Bulb Globe Temperature (WBGT) is widely used as a heat stress indicator, but its clinical impact remains unclear. This study aimed to investigate the association between hourly variations in WBGT and the incidence of hospitalizations for heat-related illness in Japan using a nationwide database. By incorporating individual-level clinical data and performing stratified analyses, we sought to provide a more granular understanding of how heat exposure affects the risk of heat-related illness requiring hospitalization.
Methods We conducted a time-stratified, case-crossover study using data collected from July to September in 2020 and 2021 in the Heatstroke STUDY registry. The inclusion criteria were patients registered in the Heatstroke STUDY registry, specifically hospitalized patients with heat-related illness who were transported to participating hospitals during the study period. Hourly WBGT values were assigned based on the nearest monitoring station to each hospital. Conditional logistic regression and distributed lag models were used to estimate associations between WBGT and the risk of hospitalization.
Results A total of 1,653 heat-related illness hospitalizations were analyzed. The mean patient age was 67.9 years; 67.6% were male. Each 1 ‹C increase in WBGT at onset (hospital arrival) was associated with a significantly increased risk of hospitalization (OR 1.10, 95% CI: 1.05?1.15). The cumulative effect over the prior six hours was also significant (OR 1.56, 95% CI: 1.50?1.62). Compared with WBGT? Conclusions Higher WBGT levels were associated with an increased risk of heat-related hospitalization. Although the effect appeared greater in some subgroups, only patients with mental disorders demonstrated statistically significant effect modification, suggesting elevated WBGT confers risk broadly. en-copyright= kn-copyright= en-aut-name=YamamuraYuka en-aut-sei=Yamamura en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HongoTakashi en-aut-sei=Hongo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasaiFumiya en-aut-sei=Sasai en-aut-mei=Fumiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokiokaKohei en-aut-sei=Tokioka en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KandaJun en-aut-sei=Kanda en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YokoboriShoji en-aut-sei=Yokobori en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Emergency and Critical Care Medicine, Nippon Medical School Musashikosugi Hospital kn-affil= affil-num=9 en-affil=Department of Emergency and Critical Care Medicine, Nippon Medical School kn-affil= affil-num=10 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Wet-Bulb Globe Temperature kn-keyword=Wet-Bulb Globe Temperature en-keyword=Heat stroke kn-keyword=Heat stroke en-keyword=Heat related illness kn-keyword=Heat related illness en-keyword=Global warming kn-keyword=Global warming END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=11 article-no= start-page=e97962 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association of Carboxyhemoglobin With Severity and Outcomes in Hypothermic Patients: A Retrospective Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction
Carboxyhemoglobin (COHb), an endogenous marker of carbon monoxide production mediated by heme oxygenase-1, may reflect physiological stress responses in critically ill patients. However, its clinical relevance in accidental hypothermia remains unclear.

Methods
We conducted a single-center retrospective cohort study of adult patients admitted to the emergency ICU with accidental hypothermia between January 1, 2019, and March 31, 2025. Patients were categorized into low- and high-COHb groups based on median COHb levels upon emergency department arrival. Associations between COHb levels, disease severity (Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores), and 28-day mortality were analyzed using regression models adjusted for clinical confounders.

Results
Among the 88 patients, who had a median admission temperature of 28.7‹C, 45 were classified into the low-COHb group and 43 into the high-COHb group, based on a median COHb level of 0.3%. Lower COHb levels on admission were significantly associated with higher APACHE II scores (ƒÀ = ?4.20; 95% CI, ?7.56 to ?0.85), but not with SOFA scores. Admission and minimum COHb levels were not associated with 28-day mortality. However, higher maximum COHb levels within the first 24 hours were independently associated with lower 28-day mortality (adjusted OR, 0.17; 95% CI, 0.023 to 0.93).

Conclusions
Lower COHb levels were associated with greater disease severity, and higher maximum COHb levels were associated with lower 28-day mortality. COHb may reflect systemic stress in accidental hypothermia, but its prognostic value appears limited. en-copyright= kn-copyright= en-aut-name=MiyoshiYuya en-aut-sei=Miyoshi en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=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=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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= 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= en-keyword=carbon monoxide kn-keyword=carbon monoxide en-keyword=carboxyhemoglobin kn-keyword=carboxyhemoglobin en-keyword=heme oxygenase kn-keyword=heme oxygenase en-keyword=hypothermia kn-keyword=hypothermia en-keyword=sepsis kn-keyword=sepsis END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=5 article-no= start-page=372 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alpha-Ketoglutarate Drives an Osteogenic and Extracellular Matrix Gene Program in Periodontal Ligament Fibroblasts via Selective Reduction of H3K27me3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontal disease damages the tissues that support teeth and can ultimately lead to tooth loss, yet effective treatments to regenerate these tissues are still limited. Recent studies have shown that substances produced during normal cellular metabolism can influence how genes are regulated, but their role in periodontal regeneration has not been fully clarified. In this study, we investigated whether alpha-ketoglutarate, a naturally occurring metabolite involved in energy production, could promote periodontal tissue regeneration. We found that alpha-ketoglutarate enhanced bone-related and extracellular matrix-related gene expression in human periodontal ligament cells by reducing a repressive gene-regulatory signal that normally suppresses these genes. Importantly, alpha-ketoglutarate did not broadly alter chromatin accessibility, indicating that its effects were mediated through selective gene regulation. Furthermore, oral administration of alpha-ketoglutarate promoted alveolar bone regeneration and collagen-rich tissue formation in a mouse model of periodontal disease. Because alpha-ketoglutarate is a naturally occurring molecule in the body, these findings suggest that metabolite-based regulation of gene activity may represent a promising and safe approach for periodontal tissue regeneration. en-copyright= kn-copyright= en-aut-name=HasegawaRyu en-aut-sei=Hasegawa en-aut-mei=Ryu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiShigeki en-aut-sei=Suzuki en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FahrezaRahmad Rifqi en-aut-sei=Fahreza en-aut-mei=Rahmad Rifqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsaiShin-Ho en-aut-sei=Tsai en-aut-mei=Shin-Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DaidoujiYoshino en-aut-sei=Daidouji en-aut-mei=Yoshino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriMasato en-aut-sei=Omori en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KajikawaTetsuhiro en-aut-sei=Kajikawa en-aut-mei=Tetsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamadaSatoru en-aut-sei=Yamada en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=2 en-affil=Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=4 en-affil=Department of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=6 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=7 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= affil-num=8 en-affil=Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry kn-affil= en-keyword=alpha-ketoglutarate kn-keyword=alpha-ketoglutarate en-keyword=periodontal ligament kn-keyword=periodontal ligament en-keyword=extracellular matrix kn-keyword=extracellular matrix en-keyword=epigenetic regulation kn-keyword=epigenetic regulation en-keyword=H3K27me3 kn-keyword=H3K27me3 END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=4 article-no= start-page=715 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Antigen Remodeling in Colorectal Cancer: How Radiotherapy and Chemotherapy Enhance Immunotherapy Responsiveness en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colorectal cancer (CRC) is traditionally considered a gcold tumorh characterized by low immunogenicity and limited responsiveness to immune checkpoint inhibitors (ICIs). However, recent findings reveal that cytotoxic modalities can reprogram this immunologically inert landscape. This review integrates these evolving concepts to guide the optimization of future treatments. Radiotherapy induces extensive DNA double-strand breaks, which may generate de novo mutations through error-prone repair while simultaneously exposing cryptic antigens via increased transcriptional instability, alternative splicing, and enhanced proteasomal processing. Chemoradiation also amplifies epigenetic and epitranscriptomic sources of neoepitope diversity, including RNA editing and stress-induced splicing alterations, expanding the immunopeptidome beyond canonical mutation-driven neoantigens. These changes collectively enhance antigen presentation and facilitate T-cell priming. Chemotherapy further reduces immunosuppressive cell populations and promotes dendritic cell activation, creating a permissive milieu for subsequent immune engagement. Clinically, the VOLTAGE studies demonstrated that long-course chemoradiotherapy can sensitize even mismatch repair?proficient rectal cancers to PD-1 blockade, yielding clinically meaningful pathological responses. In contrast, mismatch repair?deficient rectal tumors may respond completely to ICIs alone. Short-course radiotherapy combined with chemotherapy and ICIs has also shown encouraging activity in the setting of total neoadjuvant therapy. Collectively, these findings support a paradigm in which radiotherapy, chemotherapy, and epigenetic/epitranscriptomic alterations?including RNA editing?act as potent modulators of tumor antigenicity. By expanding the neoantigen repertoire and reshaping the tumor microenvironment, these strategies can transform CRC from a cold tumor into one that is increasingly responsive to immunotherapy. en-copyright= kn-copyright= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriwakeKazuya en-aut-sei=Moriwake en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KayanoMasashi en-aut-sei=Kayano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=immunotherapy kn-keyword=immunotherapy en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=neoantigens kn-keyword=neoantigens 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=2026 dt-pub=20260221 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Turning pancreatic cancer from cold to hot: the promise of a p53-expressing oncolytic adenovirus (OBP-702) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic cancer remains one of the most lethal malignancies, with limited therapeutic options and poor responsiveness to immune checkpoint inhibitors (ICIs). This resistance is largely attributed to its profoundly immunosuppressive and desmoplastic tumor microenvironment (TME), characterized by low tumor mutational burden, dense stroma, and abundant immunosuppressive cell populations. Therefore, strategies capable of enhancing tumor immunogenicity and overcoming immune evasion are urgently needed. Oncolytic virotherapy is a promising approach, offering not only tumor-selective cytotoxicity, but also potent immunomodulatory effects. Of these agents, Telomelysin (OBP-301, Suratadenoturev), a telomerase-specific oncolytic adenovirus, demonstrated clinical safety but limited efficacy in refractory tumors. To address this challenge, we developed OBP-702, a next-generation, p53-armed, oncolytic adenovirus designed to augment antitumor activity. Preclinical studies have shown that OBP-702 exerts robust cytotoxicity through multiple mechanisms, including p53-mediated apoptosis and autophagy, E1A?E2F1-mediated p21 suppression, and inhibition of oncogenic KRAS pathways. Importantly, OBP-702 induces strong immunogenic cell death, activates dendritic cells, and promotes tumor-specific T-cell responses, effectively converting immunologically gcoldh pancreatic tumors into ghoth tumors. OBP-702 also remodels the immunosuppressive TME by reducing granulocyte?macrophage colony-stimulating factor (GM-CSF) secretion, suppressing myeloid-derived suppressor cells (MDSCs), and targeting stromal components, such as cancer-associated fibroblasts (CAFs). These effects contribute to enhanced responses to ICIs and standard chemotherapies. Given its multifaceted antitumor functions and ability to overcome key barriers in pancreatic cancer, OBP-702 represents a highly promising therapeutic candidate. A first-in-human clinical trial evaluating endoscopic ultrasonography-guided intratumoral injection of OBP-702 is currently in preparation, expected to advance clinical translation of this novel virotherapeutic strategy. en-copyright= kn-copyright= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=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=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= 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=Center for Innovative Clinical Medicine, Okayama University Hospital 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=Oncolys BioPharma Inc kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Oncolytic adenovirus kn-keyword=Oncolytic adenovirus en-keyword=p53 kn-keyword=p53 en-keyword=OBP-702 kn-keyword=OBP-702 en-keyword=Immunogenic cell death kn-keyword=Immunogenic cell death en-keyword=Tumor microenvironment kn-keyword=Tumor microenvironment en-keyword=Pancreatic cancer kn-keyword=Pancreatic cancer END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=275 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Study on the Development of an Image Classification System for Urban Sprawl Areas in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=In Japan, unlike in many other countries, urbanization has progressed while original rural road structures have been retained, leading to distinctive urban sprawl areas with intermingling residential lots and farmland. Currently, much of Japanfs urban areas consist of urban sprawl areas, posing considerable challenges for infrastructure development. However, for such urban sprawl areas in Japan, it is difficult to say that methods have been established to identify their spatial distribution based on quantitative evaluation. Therefore, for this study, we used machine learning to investigate a system that extracts sprawling urban areas from aerial photographs divided into meshes. In the systemfs design, we prioritized precision to ensure the reliable detection of urban sprawl areas. Consequently, the accuracy of identifying sprawl areas achieved precision of 0.81, recall of 0.63, and an F-score of 0.71. Examination of the classification results of sprawl areas revealed that most misclassifications occurred near class boundaries. By contrast, areas with particularly high levels of urban sprawl showed few misclassifications. en-copyright= kn-copyright= en-aut-name=HemmiRyota en-aut-sei=Hemmi en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UjiharaTakehito en-aut-sei=Ujihara en-aut-mei=Takehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AndoRyosuke en-aut-sei=Ando en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoSeiji en-aut-sei=Hashimoto en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=National Institute for Land and Infrastructure Management, Ministry of Land, Infrastructure Transport and Tourism kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=image classification kn-keyword=image classification en-keyword=machine learning kn-keyword=machine learning en-keyword=sprawl kn-keyword=sprawl END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=96 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260109 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of an oral exercise intervention on pre-frailty or frailty in older people: a randomized clinical trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Frailty is often experienced by older adults, which can lead to long-term health problems. We aimed to examine associations with improvements in nutritional status, sarcopenia (age-related loss of skeletal muscle mass and strength), and frailty in four groups with different oral exercise frequencies.
Methods: We conducted a prospective, parallel multi-arm randomized controlled trial (Japan Registry of Clinical Trials (jRCT) 1062210063) to test the effects of oral exercise on frailty in older adults. Each intervention consisted of a standardized oral exercise protocol including neck exercises, lip exercises, and tongue movements, designed to improve oral function and reduce frailty. The primary outcome was the change in the number of frailty criteria from baseline to follow-up. Individuals aged ?60 years were screened for frailty status using standardized criteria at the Department of Preventive Dentistry at Okayama University Hospital between October 2022 and December 2023. Those identified as pre-frailty or frailty were eligible and enrolled in the study. After screening 60 individuals, 58 eligible participants were randomly assigned using block randomization to one of four oral exercise frequency groups: 3 times/day & everyday, 3 times/day & 3 days/week, once/day & everyday, and once/day & 3 days/week. A two-way repeated measures analysis of variance was used to evaluate the impact of the four frequencies of oral exercise methods on frailty in older adults. Outcome assessors were blinded; participants were not.
Results: Here we show the results of the 58 participants. Group sizes are: 3 times/day & everyday (n?=?14), 3 times/day & 3 days/week (n?=?15), once/day & everyday (n?=?14), once/day & 3 days/week (n?=?15). The trial is completed as planned, and all randomized participants are analyzed. The main effect of time is significant for the number of frailty criteria (F?=?14.803, p? Conclusions: After conducting oral exercises for 3 months on older adults with pre-frailty or frailty, improvements in frailty are observed. Overall, these exercises could be a simple, low-cost way to support healthy aging in the community. en-copyright= kn-copyright= en-aut-name=TakeuchiNoriko en-aut-sei=Takeuchi en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawadaNanami en-aut-sei=Sawada en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InadaSakura en-aut-sei=Inada en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EkuniDaisuke en-aut-sei=Ekuni en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University kn-affil= affil-num=2 en-affil=Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University kn-affil= affil-num=3 en-affil=Division of Health Promotion, Okayama-City Health Center kn-affil= affil-num=4 en-affil=Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care kn-affil= affil-num=5 en-affil=Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=164 cd-vols= no-issue= article-no= start-page=108315 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Global trends in Clostridioides difficile infection?related mortality, 2001-2023: An observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Clostridioides difficile infection (CDI) is a major public health concern, particularly in aging populations. The aim of this study was to evaluate global trends in CDI-related mortality to inform sustainable and cost-effective management strategies.
Methods: We conducted an observational study using mortality data from the World Health Organization (WHO) database spanning 2001 to 2023. Sixty-three countries with satisfactory data quality and at least 12 years of data between 2001 and 2023 were included. Crude and age-standardized CDI-related mortality rates per 1,000,000 individuals were calculated after stratification by age, sex, WHO region, and sociodemographic index (SDI). Global trends were analyzed using locally weighted regression.
Results: The global age-standardized CDI-related mortality rate was 0.76 per 1,000,000 individuals in 2001, peaked at 4.08 in 2010, and declined to 2.44 in 2023. The most notable downward trends were observed in the Americas and high-SDI countries. These improvements may reflect the impact of multidisciplinary efforts in CDI prevention and management.
Conclusions: Although CDI-related mortality has declined globally over the past decade, the disease remains a significant threat, especially in older populations. Ongoing global efforts are essential to further reduce CDI-related deaths. 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=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaKo en-aut-sei=Harada en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoMaki en-aut-sei=Yamamoto en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=VuQuynh Thi en-aut-sei=Vu en-aut-mei=Quynh Thi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BelangoyKeith Pardillada en-aut-sei=Belangoy en-aut-mei=Keith Pardillada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OuddoudHanane en-aut-sei=Ouddoud en-aut-mei=Hanane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Hematology/Oncology, Mayo Clinic kn-affil= affil-num=3 en-affil=Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=4 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Aging kn-keyword=Aging en-keyword=Locally weighted regression model kn-keyword=Locally weighted regression model en-keyword=Infection kn-keyword=Infection en-keyword=Clostridioides difficile kn-keyword=Clostridioides difficile en-keyword=Disparity kn-keyword=Disparity END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=e100872 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Saliva as a Reliable and Non-invasive Sample for Detecting Influenza A in Severe Acute Respiratory Infection Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Nasopharyngeal swab sampling remains the gold standard for influenza diagnosis; however, it has several limitations, including dependence on medical staff, invasiveness, potential for nosocomial transmission, and occupational exposure risk. Non-invasive alternatives, such as saliva and nasal vestibular swabs, may improve patient comfort and participation in clinical studies. In addition, diagnosis with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) is often delayed because it requires trained laboratory technicians and facilities with appropriate laboratory settings. Although rapid diagnostic devices such as the GenPad? offer potential alternatives to RT-qPCR, their performance with non-invasive samples remains insufficiently explored. This study addresses the two key questions for influenza detection in severe acute respiratory infection (SARI) cases: (i) whether saliva or nasal vestibular swab samples serve as suitable alternatives to nasopharyngeal swab samples, and (ii) whether the GenPad? provides a reliable option for detecting influenza using saliva samples.
Methodology
A prospective observational study was conducted with 16 inpatients classified as having SARIs and diagnosed with influenza between December 2024 and March 2025 in Japan. Paired saliva and nasal vestibular swab samples were collected 1-9 (median = 3.5) days after symptom onset. RT-qPCR testing was performed according to the National Institute of Infectious Diseases protocol. Saliva samples were also tested using the GenPad? system. Comparisons between sample types and diagnostic methods were analyzed using the exact McNemar's test.
Results
Among the 16 influenza-positive patients, saliva samples demonstrated higher sensitivity (87.5%) than nasal vestibular swabs (31.3%) in RT-qPCR when compared with the diagnostic results obtained from nasopharyngeal swabs. A comparison of RT-qPCR results between saliva and nasal vestibular swabs revealed a total agreement of 43.8%, with exact McNemar's test showing a significant difference (p = 0.0039). While nasal vestibular swabs showed inconsistent results, saliva samples consistently tested positive, particularly within seven days of symptom onset (100% positive agreement). The GenPad?, a rapid diagnostic device, showed promising performance (92.9%) using saliva samples compared to RT-qPCR.
Conclusions
Saliva is a reliable non-invasive alternative to nasopharyngeal swabs for influenza detection in SARI cases, particularly within seven days of symptom onset, whereas nasal vestibular swabs show lower sensitivity. Additionally, the GenPad? provides comparable performance to RT-qPCR using saliva samples, offering a rapid, portable diagnostic option. These approaches may mitigate discomfort, minimize infection risk for healthcare workers, and improve testing capacity. However, the absence of influenza-negative controls and the small sample size (n = 16) substantially limit the assessment of diagnostic accuracy and specificity. As a result, the broader applicability of our findings should be interpreted with caution, and further studies are required to validate these observations. en-copyright= kn-copyright= en-aut-name=TakeuchiJunko S en-aut-sei=Takeuchi en-aut-mei=Junko S kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsunagaNobuaki en-aut-sei=Matsunaga en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukadaAi en-aut-sei=Tsukada en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwamotoNoriko en-aut-sei=Iwamoto en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FuwaNoriko en-aut-sei=Fuwa en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IchikawaTakahiro en-aut-sei=Ichikawa en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatoYasuyuki en-aut-sei=Kato en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TomitaYuka en-aut-sei=Tomita en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitagawaHiroki en-aut-sei=Kitagawa en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamatoMasaya en-aut-sei=Yamato en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AoyagiTetsuji en-aut-sei=Aoyagi en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=HaseRyota en-aut-sei=Hase en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HatakeyamaShuji en-aut-sei=Hatakeyama en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=InabaTohru en-aut-sei=Inaba en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IzumikawaKoichi en-aut-sei=Izumikawa en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakesueYoshio en-aut-sei=Takesue en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KimuraMoto en-aut-sei=Kimura en-aut-mei=Moto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OhmagariNorio en-aut-sei=Ohmagari en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=2 en-affil=Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security kn-affil= affil-num=3 en-affil=Antimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health Security kn-affil= affil-num=4 en-affil=Disease Control and Prevention Center, Japan Institute for Health Security kn-affil= affil-num=5 en-affil=Disease Control and Prevention Center, Japan Institute for Health Security kn-affil= affil-num=6 en-affil=Department of Infectious Diseases, Sapporo City General Hospital kn-affil= affil-num=7 en-affil=Department of Infectious Diseases, International University of Health and Welfare (IUHW) Narita Hospital kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Hiroshima University Hospital kn-affil= affil-num=10 en-affil=Department of General Internal Medicine and Infectious Diseases, Rinku General Medical Center kn-affil= affil-num=11 en-affil=Department of Clinical Infectious Diseases, Tohoku University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Infectious Diseases, Japanese Red Cross Narita Hospital kn-affil= affil-num=14 en-affil=Division of Infectious Diseases, Jichi Medical University Hospital kn-affil= affil-num=15 en-affil=Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine kn-affil= affil-num=16 en-affil= kn-affil= affil-num=17 en-affil=Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=18 en-affil=Department of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health Security kn-affil= affil-num=19 en-affil=Disease Control and Prevention Center, Japan Institute for Health Security kn-affil= en-keyword=influenza a kn-keyword=influenza a en-keyword=nasal vestibular swab kn-keyword=nasal vestibular swab en-keyword=nasopharyngeal swab kn-keyword=nasopharyngeal swab en-keyword=rapid diagnostics kn-keyword=rapid diagnostics en-keyword=rt-qpcr kn-keyword=rt-qpcr en-keyword=saliva kn-keyword=saliva en-keyword=sari kn-keyword=sari END start-ver=1.4 cd-journal=joma no-vol=112 cd-vols= no-issue=2 article-no= start-page=2301 end-page=2310 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although total thymectomy has been the standard surgical approach for thymic epithelial tumors, an increasing number of recent reports suggest that partial thymectomy for early-stage thymomas may yield outcomes comparable to those of total thymectomy. However, whether partial thymectomy is a viable alternative for thymic carcinoma remains unclear.
Materials and methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan?Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors.
Results: Among patients with clinical stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (P = 0.0027) and higher recurrence risk (P < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group.
Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence. en-copyright= kn-copyright= en-aut-name=HayashiTatsuya en-aut-sei=Hayashi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OtsukaTomoaki en-aut-sei=Otsuka en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KurosakiTakeshi en-aut-sei=Kurosaki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamadaEiji en-aut-sei=Yamada en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsudaEisuke en-aut-sei=Matsuda en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HayashiTatsurou en-aut-sei=Hayashi en-aut-mei=Tatsurou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HayamaMakio en-aut-sei=Hayama en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TaoHiroyuki en-aut-sei=Tao en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HiramiYuji en-aut-sei=Hirami en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=WashioKazuhiro en-aut-sei=Washio en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MisaoTakahiko en-aut-sei=Misao en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=SanoYoshifumi en-aut-sei=Sano en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KawamataOsamu en-aut-sei=Kawamata en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Center of Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=9 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=10 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=11 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=12 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=13 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=14 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=15 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=16 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=17 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=18 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=19 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=20 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=21 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=22 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=23 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=24 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=25 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=26 en-affil=Okayama University Thoracic Surgery Study Group (OUTSSG) kn-affil= affil-num=27 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=partial thymectomy kn-keyword=partial thymectomy en-keyword=real-world data analysis kn-keyword=real-world data analysis en-keyword=retrospective comparative cohort study kn-keyword=retrospective comparative cohort study en-keyword=thymic carcinoma kn-keyword=thymic carcinoma en-keyword=thymic epithelial tumors kn-keyword=thymic epithelial tumors en-keyword=total thymectomy kn-keyword=total thymectomy 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=2026 dt-pub=20260219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induction of IL-9-producing CD8+ T cells by ascochlorin derivatives en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Purpose: Ascochlorin (ASC) is an antiviral antibiotic from the fermented broth of Ascochyta viciae which exerts an inhibitory effect to cancers. Its impact on immune cells has not been examined. In this study, we obtained ASC derivatives with less cytotoxicity and determined whether they affected T cells, indicating possible immune-mediated antitumour effects.
Experimental Approach: Newly synthesised ASC derivatives were screened for inhibitory effects on T-cell antigen receptor (TCR)-stimulated proliferative responses using murine CD4+ and CD8+ T cells. Two compounds were identified that exhibited >10-fold less toxicity compared with ASC. N184, the less toxic of the two, was analysed for its in vivo antitumour effects, and in vitro effects on CD8+ T-cell proliferation, survival, cytokine production and exhaustion, using microscopy, qPCR and flow cytometry.
Key Results: N184 induced limited IL-9 production in CD8+ T cells following TCR stimulation, thereby improving cell survival. It also enhanced cytokine production in the late phase of proliferation and suppressed the induction of exhaustion. N184 suppressed tumour growth in mice in a CD8+ T cell-dependent manner. The effect was partially prevented by an IL-9-neutralising antibody.
Conclusion and Implications: N184 induces differentiation of IL-9-producing CD8+ T cells in vitro and elicits antitumour immunity in an IL-9-dependent manner. en-copyright= kn-copyright= en-aut-name=ImanoNatsumi en-aut-sei=Imano en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishidaMikako en-aut-sei=Nishida en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokumasuMiho en-aut-sei=Tokumasu en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhaoWeiyang en-aut-sei=Zhao en-aut-mei=Weiyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamashitaNahoko en-aut-sei=Yamashita en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Immunology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=ascochlorin derivative kn-keyword=ascochlorin derivative en-keyword=CD8 positive T lymphocytes kn-keyword=CD8 positive T lymphocytes en-keyword=cell survival kn-keyword=cell survival en-keyword=IFN-ƒÁ kn-keyword=IFN-ƒÁ en-keyword=interleukin-9 kn-keyword=interleukin-9 en-keyword=Tc9 kn-keyword=Tc9 en-keyword=tumour immunity kn-keyword=tumour immunity END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue= article-no= start-page=1673581 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Binding of IgA1 and surface-expressed collagen-binding protein of Streptococcus mutans contributes to IgA nephropathy pathogenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The present study was conducted to examine the interaction between collagen-binding protein (Cnm) of Streptococcus mutans and immunoglobulin (IgA) to clarify the possible involvement in IgA nephropathy (IgAN) development.
Methods: The binding of Cnm to human immunoglobulins was examined using an enzyme-linked immunosorbent assay. A nephritis-induced rat model was employed to confirm the localization of Cnm.
Results: IgA1 showed significantly greater binding ability to Cnm than to other bacterial surface proteins, and Cnm showed significantly greater binding ability to IgA1 than to other immunoglobulins. In rats administered Cnm, IgA deposition was observed in the glomerular mesangial region. Furthermore, biotin-labeled Cnm was observed in the same region as IgA deposition in the Cnm group.
Conclusions: Taken together, it is considered that following invasion into the bloodstream, Cnm binds to and forms a complex with IgA1, leading to deposition of IgA1 in renal glomeruli. en-copyright= kn-copyright= en-aut-name=MatsuokaDaiki en-aut-sei=Matsuoka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SueharaKana en-aut-sei=Suehara en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakaShuhei en-aut-sei=Naka en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MisakiTaro en-aut-sei=Misaki en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagasawaYasuyuki en-aut-sei=Nagasawa en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoSeigo en-aut-sei=Ito en-aut-mei=Seigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuehiroYuto en-aut-sei=Suehiro en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NomuraRyota en-aut-sei=Nomura en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoKazuhiko en-aut-sei=Nakano en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Matsumoto-NakanoMichiyo en-aut-sei=Matsumoto-Nakano en-aut-mei=Michiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Nephrology, Seirei Hamamatsu General Hospital kn-affil= affil-num=5 en-affil=Department of General Internal Medicine, Hyogo Medical University kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Japan Self-Defense Force Iruma Hospital kn-affil= affil-num=7 en-affil=Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka kn-affil= affil-num=8 en-affil=Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=9 en-affil=Department of Pediatric Dentistry, Graduate School of Dentistry, The University of Osaka kn-affil= affil-num=10 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=bacterial surface proteins kn-keyword=bacterial surface proteins en-keyword=collagen-binding protein kn-keyword=collagen-binding protein en-keyword=human immunoglobulins kn-keyword=human immunoglobulins en-keyword=IgA nephropathy kn-keyword=IgA nephropathy en-keyword=Streptococcus mutans kn-keyword=Streptococcus mutans END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=4 article-no= start-page=1081 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Generative AI?Based Technical Data Extraction Tool for IoT Application Systems en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, Internet of Things (IoT) application systems play an essential role in smart cities, industry, healthcare, agriculture, and smart homes. For non-expert users, designing and implementing IoT application systems remains challenging, especially when configuring sensors, edge devices, and server platforms. To support configuration tasks of IoT application systems, we have developed an AI-based setup assistance tool. However, AI models still fail to reliably support newly released or previously unseen devices, sometimes producing incomplete or erroneous outputs that may lead to configuration failures. Incorporating their technical-document information into Retrieval-Augmented Generation (RAG) is an effective way to supplement AI knowledge and improve reliability. In this paper, we propose a generative AI-based technical data extraction tool to address the challenges. It extracts essential technical information using the schema-based extraction from given PDF or HTML datasheets and converts it into a structured format suitable for AI-supported configurations. A local vector database is used to enable semantic similarity retrieval and provide document-grounded evidence for RAG-based answering, ensuring consistent support for previously unseen IoT devices. For evaluations, we applied the proposal to several sensor and device datasheets and compared extracted specifications with ground-truth values to measure accuracy and completeness. Then, we compared end-to-end configuration QA reliability against a commercial baseline (ChatPDF) using the golden benchmark. The results show that the proposed tool reliably acquires key specifications and significantly improves end-to-end configuration QA reliability. Across 960 golden QA pairs, the proposed method improves Recall from 0.636 to 0.926 and Accuracy from 0.595 to 0.807 compared with ChatPDF. en-copyright= kn-copyright= en-aut-name=KongDezheng en-aut-sei=Kong en-aut-mei=Dezheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KyawHtoo Htoo Sandi en-aut-sei=Kyaw en-aut-mei=Htoo Htoo Sandi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KotamaI Nyoman Darma en-aut-sei=Kotama en-aut-mei=I Nyoman Darma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhuZihao en-aut-sei=Zhu en-aut-mei=Zihao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RahmadaniAlfiandi Aulia en-aut-sei=Rahmadani en-aut-mei=Alfiandi Aulia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= en-keyword=internet of things kn-keyword=internet of things en-keyword=AI kn-keyword=AI en-keyword=retrieval-augmented generation kn-keyword=retrieval-augmented generation en-keyword=vector database kn-keyword=vector database en-keyword=schema-based extraction kn-keyword=schema-based extraction en-keyword=data sheet kn-keyword=data sheet en-keyword=technical information kn-keyword=technical information END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=110 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 Slide Annotation System with Multimodal Analysis for Video Presentation Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=With the rapid growth of online presentations, there has been an increasing need for efficient review of recorded materials. In typical presentations, speakers verbally elaborate on each slide, providing details not captured in the slides themselves. Automatically extracting and embedding these verbal explanations at their corresponding slide locations can greatly enhance the review process for audiences. This paper presents a Slide Annotation System that employs a robust hybrid two-stage detector to identify slide boundaries, extracts slide text through Optical Character Recognition (OCR), transcribes narration, and employs a multimodal Large Language Model (LLM) to generate concise, context-aware annotations that are added to their corresponding slide locations. For evaluations, the technical performance was validated on five recorded presentations, while the user experience was assessed by 37 participants. The results showed that the system achieved a macro-average ?1 score of 0.879 (??=0.024, 95% ??[0.849,0.909]) for slide segmentation and 90.0% accuracy (95% ??[74.4%,96.5%]) for annotation alignment. Subjective evaluations revealed high annotation validity and usefulness as rated by presenters, and a high System Usability Scale (SUS) score of 80.5 (??=6.7, 95% ??[78.3,82.7]). Qualitative feedback further confirmed that the system effectively streamlined the review process, enabling users to locate key information more efficiently than standard video playback. These findings demonstrate the strong potential of the proposed system as an effective automated annotation system. en-copyright= kn-copyright= en-aut-name=HazAmma Liesvarastranta en-aut-sei=Haz en-aut-mei=Amma Liesvarastranta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BrataKomang Candra en-aut-sei=Brata en-aut-mei=Komang Candra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KyawHtoo Htoo Sandi en-aut-sei=Kyaw en-aut-mei=Htoo Htoo Sandi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FajriantiEvianita Dewi en-aut-sei=Fajrianti en-aut-mei=Evianita Dewi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SukaridhotoSritrusta en-aut-sei=Sukaridhoto en-aut-mei=Sritrusta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=5 en-affil=Human Centric Multimedia Research Laboratory, Department of Informatic and Computer Engineering, Politeknik Elektronika Negeri Surabaya kn-affil= affil-num=6 en-affil=Human Centric Multimedia Research Laboratory, Department of Informatic and Computer Engineering, Politeknik Elektronika Negeri Surabaya kn-affil= en-keyword=slide annotation kn-keyword=slide annotation en-keyword=multimodal analysis kn-keyword=multimodal analysis en-keyword=speech-to-text kn-keyword=speech-to-text en-keyword=LLM kn-keyword=LLM en-keyword=SUS kn-keyword=SUS END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=1 article-no= start-page=65 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260109 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An SQL Query Description Problem with AI Assistance for an SQL Programming Learning Assistant System en-subtitle= kn-subtitle= en-abstract= kn-abstract=Today, relational databases are widely used in information systems. SQL (structured query language) is taught extensively in universities and professional schools across the globe as a programming language for its data management and accesses. Previously, we have studied a web-based programming learning assistant system (PLAS) to help novice students learn popular programming languages by themselves through solving various types of exercises. For SQL programming, we have implemented the grammar-concept understanding problem (GUP) and the comment insertion problem (CIP) for its initial studies. In this paper, we propose an SQL Query Description Problem (SDP) as a new exercise type for describing the SQL query to a specified request in a MySQL database system. To reduce teachersf preparation workloads, we integrate a generative AI-assisted SQL query generator to automatically generate a new SDP instance with a given dataset. An SDP instance consists of a table, a set of questions and corresponding queries. Answer correctness is determined by enhanced string matching against an answer module that includes multiple semantically equivalent canonical queries. For evaluation, we generated 11 SDP instances on basic topics using the generator, where we found that Gemini 3.0 Pro exhibited higher pedagogical consistency compared to ChatGPT-5.0, achieving perfect scores in Sensibleness, Topicality, and Readiness metrics. Then, we assigned the generated instances to 32 undergraduate students at the Indonesian Institute of Business and Technology (INSTIKI). The results showed an average correct answer rate of 95.2% and a mean SUS score of 78, which demonstrates strong initial student performance and system acceptance. en-copyright= kn-copyright= en-aut-name=WardaniNi Wayan en-aut-sei=Wardani en-aut-mei=Ni Wayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KyawHtoo Htoo Sandi en-aut-sei=Kyaw en-aut-mei=Htoo Htoo Sandi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhuZihao en-aut-sei=Zhu en-aut-mei=Zihao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KotamaI Nyoman Darma en-aut-sei=Kotama en-aut-mei=I Nyoman Darma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiartawanPutu en-aut-sei=Sugiartawan en-aut-mei=Putu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PutraI Nyoman Agus Suarya en-aut-sei=Putra en-aut-mei=I Nyoman Agus Suarya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Business and Creative Design, Indonesian Institute of Business and Technology kn-affil= en-keyword=database programming kn-keyword=database programming en-keyword=SQL query description problem (SDP) kn-keyword=SQL query description problem (SDP) en-keyword=self-study kn-keyword=self-study en-keyword=programming learning assistant system (PLAS) kn-keyword=programming learning assistant system (PLAS) en-keyword=generative AI kn-keyword=generative AI END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=2 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251226 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Threshold Selection Method in Code Plagiarism Checking Function for Code Writing Problem in Java Programming Learning Assistant System Considering AI-Generated Codes en-subtitle= kn-subtitle= en-abstract= kn-abstract=To support novice learners, the Java programming learning assistant system (JPLAS) has been developed with various features. Among them, code writing problem (CWP) assigns writing an answer code that passes a given test code. The correctness of an answer code is validated by running it on JUnit. In previous works, we implemented a code plagiarism checking function that calculates the similarity score for each pair of answer codes based on the Levenshtein distance. When the score is higher than a given threshold, this pair is regarded as plagiarism. However, a method for finding the proper threshold has not been studied. In addition, AI-generated codes have become threats in plagiarism, as AI has grown in popularity, which should be investigated. In this paper, we propose a threshold selection method based on Tukeyfs IQR fences. It uses a custom upper threshold derived from the statistical distribution of similarity scores for each assignment. To better accommodate skewed similarity distributions, the method introduces a simple percentile-based adjustment for determining the upper threshold. We also design prompts to generate answer codes using generative AI and apply them to four AI models. For evaluation, we used a total of 745 source codes of two datasets. The first dataset consists of 420 answer codes across 12 CWP instances from 35 first-year undergraduate students in the State Polytechnic of Malang, Indonesia (POLINEMA). The second dataset includes 325 answer codes across five CWP assignments from 65 third-year undergraduate students at Okayama University, Japan. The applications of our proposals found the following: (1) any pair of student codes whose score is higher than the selected threshold has some evidence of plagiarism, (2) some student codes have a higher similarity than the threshold with AI-generated codes, indicating the use of generative AI, and (3) multiple AI models can generate code that resembles student-written code, despite adopting different implementations. The validity of our proposal is confirmed. en-copyright= kn-copyright= en-aut-name=PermatasariPerwira Annissa Dyah en-aut-sei=Permatasari en-aut-mei=Perwira Annissa Dyah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MentariMustika en-aut-sei=Mentari en-aut-mei=Mustika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KinariSafira Adine en-aut-sei=Kinari en-aut-mei=Safira Adine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AungSoe Thandar en-aut-sei=Aung en-aut-mei=Soe Thandar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KyawHtoo Htoo Sandi en-aut-sei=Kyaw en-aut-mei=Htoo Htoo Sandi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WaiKhaing Hsu en-aut-sei=Wai en-aut-mei=Khaing Hsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Engineering Science, Akita University kn-affil= en-keyword=Java programming learning kn-keyword=Java programming learning en-keyword=JPLAS kn-keyword=JPLAS en-keyword=JUnit kn-keyword=JUnit en-keyword=code writing problem kn-keyword=code writing problem en-keyword=plagiarism kn-keyword=plagiarism en-keyword=Levenshtein distance kn-keyword=Levenshtein distance en-keyword=threshold kn-keyword=threshold en-keyword=IQR kn-keyword=IQR en-keyword=AI-generated kn-keyword=AI-generated END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=69 end-page=74 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=Effective Treatment of Advanced Hepatocellular Carcinoma with Extensive Peritoneal Dissemination Using Lenvatinib en-subtitle= kn-subtitle= en-abstract= kn-abstract=Patients with hepatocellular carcinoma (HCC) and extensive peritoneal dissemination generally have a poor prognosis and are often resistant to systemic therapy. We report the case of a 47-year-old woman with HCC and massive peritoneal dissemination who presented with malignant ascites requiring repeated cell-free and concentrated ascites reinfusion therapy and peritoneovenous shunt placement, as well as malignant pleural effusion requiring pleurodesis. Combined immunotherapy with durvalumab/tremelimumab was initiated;however, disease progression was observed after three treatment courses, prompting a switch to lenvatinib therapy. Two months after initiation of lenvatinib, CT imaging demonstrated complete disappearance of arterial enhancement in the primary hepatic lesion, along with reduction in the size of peritoneal dissemination nodules. Thirteen months after switching to lenvatinib (16 months after the initial diagnosis), the alpha-fetoprotein level continued to decrease, and the disease remained stable under treatment. Despite the extremely high tumor burden, lenvatinib achieved disease stabilization and symptomatic improvement. en-copyright= kn-copyright= en-aut-name=WakatsukiShinya en-aut-sei=Wakatsuki en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakamotoShinya en-aut-sei=Sakamoto en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UenoAkiko en-aut-sei=Ueno en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NambaTakaomi en-aut-sei=Namba en-aut-mei=Takaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoYorito en-aut-sei=Yamamoto en-aut-mei=Yorito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoManabu en-aut-sei=Matsumoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataJun en-aut-sei=Iwata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Kochi Health Sciences Center kn-affil= en-keyword=diagnostic laparoscopy kn-keyword=diagnostic laparoscopy en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=peritoneal dissemination kn-keyword=peritoneal dissemination en-keyword=lenvatinib kn-keyword=lenvatinib END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=63 end-page=67 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=Metastatic Intraocular Tumor Likely from Hepatocellular Carcinoma Mimicking Panuveitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 77-year-old man undergoing treatment for hepatocellular carcinoma (HCC) presented with blurred vision in his right eye, persisting for 2 months. Slit-lamp microscopy and fundus examination revealed inflammatory cells in the anterior chamber, severe vitreous opacities, and retinal vasculitis in the right eye. The patient underwent vitreous surgery with biopsy, and vitreous cytology confirmed a metastatic intraocular tumor originating from the HCC. Radiotherapy was administered to the right eye, with no recurrence of intraocular inflammation observed at 10 months post-irradiation. en-copyright= kn-copyright= en-aut-name=TakasuEri en-aut-sei=Takasu en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KindoHiroya en-aut-sei=Kindo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HosokawaMio en-aut-sei=Hosokawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AdachiTakuya en-aut-sei=Adachi en-aut-mei=Takuya 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= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of 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 Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=metastatic intraocular tumor kn-keyword=metastatic intraocular tumor en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=panuveitis kn-keyword=panuveitis en-keyword=uveitis masquerade syndrome kn-keyword=uveitis masquerade syndrome END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=55 end-page=62 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=Changes in Prescribing Patterns of Antiviral Drugs before and after Public Coverage Termination among Hospitalized COVID-19 Patients in Regional Hospitals in Japan: A Retrospective, Multicenter Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=In Japan, antiviral agents for COVID-19 were freely available until September 2023 as part of national policy. This study evaluated changes in these agentsf prescribing patterns and the patient outcomes following the policy shift. We conducted a multicenter retrospective study at four hospitals in Japanfs Okayama and Kagawa prefectures from January 2022 to March 2024. The study period was divided into the public-expenditure phase (January 2022 to September 2023) and the post-expenditure phase (October 2023 to March 2024). We extracted the hospitalized patientsf clinical data from the electronic database. The studyfs primary outcome was the antiviral prescription rate; the secondary outcome was in-hospital mortality. Among the 302 hospitalized patients (median age 85 years), 52.0% were classified as having a mild condition. Of the patients with mild conditions, 37.7% were diagnosed in outpatient settings prior to hospitalization. During the public-expenditure phase, 47.4% of the patients received antivirals as outpatients, mainly molnupiravir (80.9%). In the post-expenditure period, 80.0% of the patients were prescribed antivirals, mostly molnupiravir (91.7%). The antiviral prescription rate was significantly higher after the policy change. The overall in-hospital mortality was 15.8%, with no significant difference between the two periods (17.0% vs. 10.5%). Despite the termination of government funding, antiviral prescriptions remained frequent at community hospitals located in highly aging regions of western Japan such as Okayama and Kagawa prefectures. Mortality remains high among the elderly, highlighting the need for continued antiviral therapy and booster vaccinations. en-copyright= kn-copyright= en-aut-name=AkazawaHidemasa en-aut-sei=Akazawa en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoShohei en-aut-sei=Yamamoto en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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 Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of 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= en-keyword=coronavirus disease 2019 kn-keyword=coronavirus disease 2019 en-keyword=public expenditure kn-keyword=public expenditure en-keyword=prescribing pattern kn-keyword=prescribing pattern en-keyword=prognosis kn-keyword=prognosis en-keyword=Japan kn-keyword=Japan END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=31 end-page=37 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Preoperative Anterior Pelvic Plane Angle Predicts Cup Anteversion Changes at 1 Year after Total Hip Arthroplasty en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated global alignment changes following total hip arthroplasty (THA) and predictive alignment parameters for increased cup anteversion (CA) by retrospectively analyzing the primary THA data of 75 patients treated at our hospital (49 women, 26 men; age 65.1}5.7 years, BMI 28.3}3.4 kg/m2). Global alignment parameters, i.e., the anterior pelvic plane angle (APPa) and proximal femoral shaft angle (PFSa) and other alignment parameters were measured. CA was evaluated based on the patientsf standing coronal radiographs. ƒ¢CA was defined as the difference in CA from 2 weeks before to 1 year after each THA. We classified the cases as stable (S) (CA < 10‹; n=63) and pelvic retroversion (R) (CA ? 10‹; n=12) groups. Associations between ƒ¢CA and alignment parameters were evaluated by linear regression and a receiver operating characteristic (ROC) analysis. A significant decrease in the PFSa occurred between the 2-week and 1-year post-THA timepoints (7.8}4.3‹ vs. 4.2}3.6‹, p<0.001), with no notable change in other alignment parameters. At 1-year post-THA, the CA of 12 (16%) patients had increased to 4.5}4.4‹. Only the preoperative APPa was positively associated with ƒ¢CA (ƒÀ=0.165, p=0.020). The ROC analysis revealed that the optimal cut-off value for increased CA in the APPa is 2.1‹ (area under the curve, 0.700; p=0.020; odds ratio, 4.80). The APPa change predicted increased CA, which emphasizes the importance of the use of preoperative standing radiography for identifying the optimal cup positioning for post-THA changes in CA. en-copyright= kn-copyright= en-aut-name=IshibashiKyota en-aut-sei=Ishibashi en-aut-mei=Kyota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OishiHirotaka en-aut-sei=Oishi en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ArakiRyo en-aut-sei=Araki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawamuraKosuke en-aut-sei=Kawamura en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasakiIsamu en-aut-sei=Sasaki en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SasakiEiji en-aut-sei=Sasaki en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamadaHikaru en-aut-sei=Kamada en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KogawaMasakazu en-aut-sei=Kogawa en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanakaSunao en-aut-sei=Tanaka en-aut-mei=Sunao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NumasawaTakuya en-aut-sei=Numasawa en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshibashiYasuyuki en-aut-sei=Ishibashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Hachinohe City Hospital kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine kn-affil= en-keyword=total hip arthroplasty kn-keyword=total hip arthroplasty en-keyword=global alignment kn-keyword=global alignment en-keyword=anterior pelvic plane kn-keyword=anterior pelvic plane en-keyword=cup anteversion kn-keyword=cup anteversion en-keyword=pelvic tilt kn-keyword=pelvic tilt END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=17 end-page=30 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=Development of a Stroke Discharge Support Evaluation Scale for Ward Nurses in Acute Care Hospitals en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to develop a scale enabling nurses to objectively evaluate their own stroke discharge support, as a basis for enhancing its overall effectiveness. A draft scale was created based on a literature review, and consisted of a 51-item, 5-point Likert-type questionnaire administered to ward nurses engaged in stroke discharge support at acute care hospitals. Factor analysis was performed to refine the scale. Construct validity was assessed using the known-groups method, and reliability was evaluated through internal consistency analysis. The resulting Stroke Discharge Support Evaluation Scale comprises 29 items across 5 factors, each rated on a 5-point Likert scale. Analysis of the data collected from 237 valid responses demonstrated good internal consistency and supported the scalefs construct validity. The Stroke Discharge Support Evaluation Scale is a reliable and valid tool enabling ward nurses in acute care hospitals to evaluate their own stroke discharge support. en-copyright= kn-copyright= en-aut-name=YanoHideki en-aut-sei=Yano en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahataYoko en-aut-sei=Takahata en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamaguchiTakeshi en-aut-sei=Yamaguchi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoShinya en-aut-sei=Saito en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Nursing, Faculty of Human Health Sciences, Niimi University kn-affil= affil-num=2 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Nursing, Shikoku University kn-affil= affil-num=4 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=stroke kn-keyword=stroke en-keyword=discharge support kn-keyword=discharge support en-keyword=scale development kn-keyword=scale development END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1 article-no= start-page=9 end-page=16 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=A Novel Nomogram that Predicts Chronic Hemodialysis Patientsf Survival Based on Their Sedentary Behavior en-subtitle= kn-subtitle= en-abstract= kn-abstract=Appropriate treatments for chronic hemodialysis patients are a public health challenge in Japan. Sedentary behavior appears to be closely associated with these patientsf survival. We thus sought to develop a nomogram that predicts survival based on the duration of chronic hemodialysis patientsf sedentary behavior. One hundred twenty-four patients under chronic hemodialysis (73 men, 51 women, age 71.7}11.1 years) were enrolled in this cohort study. The patients wore a triaxial accelerometer that measured both their sedentary behavior, i.e., total sedentary behavior (minutes) and their maximum sedentary bouts (min) on non-hemodialysis days. We obtained the Kaplan-Meier curve and used the log-rank test and a Cox proportional hazards model to evaluate the relationship between the patientsf sedentary behavior and their survival. We also used a Cox proportional hazards model to develop a nomogram for the patientsf 5-year survival rate. Forty-six patients died during the follow-up period. When we stratified the patients by the medians of total sedentary behavior and maximum sedentary bouts, we observed significant between-group differences. After adjustment for confounding factors in a Cox proportional hazards model, total sedentary behavior and maximum sedentary bouts were identified as critical survival factors, and we generated a nomogram using an index of sedentary behavior. Our analysis results demonstrated that sedentary behavior on non-dialysis days was closely associated with the survival of the chronic hemodialysis patients, suggesting that a decrease in sedentary behavior would prolong their survival. The nomogram developed herein based on sedentary behavior may be useful for predicting the outcomes of chronic hemodialysis patients. en-copyright= kn-copyright= en-aut-name=SugaharaKentaro en-aut-sei=Sugahara en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoTakashi en-aut-sei=Kondo en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyatakeNobuyuki en-aut-sei=Miyatake en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiHiroyuki en-aut-sei=Nishi en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UjikeKazuhiro en-aut-sei=Ujike en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoumotoKiichi en-aut-sei=Koumoto en-aut-mei=Kiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NamioKeiichi en-aut-sei=Namio en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HishiiShuhei en-aut-sei=Hishii en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KatayamaAkihiko en-aut-sei=Katayama en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SuzukiHiromi en-aut-sei=Suzuki en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoYorimasa en-aut-sei=Yamamoto en-aut-mei=Yorimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=2 en-affil=Innoshima General Hospital kn-affil= affil-num=3 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=4 en-affil=Innoshima General Hospital kn-affil= affil-num=5 en-affil=Innoshima General Hospital kn-affil= affil-num=6 en-affil=Innoshima General Hospital kn-affil= affil-num=7 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=8 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Faculty of Social Studies, Shikokugakuin University kn-affil= affil-num=10 en-affil=Department of Hygiene, Faculty of Medicine, Kagawa University kn-affil= affil-num=11 en-affil=Innoshima General Hospital kn-affil= en-keyword=nomogram kn-keyword=nomogram en-keyword=chronic hemodialysis kn-keyword=chronic hemodialysis en-keyword=sedentary behavior kn-keyword=sedentary behavior en-keyword=Cox proportional hazards model kn-keyword=Cox proportional hazards model en-keyword=Kaplan- Meier curve kn-keyword=Kaplan- Meier curve END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue= article-no= start-page=54 end-page=73 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The trajectory of rural field research and modernization discourse in American area studies: The Intersection of the University of Michiganfs Center for Japanese Studies Okayama Field Station, J. W. Hall, and the Seto Inland Sea Cultural Research Group kn-title=Area Studies ‚Ì‚È‚©‚Ìu’nˆæŽjvŒ¤‹† [—ðŽjŒ¤‹†ŽÒAJEWEƒz[ƒ‹‚©‚猩‚éƒ~ƒVƒKƒ“‘剪ŽR•ªŽº‚Æ£ŒË“àŠC‘‡Œ¤‹†‰ï[ en-subtitle= kn-subtitle= en-abstract= kn-abstract=During the late Allied occupation and the 1950s, the University of Michiganfs Center for Japanese Studies established a field station in Okayama, where American scholars conducted rural research. This article examines the challenges of academic research under occupation and analyzes how such research was organized through specific actors and institutional arrangements, with particular attention to its intersection with the academic knowledge of the host institution, Okayama University. Focusing on the historian John W. Hall, it traces the activities of the Michigan field station and explores its interactions with Okayama University and the Seto Inland Sea Cultural Research Group. The article argues that while archival research?understood as a form of fieldwork?facilitated collaborative research, differing conceptions of rural society constituted a critical point of divergence in the production of scholarly knowledge. en-copyright= kn-copyright= en-aut-name=OSAShizue en-aut-sei=OSA en-aut-mei=Shizue kn-aut-name=’·ŽuŽìŠG kn-aut-sei=’· kn-aut-mei=ŽuŽìŠG aut-affil-num=1 ORCID= affil-num=1 en-affil=Kobe University kn-affil= en-keyword=Michigan CJS Okayama Field Station kn-keyword=Michigan CJS Okayama Field Station en-keyword=John W. Hall kn-keyword=John W. Hall en-keyword=the Seto Inland Sea Cultural Research Group kn-keyword=the Seto Inland Sea Cultural Research Group en-keyword=Sumio Taniguchi kn-keyword=Sumio Taniguchi en-keyword=Rural Field Research kn-keyword=Rural Field Research en-keyword=Modernization Discourse kn-keyword=Modernization Discourse END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue= article-no= start-page=20 end-page=39 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Radiocarbon dating, dietary habits, and genetic characteristics of ancient skeletal remains excavated from the Inome Cave Site in Shimane Prefecture kn-title=“‡ªŒ§’––Ú“´ŒAˆâÕo“ylœ‚Ì”N‘ãEH«Eˆâ“`“I“Á’¥ en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper reports on the integrative research findings of the human bones excavated from the Inome Cave Site in Shimane Prefecture, based on dietary estimation using carbon and nitrogen isotope analysis, radiocarbon dating, and whole genome analysis. The dates of the analyzed human bones span a wide range, from the Middle to Late Kofun period, the Nara period to the Early Heian period, and the Middle to Late Heian period, indicating that the Inome Cave Site was continuously used as a burial place. Dietary habits were a mixture of C3 resources (C3 plants and terrestrial animals that consumed C3 plants) and marine resources, with individual variations in the intake of marine and terrestrial resources. A correlation was observed between differences in dietary habits and individual variations in the Jomon ratio in the nuclear genome, with individuals who consumed higher amounts of marine resources tending to have a higher Jomon ratio. This suggests that individuals with different backgrounds were buried in the same site due to interactions with surrounding settlements. en-copyright= kn-copyright= en-aut-name=KANZAWA-KIRIYAMAHideaki en-aut-sei=KANZAWA-KIRIYAMA en-aut-mei=Hideaki kn-aut-name=_àVG–¾ kn-aut-sei=_àV kn-aut-mei=G–¾ aut-affil-num=1 ORCID= en-aut-name=TAKIGAMIMai en-aut-sei=TAKIGAMI en-aut-mei=Mai kn-aut-name=‘ëã•‘ kn-aut-sei=‘ëã kn-aut-mei=•‘ aut-affil-num=2 ORCID= en-aut-name=KAKUDATsuneo en-aut-sei=KAKUDA en-aut-mei=Tsuneo kn-aut-name=Šp“cP—Y kn-aut-sei=Šp“c kn-aut-mei=P—Y aut-affil-num=3 ORCID= en-aut-name=SPEIDELLeo en-aut-sei=SPEIDEL en-aut-mei=Leo kn-aut-name=ƒVƒ…ƒpƒCƒfƒ‹ƒŒƒI kn-aut-sei=ƒVƒ…ƒpƒCƒfƒ‹ kn-aut-mei=ƒŒƒI aut-affil-num=4 ORCID= en-aut-name=HELLENTHALGarrett en-aut-sei=HELLENTHAL en-aut-mei=Garrett kn-aut-name=ƒwƒŒƒ“ƒ^[ƒ‹ƒKƒŒƒbƒg kn-aut-sei=ƒwƒŒƒ“ƒ^[ƒ‹ kn-aut-mei=ƒKƒŒƒbƒg aut-affil-num=5 ORCID= en-aut-name=BIRDNancy en-aut-sei=BIRD en-aut-mei=Nancy kn-aut-name=ƒo[ƒhƒiƒ“ƒV[ kn-aut-sei=ƒo[ƒh kn-aut-mei=ƒiƒ“ƒV[ aut-affil-num=6 ORCID= en-aut-name=KAWAIYousuke en-aut-sei=KAWAI en-aut-mei=Yousuke kn-aut-name=‰Í‡—m‰î kn-aut-sei=‰Í‡ kn-aut-mei=—m‰î aut-affil-num=7 ORCID= en-aut-name=NCBN Controls WGS Consortium en-aut-sei=NCBN Controls WGS Consortium en-aut-mei= kn-aut-name=NCBN ƒRƒ“ƒgƒ[ƒ‹ WGS ƒRƒ“ƒ\[ƒVƒAƒ€ kn-aut-sei=NCBN ƒRƒ“ƒgƒ[ƒ‹ WGS ƒRƒ“ƒ\[ƒVƒAƒ€ kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SAKAMOTOMinoru en-aut-sei=SAKAMOTO en-aut-mei=Minoru kn-aut-name=â–{–« kn-aut-sei=â–{ kn-aut-mei=–« aut-affil-num=9 ORCID= en-aut-name=KAMEDAYuichi en-aut-sei=KAMEDA en-aut-mei=Yuichi kn-aut-name=‹T“c—Eˆê kn-aut-sei=‹T“c kn-aut-mei=—Eˆê aut-affil-num=10 ORCID= en-aut-name=ADACHINoboru en-aut-sei=ADACHI en-aut-mei=Noboru kn-aut-name=ˆÀ’B“o kn-aut-sei=ˆÀ’B kn-aut-mei=“o aut-affil-num=11 ORCID= en-aut-name=SHINODAKen-ichi en-aut-sei=SHINODA en-aut-mei=Ken-ichi kn-aut-name=ŽÂ“cŒªˆê kn-aut-sei=ŽÂ“c kn-aut-mei=Œªˆê aut-affil-num=12 ORCID= en-aut-name=SAITOUNaruya en-aut-sei=SAITOU en-aut-mei=Naruya kn-aut-name=Ö“¡¬–ç kn-aut-sei=Ö“¡ kn-aut-mei=¬–ç aut-affil-num=13 ORCID= en-aut-name=HAMADATatsuhiko en-aut-sei=HAMADA en-aut-mei=Tatsuhiko kn-aut-name=ûM“c—³•F kn-aut-sei=ûM“c kn-aut-mei=—³•F aut-affil-num=14 ORCID= affil-num=1 en-affil=Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture kn-affil= affil-num=2 en-affil=Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture kn-affil= affil-num=3 en-affil=Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi kn-affil= affil-num=4 en-affil=Center for Interdisciplinary Theoretical and Mathematical Sciences, RIKEN kn-affil= affil-num=5 en-affil=Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London kn-affil= affil-num=6 en-affil=Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London kn-affil= affil-num=7 en-affil=Genome Medical Science Project, National Institute of Global Health and Medicine, National Institute for Health Security kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil=National Museum of Japanese History kn-affil= affil-num=10 en-affil=Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture kn-affil= affil-num=11 en-affil=Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi kn-affil= affil-num=12 en-affil=National Museum of Nature and Science kn-affil= affil-num=13 en-affil=National Institute of Genetics kn-affil= affil-num=14 en-affil=Research Institute for the Dynamics of Civilizations, Okayama University kn-affil= en-keyword=Inome Cave Site kn-keyword=Inome Cave Site en-keyword=human bone kn-keyword=human bone en-keyword=radiocarbon dating kn-keyword=radiocarbon dating en-keyword=dietary habits kn-keyword=dietary habits en-keyword=ancient genome kn-keyword=ancient genome END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue= article-no= start-page=1 end-page=19 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The gRussian Fluh pandemic in Japan, 1889-1891: A social-historical perspective kn-title=“ú–{‚É‚¨‚¯‚éuƒƒVƒA‚©‚ºv—¬s‚̎ЉïŽj“I•ªÍ \1889 -1891 ”Nƒpƒ“ƒfƒ~ƒbƒN‚Æ“ú–{ŽÐ‰ï\ en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study offers a social-historical analysis of the gRussian fluh pandemic in Japan (1889?1891). Due to scarce statistical data, the study relies primarily on contemporary newspapers and magazines. It identifies two distinct epidemic waves: the first in spring-summer 1890, and the second from late 1890 to spring 1891. The first wave, though widespread, was overshadowed by a concurrent cholera epidemic and caused relatively few deaths, whereas the second wave was far more lethal and generated widespread fear. At the time, influenza remained an gunknown diseaseh, with unclear etiology and no established treatments. People responded with diverse measures, from purchasing patent medicines and using folk remedies to symbolic practices such as "disease naming" (osome-kaze). The crisis also renewed attention to historical records of earlier influenza-like epidemics in Japan. In contrast, by the time of the later gSpanish fluh pandemic, advances in bacteriology had already rendered influenza a medically defined disease. This comparison highlights how shifting medical knowledge shaped societal responses. The findings not only corroborate previous excess-mortality analyses but also provide new historical insights into how societies have historically confronted pandemics. en-copyright= kn-copyright= en-aut-name=KAWAUCHIAtsushi en-aut-sei=KAWAUCHI en-aut-mei=Atsushi kn-aut-name=ì“à~Žj kn-aut-sei=ì“à kn-aut-mei=~Žj aut-affil-num=1 ORCID= affil-num=1 en-affil=Uehiro Disaster Risk Reduction Research Division, International Research Institute of Disaster Science (IRIDeS), TOHOKU UNIVERSITY kn-affil= en-keyword=Russian flu kn-keyword=Russian flu en-keyword=influenza pandemic kn-keyword=influenza pandemic en-keyword=epidemic waves kn-keyword=epidemic waves en-keyword=social history kn-keyword=social history en-keyword=unknown disease kn-keyword=unknown disease en-keyword=modern Japan kn-keyword=modern Japan 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? 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=33 cd-vols= no-issue=4 article-no= start-page=201045 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Collagen depletion by pirfenidone enhances antitumor effect of oncolytic adenovirus against peritoneal metastases of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) play a crucial role in collagen accumulation, which develops and promotes peritoneal metastasis (PM) in gastric cancer (GC). In addition, the abundant stromal collagens in the tumor microenvironment function as a physical barrier against penetration of antitumor drugs and oncolytic viruses. This study investigated whether collagen depletion by pirfenidone (PFD), an antifibrotic drug, enhances the antitumor effects of oncolytic adenoviruses. Analysis of the clinical samples revealed a significant association of high expression of collagen 1 and ƒ¿-smooth muscle actin (ƒ¿-SMA) with PM development and poor prognosis of advanced GC. Human and murine GC cells enhanced collagen production by fibroblasts, which was suppressed by PFD. Abundant fibroblasts and collagen inhibited the penetration of OBP-702, which reduced the antitumor effects of OBP-702 in the spheroid model. Intraperitoneal co-injection of GC cells and fibroblasts promoted the development of collagen-rich PM and reduced the antitumor effects of OBP-702 in vivo model. PFD suppressed collagen production in PM and improved viral penetration into the tumors, which enhanced the antitumor effects of OBP-702 against PM of GC. Collagen depletion by PFD enhances the penetration of OBP-702 into PM of GC, in turn enhancing the antitumor effects of OBP-702 against PM of GC. en-copyright= kn-copyright= en-aut-name=OkuraTomohiro en-aut-sei=Okura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=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=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuiEma en-aut-sei=Mitsui en-aut-mei=Ema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UneYuta en-aut-sei=Une en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhtsukaJunko en-aut-sei=Ohtsuka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhkiRieko en-aut-sei=Ohki en-aut-mei=Rieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=13 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute 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= Oncolys BioPharma, Inc. kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=MT: Regular Issue kn-keyword=MT: Regular Issue en-keyword=oncolytic virotherapy kn-keyword=oncolytic virotherapy en-keyword=peritoneal metastasis kn-keyword=peritoneal metastasis en-keyword=gastric cancer kn-keyword=gastric cancer en-keyword=collagen kn-keyword=collagen en-keyword=pirfenidone kn-keyword=pirfenidone END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=9 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Influence of Fluidic Flow Stress on the Development of the Secondary Palate en-subtitle= kn-subtitle= en-abstract= kn-abstract=Craniofacial development is orchestrated by a finely regulated interplay of numerous genes and signaling pathways. Palatogenesis proceeds through a complex, stepwise process, in which endogenous mechanical stresses within tissues have been implicated. However, the impact of exogenous fluidic flow mechanical stress derived from maternal movement on palatal development remains unclear. In this study, we investigated the effect of exogenous fluidic flow mechanical stress on palatal morphogenesis, focusing on the horizontal outgrowth of palatal shelves after elevation. Palatal tissues dissected from mouse embryos were subjected to organ culture with or without mechanical loading (loaded and unloaded groups, respectively). Stress magnitude was quantified by calculating wave energy, and morphometric and molecular analyses were performed. Compared with the unloaded group, palatal shelves in the loaded group showed significant increases in thickness and volume, accompanied by enhanced cell proliferation, nuclear translocation of YAP and ƒÀ-catenin, and upregulation of the osteogenic markers Osterix and Osteocalcin. No significant difference in apoptosis was observed. These findings indicate that exogenous mechanical stress promotes cell proliferation and osteogenic differentiation through the Hippo and WNT/ƒÀ-catenin pathways in palate explants. Our results suggest that moderate maternal movement-induced mechanical stress contributes to normal palatogenesis, providing new insights into the mechanisms underlying cleft palate. en-copyright= kn-copyright= en-aut-name=NagataMasayo en-aut-sei=Nagata en-aut-mei=Masayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayanoSatoru en-aut-sei=Hayano en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KosamiTakahiro en-aut-sei=Kosami en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamiokaHiroshi en-aut-sei=Kamioka 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 Orthodontics, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Orthodontics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=mechanical stress kn-keyword=mechanical stress en-keyword=palatal development kn-keyword=palatal development en-keyword=ƒÀ-catenin kn-keyword=ƒÀ-catenin en-keyword=YAP kn-keyword=YAP END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=1 article-no= start-page=100731 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=Insights into the taste of organic acids via TAS1Rs en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Organic acids contribute significantly to the flavor of fermented foods by imparting sourness. Although mice generally avoid sour taste, previous studies have reported greater consumption of l-lactic acid than its d-enantiomer, suggesting enantiomer-specific recognition. This behavior is hypothesized to involve TAS1Rs, which consists of sweet/umami receptors. However, it remains unclear whether TAS1Rs additionally contribute to the recognition of other chiral organic acids. This study aimed to evaluate the role of TAS1Rs, particularly TAS1R3, in the modulation of enantiomer-dependent behavioral responses to organic acids in mice.
Methods: Behavioral responses were evaluated using 48-h and 1-h 2-bottle tests. Binding of organic acids to TAS1Rs was investigated by differential scanning fluorimetry (DSF) with the ligand-binding domain (LBD) of medaka Tas1r2a/Tas1r3.
Results: Wild-type mice consumed more d-malic acid than l-malic acid in the 48-h test, whereas Tas1r3-KO mice showed no such difference. This pattern was not observed in the short-term 1-h test, which minimized the contribution of post-ingestion and learned effects. DSF analysis revealed no binding of any of the tested organic acids to the LBD of medaka Tas1r2a/Tas1r3.
Conclusions: Organic acids may elicit TAS1R3-dependent post-ingestion signals that contribute to enantiomer-selective consumption in mice. Electrostatic interactions and hydrogen-bonding networks within the orthosteric pocket of TAS1Rs may account for the differences in binding affinity to the LBD of medaka Tas1r2a/Tas1r3 between organic acids and L-alanine, a known ligand. en-copyright= kn-copyright= en-aut-name=YamaseYuko en-aut-sei=Yamase en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakebeKatsuki en-aut-sei=Takebe en-aut-mei=Katsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HorieKengo en-aut-sei=Horie en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamashitaAtsuko en-aut-sei=Yamashita en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Institute for Protein Research, The University of Osaka kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Taste detection kn-keyword=Taste detection en-keyword=Organic acid preference kn-keyword=Organic acid preference en-keyword=G-protein coupled receptor (GPCR) kn-keyword=G-protein coupled receptor (GPCR) en-keyword=Knockout mice kn-keyword=Knockout mice en-keyword=Surface electrostatic potential kn-keyword=Surface electrostatic potential END start-ver=1.4 cd-journal=joma no-vol=178 cd-vols= no-issue=1 article-no= start-page=e70775 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reactive Carbonyl Species Mediate Isothiocyanate Signaling Pathway in Arabidopsis thaliana Guard Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Our previous results demonstrated that depletion of glutathione (GSH) rather than elevation of levels of reactive oxygen species (ROS) is highly correlated with the decrease in stomatal aperture induced by isothiocyanates (ITCs), although ROS is considered a key second messenger in stomatal closure, suggesting that another signal component regulates stomatal apertures along with GSH depletion. This study, using Arabidopsis, clarified that reactive carbonyl species (RCS), especially acrolein and 4-hydroxy-(E)-2-nonenal, are determinants of stomatal aperture responses to ITCs. All tested ITCs, allyl isothiocyanate (AITC), sulforaphane (SFN), benzyl isothiocyanate (BITC), and phenethyl isothiocyanate (PEITC), significantly induced stomatal closure, which was inhibited by the RCS scavengers, carnosine and pyridoxamine. The RCS scavengers suppressed ITC-induced depletion of GSH but not elevation of ROS levels. All tested ITCs (AITC, SFN, BITC, and PEITC) increased levels of RCS and non-RCS aldehydes in the epidermal tissues. However, acrolein, 4-hydroxy-(E)-2-nonenal, crotonaldehyde, and (E)-2-pentenal induced stomatal closure at 10 and 100?ƒÊM, whereas propionaldehyde, butyraldehyde, and n-pentanal did not at concentrations up to 100?ƒÊM. Acrolein and 4-hydroxy-(E)-2-nonenal more effectively induced stomatal closure and GSH depletion than crotonaldehyde and (E)-2-pentenal did. The contents of RCS were more strongly correlated with GSH levels and stomatal closure than with ROS levels. These results suggest that RCS, especially acrolein and 4-hydroxy-(E)-2-nonenal, acts as key regulators of stomatal closure in guard cells in response to ITCs. en-copyright= kn-copyright= en-aut-name=FarzanaSumaiya en-aut-sei=Farzana en-aut-mei=Sumaiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IslamMd. Moshiul en-aut-sei=Islam en-aut-mei=Md. Moshiul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraToshiyuki en-aut-sei=Nakamura en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MunemasaShintaro en-aut-sei=Munemasa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ManoJun'ichi en-aut-sei=Mano en-aut-mei=Jun'ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= 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 Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Science Research Center, Yamaguchi University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=arabidopsis kn-keyword=arabidopsis en-keyword=GSH depletion kn-keyword=GSH depletion en-keyword=isothiocyanate kn-keyword=isothiocyanate en-keyword=reactive carbonyl species kn-keyword=reactive carbonyl species en-keyword=reactive oxygen species kn-keyword=reactive oxygen species END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=9 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sodium butyrate augments the antibacterial activity of tetracycline against clinical isolates of multidrug-resistant Vibrio cholerae en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Antibiotic resistance poses a major challenge in treating Vibrio cholerae infections. One promising method to counter resistance is the co-administration of antibiotics with non-antibiotic adjuvants to enhance their efficacy. This study investigated the combined action of sodium butyrate (SB) and tetracycline on tetracycline-resistant V. cholerae strains.
Results The combined activity of SB and antibiotics was assessed on eight V. cholerae clinical isolates using the Fractional Inhibitory Concentration Index (FICI), with SB-Tetracycline showing strong synergy (FICI: 0.09?0.5). Functional and mechanistic studies, including time-kill kinetics, live/dead staining, SEM-based morphological analysis, and fluorometric assays, demonstrated a synergistic antibacterial effect of SB and Tetracycline. This effect was associated with increased membrane permeability, disruption of membrane integrity, dissipation of the proton motive force, and suppression of efflux activity. These changes collectively led to membrane damage, enhanced intracellular accumulation of Tetracycline, decreased intracellular ATP levels, and ultimately, bacterial cell death. Moreover, GM1-CT ELISA and fluorescence microscopy revealed the synergistic anti-virulence activity of the SB- Tetracycline combination. Finally, the combination of SB and Tetracycline showed enhanced efficacy in animal models compared with monotherapy.
Conclusion: The observed SB-Tetracycline synergy provides a promising therapeutic approach to overcome tetracycline resistance in V. cholerae, offering a potential adjunct strategy for the management of antibiotic-resistant cholera infections. en-copyright= kn-copyright= en-aut-name=KunduSushmita en-aut-sei=Kundu en-aut-mei=Sushmita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AluSourin en-aut-sei=Alu en-aut-mei=Sourin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SinghAbhishek en-aut-sei=Singh en-aut-mei=Abhishek kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GopeAnimesh en-aut-sei=Gope en-aut-mei=Animesh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NandyRanjan Kumar en-aut-sei=Nandy en-aut-mei=Ranjan Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MukhopadhyayAsish K. en-aut-sei=Mukhopadhyay en-aut-mei=Asish K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChatterjeeNabendu Sekhar en-aut-sei=Chatterjee en-aut-mei=Nabendu Sekhar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BhattacharyaSushmita en-aut-sei=Bhattacharya en-aut-mei=Sushmita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=2 en-affil=Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=3 en-affil=Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=4 en-affil=Division of General Medicine, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=5 en-affil=Division of Bacteriology, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=6 en-affil=Division of Bacteriology, ICMR- National Institute for Research in Bacterial Infections 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, ICMR- National Institute for Research in Bacterial Infections kn-affil= affil-num=9 en-affil=Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections kn-affil= en-keyword=V. cholerae kn-keyword=V. cholerae en-keyword=Sodium butyrate kn-keyword=Sodium butyrate en-keyword=Tetracycline kn-keyword=Tetracycline en-keyword=Synergy kn-keyword=Synergy en-keyword=Antibiotic adjuvant kn-keyword=Antibiotic adjuvant 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=2026 dt-pub=20260201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Does Human Depopulation Reduce Resource Consumption??Evidence from Anthropocene Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Humanityfs deepening strain on Earth systems has sparked widespread discussion of an gAnthropocene crisis,h often attributed to overpopulation. This raises the question: if overpopulation underpins the crisis, does its resolution lie in depopulation? Here, we examine the effects of Japanfs ongoing depopulation on the nexus of population, economy, cropland use, food, water, and energy. We take a systematic Bayesian approach to examine changes in the strength and direction of causality among these variables and explore plausible future pathways under Shared Socioeconomic Pathway (SSP) scenarios. We find that, while depopulation has led to reductions in resource demand, notably for water and energy, impacts on the food system are more complex due to interdependencies with economic and other factors beyond population change. In conclusion, we argue that it will take longer than predicted for depopulation dividends to materialize at a scale that could meaningfully contribute to addressing the crisis, and that proactive efforts to reshape consumption patterns and restructure economic systems, from a model predicated on perpetual growth to one oriented toward sufficiency, are necessary to capitalize on the potential dividends offered by this demographic shift. en-copyright= kn-copyright= en-aut-name=BarrahmouneAnass en-aut-sei=Barrahmoune en-aut-mei=Anass kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatanlePeter en-aut-sei=Matanle en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimJiyoung en-aut-sei=Kim en-aut-mei=Jiyoung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Humanities and Social Sciences, Faculty of Economics, Okayama University kn-affil= affil-num=2 en-affil=School of East Asian Studies, The University of Sheffield kn-affil= affil-num=3 en-affil=Graduate School of Humanities and Social Sciences, Faculty of Economics, Okayama University kn-affil= en-keyword=Anthropocene crisis kn-keyword=Anthropocene crisis en-keyword=Depopulation dividend kn-keyword=Depopulation dividend en-keyword=Population kn-keyword=Population en-keyword=Overpopulation kn-keyword=Overpopulation en-keyword=Resource nexus kn-keyword=Resource nexus en-keyword=Bayesian analysis kn-keyword=Bayesian analysis END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=RP106917 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dorsoventral-mediated Shh induction is required for axolotl limb regeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Axolotls (Ambystoma mexicanum) exhibit a remarkable ability to regenerate limbs. Classical experiments have suggested that contact between cells derived from distinct orientations?dorsal, ventral, anterior, and posterior?within the regenerating blastema is necessary for accurate limb pattern formation. However, the molecular basis for this requirement has remained largely unknown. Here, we demonstrate that both dorsal and ventral tissues are required for limb formation via induction of Shh expression, which plays a crucial role in limb patterning. Using the accessory limb model, we induced position-specific blastemas lacking cells derived from a single orientation (anterior, posterior, dorsal, or ventral). Limb patterning occurred only in blastemas containing both dorsal- and ventral-derived cells. We further observed that Shh expression requires dorsoventral contact within a blastema, highlighting the necessity of dorsoventral contact for inducing Shh expression. Additionally, we identified WNT10B and FGF2 as dorsal- and ventral-mediated signals, respectively, that create the inductive environment for Shh expression. Our findings clarify the role of dorsal and ventral cells in inducing Shh, a mechanism that has rarely been studied in the context of limb regeneration and pattern formation. This model provides new insights into how cells with different positional identities drive the regeneration process. en-copyright= kn-copyright= en-aut-name=YamamotoSakiya en-aut-sei=Yamamoto en-aut-mei=Sakiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FurukawaSaya en-aut-sei=Furukawa en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiAyaka en-aut-sei=Ohashi en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamadaMayuko en-aut-sei=Hamada en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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= affil-num=5 en-affil=Okayama University, Graduate School of Environmental, Life, Natural Science and Technology kn-affil= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=12 article-no= start-page=5742 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250615 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Specific Heat-Killed Lactic Acid Bacteria Enhance Mucosal Aminopeptidase N Activity in the Small Intestine of Aged Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aminopeptidase N (APN), an enzyme expressed in the small intestinal mucosa, is involved in dietary protein digestion. Previous studies have shown that oral administration of fermented milk containing lactic acid bacteria (LAB) enhances mucosal APN activity in young mice. This study aimed to investigate whether LAB strains stimulate mucosal APN activity in aged mice and to evaluate its relevance to age-related changes in body composition. The underlying molecular mechanisms were also explored in vitro. Experiment 1: Aged C57BL/6J mice were fed diets supplemented with heat-killed LAB strains?Enterococcus faecalis OU-23 (EF), Leuconostoc mesenteroides OU-03 (LM), or Lactiplantibacillus plantarum SNK12 (LP). Compared to the aged Control group, the ileal APN activity was significantly higher in the LP group. LP administration also elevated serum Gla-osteocalcin levels and decreased serum CTX-1 levels. Experiment 2: IEC-6 cells were co-cultured with LP that had been treated with RNase, DNase, or lysozyme. APN activity was significantly lower in cells co-cultured with DNase- or lysozyme-treated LP compared to those co-cultured with untreated LP. A specific LAB strain may enhance mucosal APN activity in the aged intestine, potentially contributing to improved bone metabolism. This effect may be mediated by bacterial DNA and peptidoglycan. en-copyright= kn-copyright= en-aut-name=TsurutaTakeshi en-aut-sei=Tsuruta en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WakisakaMami en-aut-sei=Wakisaka en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeTakumi en-aut-sei=Watanabe en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishijimaAoi en-aut-sei=Nishijima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaAkihito en-aut-sei=Ikeda en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TeraokaMao en-aut-sei=Teraoka en-aut-mei=Mao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WangTianyang en-aut-sei=Wang en-aut-mei=Tianyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChenKuiyi en-aut-sei=Chen en-aut-mei=Kuiyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishinoNaoki en-aut-sei=Nishino en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Bio-Lab Co., Ltd. kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=aging kn-keyword=aging en-keyword=aminopeptidase N kn-keyword=aminopeptidase N en-keyword=bone metabolism kn-keyword=bone metabolism en-keyword=lactic acid bacteria kn-keyword=lactic acid bacteria en-keyword=small intestine kn-keyword=small intestine END start-ver=1.4 cd-journal=joma no-vol=123 cd-vols= no-issue=6 article-no= start-page=e2518136123 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A nuclear CobW/WW-domain factor represses the CO2-concentrating mechanism in the green alga Chlamydomonas reinhardtii en-subtitle= kn-subtitle= en-abstract= kn-abstract=Microalgae induce a CO2-concentrating mechanism (CCM) to maintain photosynthesis when CO2 is limited. Because this system consumes a substantial portion of photosynthetically generated ATP, its suppression when CO2 levels rise is critical for energy balance, yet the underlying mechanism remains unclear. Here, we identify a nuclear repressor of the CCM in the green alga Chlamydomonas reinhardtii. A pull-down screen for interacting partners of the master activator CCM1/CIA5 revealed an uncharacterized protein that tightly associates with CCM1. This protein, CCM1-binding protein 1 (CBP1), combines a CobW/CobW_C GTP-binding metallochaperone module with a WW-domain characteristic of protein?protein interactions. CBP1 colocalizes and interacts with CCM1 in the nucleus regardless of CO2 conditions. Disruption of CBP1 does not affect growth or CCM induction under CO2 limitation but derepresses 27 of 41 CCM1-dependent low-CO2 inducible genes under high-CO2 conditions. These include the periplasmic and intracellular carbonic anhydrases (CAH1 and LCIB) and inorganic carbon transporters/channels (LCIA, LCI1, BST1, and BST3). Consistently, cbp1 mutants accumulate CAH1 and LCIB proteins and exhibit 40% higher inorganic carbon affinity under high-CO2 conditions; this phenotype is rescued by CBP1 complementation or by acetazolamide treatment. Crucially, cbp1 mutants exhibit significant growth delays under high-CO2 conditions, especially when light is limiting, providing direct evidence that CBP1-mediated repression is essential for energy conservation. Thus, CBP1 prevents unnecessary CCM activity when CO2 is abundant, acting upstream of both transporter/channel and carbonic anhydrase modules. Our findings suggest a regulatory mechanism potentially linking zinc-dependent protein chemistry to CCM gene repression, providing insights into energy-efficient CO2 sensing in aquatic photosynthetic organisms. en-copyright= kn-copyright= en-aut-name=ShimamuraDaisuke en-aut-sei=Shimamura en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasudaJunko en-aut-sei=Yasuda en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamaharaYosuke en-aut-sei=Yamahara en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakanoHirobumi en-aut-sei=Nakano en-aut-mei=Hirobumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OzawaShin-Ichiro en-aut-sei=Ozawa en-aut-mei=Shin-Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokutsuRyutaro en-aut-sei=Tokutsu en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamagamiAyumi en-aut-sei=Yamagami en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsushitaTomonao en-aut-sei=Matsushita en-aut-mei=Tomonao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakahashiYuichiro en-aut-sei=Takahashi en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakanoTakeshi en-aut-sei=Nakano en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FukuzawaHideya en-aut-sei=Fukuzawa en-aut-mei=Hideya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamanoTakashi en-aut-sei=Yamano en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=2 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=3 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Science, Division of Biological Sciences, Kyoto University kn-affil= affil-num=7 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=8 en-affil=Graduate School of Science, Division of Biological Sciences, Kyoto University kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=11 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= affil-num=12 en-affil=Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University kn-affil= en-keyword=carbonic anhydrase kn-keyword=carbonic anhydrase en-keyword=Chlamydomonas reinhardtii kn-keyword=Chlamydomonas reinhardtii en-keyword=CO2-concentrating mechanism kn-keyword=CO2-concentrating mechanism en-keyword=photosynthesis kn-keyword=photosynthesis en-keyword=pyrenoid kn-keyword=pyrenoid 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=2026 dt-pub=20260202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pediatric autologous peripheral blood stem cell collection without heparin using a highly concentrated sodium citrate anticoagulant: A retrospective comparison with standard ACD-A en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Heparin combined with sodium citrate has been used in leukocytapheresis for pediatric patients. Since 2022, we have performed leukocytapheresis using a highly concentrated sodium citrate solution (HSC, 5.32%) instead of acid citrate dextrose solution A (ACD-A). We conducted this study to determine whether HSC use reduces run time and the total amount of anticoagulant solution in children.
Study Design and Methods: We retrospectively analyzed data from consecutive autologous peripheral blood stem cell harvests (auto-PBSCHs) between June 2012 and May 2025, including patient characteristics, mobilization methods, protocol used, anticoagulant type, run time, total anticoagulant solution volume, and collection efficiency.
Results: Auto-PBSCH was performed using the mononuclear cell collection (MNC) protocol in 28 procedures and the continuous MNC protocol in 20 procedures. ACD-A was used in 35 procedures and HSC in 13. The run time was significantly shorter (204 [range, 117?302] vs. 157?min [range, 103?227], p?=?.02) in the HSC group and also confirmed in multivariable regression analysis (coefficient, ?55.6; 95% confidence interval, ?106.2 to ?5.04; p?=?.03). In a subgroup analysis of cMNC procedures, CD34+ collection efficiency showed a strong negative correlation with the proportion of run time devoted to establishing the initial interface (r?=??.73, p?=?.0003).
Conclusion: Delays in establishing the initial interface can reduce the duration of the effective MNC collection phase and may negatively affect collection efficiency. Careful attention to the initial interface phase is therefore warranted when using HSC. en-copyright= kn-copyright= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkeuchiKazuhiro en-aut-sei=Ikeuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShimonoJoji en-aut-sei=Shimono en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurakamiHiroyuki en-aut-sei=Murakami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Okayama University Hospital kn-affil= en-keyword=acid citrate dextrose solution kn-keyword=acid citrate dextrose solution en-keyword=autologous kn-keyword=autologous en-keyword=continuous mononuclear cell collection kn-keyword=continuous mononuclear cell collection en-keyword=highly concentrated sodium kn-keyword=highly concentrated sodium en-keyword=pediatric kn-keyword=pediatric en-keyword=peripheral blood stem cells kn-keyword=peripheral blood stem cells END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mycobacterium mageritense-associated refractory cutaneous infection and lymphadenitis in an immunocompetent adult: insights from genomic sequencing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Nontuberculous mycobacteria are increasingly recognized as causes of chronic and refractory skin and soft tissue infections, even in individuals without immunodeficiency. Among them, Mycobacterium mageritense is a rare, rapidly growing species that can lead to persistent lesions requiring prolonged antimicrobial therapy. Reports of M. mageritense infections involving both the skin and regional lymph nodes are limited, and this case adds new clinical and genomic insights.
Case presentation A 48-year-old previously healthy man presented with a slowly enlarging cutaneous lesion on his lower leg and ipsilateral inguinal lymphadenitis. Empirical antibacterial therapy with ƒÀ-lactams and macrolides was ineffective. Wound cultures subsequently grew M. mageritense, confirmed by whole-genome sequencing. Several antimicrobial regimens were attempted, and the final successful therapy consisted of oral levofloxacin and minocycline for 4 months, leading to complete clinical resolution. Genomic analysis identified resistance-related genes, including erm(40), aac(2Œ)-Ib, tet(V), and RbpA, although in vitro minimum inhibitory concentrations showed variable susceptibility. Phylogenetic comparison revealed that the isolate was closely related to previously reported M. mageritense strains from Japan.
Conclusions This case demonstrates that M. mageritense can cause cutaneous infection with secondary lymphadenitis in an immunocompetent host. Accurate species identification using molecular or genomic methods and selection of appropriate combination antibiotic therapy based on susceptibility testing are crucial for successful management of such infections. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawakamiYoshio en-aut-sei=Kawakami en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuuraYoshiko en-aut-sei=Matsuura en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiharaSatoru en-aut-sei=Sugihara en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MuenrayaPoowadon en-aut-sei=Muenraya en-aut-mei=Poowadon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Konohana Dermatology Clinic kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Genome sequence kn-keyword=Genome sequence en-keyword=Lymphadenitis kn-keyword=Lymphadenitis en-keyword=Mycobacterium mageritense kn-keyword=Mycobacterium mageritense en-keyword=Skin and soft tissue infections kn-keyword=Skin and soft tissue infections en-keyword=Rapidly growing mycobacteria kn-keyword=Rapidly growing mycobacteria END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=e102426 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Central Serous Chorioretinopathy in Parallel With Onset and Relapses of Minimal Change Nephrotic Syndrome: A 28-Year Case Follow-Up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Central serous chorioretinopathy is an idiopathic disease that manifests as one or several localized, small, dome-shaped serous retinal detachments on fundus examination. The pathophysiology involves fluid leakage from the choroidal capillaries, known as the choriocapillaris, into the subretinal space through sites of damage in the retinal pigment epithelium. This case report discusses the underlying causes of central serous chorioretinopathy-like findings in minimal change nephrotic syndrome.

The patient was a 33-year-old woman who developed nephrotic syndrome that was confirmed to be minimal change disease by renal biopsy. She experienced two major relapses of nephrotic syndrome at the ages of 36 and 41 years. She also had a minor relapse at the age of 37 years, five months after the first major relapse at the age of 36 years, as well as four additional minor relapses at the ages of 44, 46, 50, and 51 years. The onset of central serous chorioretinopathy-like manifestations, which were localized to the left eye, occurred three months after the initial onset of nephrotic syndrome at the age of 33 years. Two subsequent episodes of relapse of central serous chorioretinopathy-like manifestations were observed in both eyes at intervals of five months and one month, respectively, after major relapses of nephrotic syndrome at the ages of 36 and 41 years. Thereafter, she did not develop further central serous chorioretinopathy-like manifestations.

She discontinued oral prednisolone at the age of 54 years and experienced no further relapses of nephrotic syndrome through her latest visit at the age of 61 years. She maintained normal renal function and good visual acuity in both eyes. The long-term, consistent temporal association between episodes of central serous chorioretinopathy and the onset and relapses of minimal change nephrotic syndrome is strongly supported by longitudinal clinical observations spanning 28 years. This parallel course suggests a possible shared pathophysiological mechanism or common triggering factors underlying both diseases. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=central serous chorioretinopathy kn-keyword=central serous chorioretinopathy en-keyword=corticosteroid kn-keyword=corticosteroid en-keyword=cyclosporine kn-keyword=cyclosporine en-keyword=fluorescein angiography kn-keyword=fluorescein angiography en-keyword=minimal change disease kn-keyword=minimal change disease en-keyword=minimal change nephrotic syndrome kn-keyword=minimal change nephrotic syndrome en-keyword=photoreceptor ellipsoid zone kn-keyword=photoreceptor ellipsoid zone en-keyword=renal biopsy kn-keyword=renal biopsy en-keyword=steroid-induced retinal pigment epitheliopathy kn-keyword=steroid-induced retinal pigment epitheliopathy en-keyword=steroid pulse therapy kn-keyword=steroid pulse therapy END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SPRED2 suppresses the stemness of hepatocellular carcinoma through the p53/miR-506-3p/KLF4 pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: We previously reported that endogenous Sprouty-related, EVH1 domain-containing protein 2 (SPRED2), an inhibitor of the Ras/Raf/ERK-MAPK pathway, controls hepatocellular carcinoma (HCC) cell stemness by downregulating the expression of pluripotency factors, such as Nanog, c-Myc, and KLF4, in an ERK-dependent fashion. However, the exact mechanisms by which SPRED2 regulates HCC cell stemness have not been established.
Methods: Three human HCC cell lines [HepG2 (parental and SPRED2-deficient), HLE, and Hep3B] were used. Cells were transfected to downregulate or overexpress proteins. Western blot and RT-qPCR were used to evaluate the level of protein and mRNA expression. Co-immunoprecipitation and ChIP-qPCR were used to examine protein-protein interactions and the activation of gene transcription. Clinical HCC tissues were also used to validate in vitro data.
Results: KLF4 was identified as the major pluripotency factor responsible for SPRED2-mediated downregulation of HCC cell stemness and KLF4 expression was regulated by miR-506-3p. SPRED2 formed a protein complex with the tumor suppressor (p53) and upregulated miR-506 gene transcription by binding to the promoter region, resulting in subsequent downregulation of KLF4 mRNA expression. There was a negative correlation between KLF4 expression and miR-506-3p and a positive correlation between miR-506-3p expression and SPRED2 in human HCC samples, highlighting the relevance of the study findings.
Conclusions: The current study revealed a novel SPRED2/p53/miR-506-3p/KLF4 axis through which SPRED2 contributes to the suppression of HCC cell stemness and provides a potential new target to prevent HCC progression. en-copyright= kn-copyright= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoSachio en-aut-sei=Ito en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Moh-Moh-AungAye en-aut-sei=Moh-Moh-Aung en-aut-mei=Aye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangTianyi en-aut-sei=Wang en-aut-mei=Tianyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=SPRED2 kn-keyword=SPRED2 en-keyword=p53 kn-keyword=p53 en-keyword=KLF4 kn-keyword=KLF4 en-keyword=miR-506-3p kn-keyword=miR-506-3p en-keyword=stemness kn-keyword=stemness END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=1 article-no= start-page=10 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bridging the Gap Between Static Histology and Dynamic Organ-on-a-Chip Models en-subtitle= kn-subtitle= en-abstract= kn-abstract=For more than a century, pathology has served as a cornerstone of modern medicine, relying primarily on static microscopic assessment of tissue morphology?such as H&E staining?which remains the ggold standardh for disease diagnosis. However, this conventional paradigm provides only a snapshot of disease states and often fails to capture their dynamic evolution and complex functional mechanisms. Moreover, animal models are constrained by marked interspecies differences, creating a persistent gap in translational research. To overcome these limitations, we propose the concept of New Pathophysiology, a research framework that transcends purely morphological descriptions and aims to resolve functional dynamics in real time. This approach integrates Organ-on-a-Chip (OOC) technology, multi-omics analyses, and artificial intelligence to reconstruct the entire course of disease initiation and to enable personalized medicine. In this review, we first outline the foundations and limitations of traditional pathology and animal models. We then systematically summarize more than one hundred existing OOC disease models across multiple organs?including the kidney, liver, and brain. Finally, we elaborate on how OOC technologies are reshaping the study of key pathological processes such as inflammation, metabolic dysregulation, and fibrosis by converting them into dynamic, mechanistic disease models, and we propose future perspectives in the field. This review adopts a relatively uncommon classification strategy based on pathological mechanisms (mechanism-based), rather than organ-based categorization, allowing readers to recognize shared principles underlying different diseases. Moreover, the focus of this work is not on emphasizing iteration or replacement of existing approaches, but on preserving past achievements from a historical perspective, with an emphasis on overcoming current limitations and enabling new advances. en-copyright= kn-copyright= en-aut-name=WangZheyi en-aut-sei=Wang en-aut-mei=Zheyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=new pathophysiology kn-keyword=new pathophysiology en-keyword=organ-on-a-chip/OOC kn-keyword=organ-on-a-chip/OOC en-keyword=dynamic disease modeling kn-keyword=dynamic disease modeling en-keyword=histopathology kn-keyword=histopathology en-keyword=large-model analysis kn-keyword=large-model analysis en-keyword=personalized medicine kn-keyword=personalized medicine END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=1 article-no= start-page=116781 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunopeptidomics combined with full-length transcriptomics uncovers diverse neoantigens en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neoantigens are crucial for antitumor immunity and immune checkpoint inhibitor (ICI) efficacy by triggering strong immune responses. However, conventional methods for identifying neoantigens, such as whole-exon sequencing and short-read RNA sequencing (RNA-seq), appear to be insufficient, and the tumor mutational burden cannot sufficiently predict ICI efficacy. In this study, we employed a proteogenomic approach using long-read RNA-seq with Pacific Biosciences Single-Molecule Real-Time Sequencing technology to analyze full-length transcripts in combination with the human leukocyte antigen ligandome. As a result, many neoantigen candidates were identified, which were unregistered in a comprehensive database, including those from non-coding regions. Additionally, we validated the responses of specific T cell receptors (TCRs) to these candidates and identified several pairs of TCRs and neoantigens. These findings highlight the presence of more diverse neoantigens than expected that cannot be identified by conventional methods. en-copyright= kn-copyright= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeTomofumi en-aut-sei=Watanabe en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokitaSerina en-aut-sei=Tokita en-aut-mei=Serina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KawaseKatsushige en-aut-sei=Kawase en-aut-mei=Katsushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakanoYuka en-aut-sei=Takano en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ThuYin Min en-aut-sei=Thu en-aut-mei=Yin Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SuzukiYuta en-aut-sei=Suzuki en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OwaChie en-aut-sei=Owa en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ZhouWenhao en-aut-sei=Zhou en-aut-mei=Wenhao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KochinVitaly en-aut-sei=Kochin en-aut-mei=Vitaly kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UenoToshihide en-aut-sei=Ueno en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KojimaShinya en-aut-sei=Kojima en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OhnumaTakehiro en-aut-sei=Ohnuma en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MatsuzawaTakamitsu en-aut-sei=Matsuzawa en-aut-mei=Takamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KawaharaYu en-aut-sei=Kawahara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamashitaKazuo en-aut-sei=Yamashita en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=LinJason en-aut-sei=Lin en-aut-mei=Jason kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KosekiJun en-aut-sei=Koseki en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NishikawaHiroyoshi en-aut-sei=Nishikawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 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=25 ORCID= en-aut-name=KatoNaoya en-aut-sei=Kato en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ShimamuraTeppei en-aut-sei=Shimamura en-aut-mei=Teppei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MorishitaShinichi en-aut-sei=Morishita en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 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=29 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=TorigoeToshihiko en-aut-sei=Torigoe en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=KanasekiTakayuki en-aut-sei=Kanaseki en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 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=34 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Division of Cancer Immunology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=4 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=6 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Computational Biology and Medical Sciences, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Computational Biology and Medical Sciences, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Immunology, Nagoya University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=15 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=16 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=17 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=18 en-affil=Department of Dermatology, Kumamoto Kenhoku Hospital kn-affil= affil-num=19 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=21 en-affil=KOTAI Biotechnologies, Inc kn-affil= affil-num=22 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=23 en-affil=Division of Systems Biology, Nagoya University Graduate School of Medicine kn-affil= affil-num=24 en-affil=Department of Immunology, Nagoya University Graduate School of Medicine kn-affil= affil-num=25 en-affil=Department of Urology, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil=Department of Gastroenterology, Graduate School of Medicine, Chiba University kn-affil= affil-num=27 en-affil=Division of Systems Biology, Nagoya University Graduate School of Medicine kn-affil= affil-num=28 en-affil=Department of Computational Biology and Medical Sciences, The University of Tokyo kn-affil= affil-num=29 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=30 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=31 en-affil= kn-affil= affil-num=32 en-affil=Division of Cancer Immunology, Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=33 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=34 en-affil=Department of Tumor Microenvironment, Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cancer immunology kn-keyword=cancer immunology en-keyword=neoantigen kn-keyword=neoantigen en-keyword=long-read RNA sequencing kn-keyword=long-read RNA sequencing en-keyword=HLA ligandome kn-keyword=HLA ligandome en-keyword=single-cell RNA sequencing kn-keyword=single-cell RNA sequencing en-keyword=single-cell TCR sequencing kn-keyword=single-cell TCR sequencing en-keyword=exhausted T cell kn-keyword=exhausted T cell END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=12 article-no= start-page=110594 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endoscopic features of oral and pharyngolaryngeal papillomas and their role in distinguishing squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND
Oral and pharyngolaryngeal papillomas are occasionally detected during esophagogastroduodenoscopy. However, their endoscopic features have not been sufficiently investigated.
AIM
To distinguish oral and pharyngolaryngeal papillomas from elevated squamous carcinomas, this study examined their endoscopic features.
METHODS
Forty-seven patients with oral or pharyngeal papilloma participated in this study. The endoscopic characteristics of papillomas were identified by focusing on narrowband and blue laser imaging representations.
RESULTS
Papillomas were classified into three patterns based on their endoscopic features: Salmon roe-like polyps, polyps without capillary transparency, and pinecone-like polyps, with salmon roe-like polyps most prevalent (48.9%). We subsequently analyzed features differentiating papillomas and squamous cell carcinomas in the same region and found that squamous cell carcinomas exhibited at least one of the following three features: Uneven or absent lobulated structure, irregular morphology of capillaries, and coexistence of flat lesions. In contrast, papillomas displayed a uniform lobulated structure, homogeneous or non-visible capillaries, and an absence of flat components. When any of these characteristics were present, two endoscopic specialists evaluated the lesions for the diagnosis of squamous cell carcinoma, with sensitivities of 100% and 97.6% and specificities of 68.9% and 93.3%.
CONCLUSION
Understanding distinct endoscopic patterns of oropharyngeal papillomas and squamous cell carcinomas provides valuable guidance to endoscopists performing esophagogastroduodenoscopy. 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=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=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=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 Pathology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= 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 Practical Gastrointestinal Endoscopy, 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=Esophagogastroduodenoscopy kn-keyword=Esophagogastroduodenoscopy en-keyword=Human papillomavirus kn-keyword=Human papillomavirus en-keyword=Laryngeal polyp kn-keyword=Laryngeal polyp en-keyword=Papilloma kn-keyword=Papilloma en-keyword=Pharyngeal polyp kn-keyword=Pharyngeal polyp 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=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multi-step mechanisms of early phospholipid hydrolysis and mineralisation unveiled through combined quantum chemical calculations and experimental analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Phospholipids play key roles in bone formation, with phosphatidylserine (PS) reportedly inducing more rapid mineralisation than phosphatidylcholine (PC); however, the underlying mechanisms remains unclear. This study investigated PS and PC mineralisation using experimental methods and computational chemistry. The stationary points in the potential energy surfaces of the reactions were preliminarily found using a neural network potential (PreFerred Potential in Matlantis) capable of predicting the interaction energies for arbitrary combinations of atoms, and then refined through density functional theory calculations (Gaussian16, at the B3LYP/6-31G(d,p) level of theory). When hydrolysis reactions were assumed to be the initial step in the mineralisation of phospholipids, the results were consistent with empirical analysis. PS was found to be more easily hydrolised than PC, primarily owing to the presence of a labile proton in the NH3+ group of serine that facilitates proton transfer, enhancing hydrolysis of PS at lower energy thresholds. Specifically, when a single phospholipid was considered, three distinct hydrolysis routes were identified: between serine (or choline) and phosphate, between glycerol and phosphate, and between an aliphatic carbon chain and the glycerol backbone. In particular, the initial steps of hydrolysis involved the formation of a pentavalent phosphate intermediate. When calculations were performed with two adjacent phospholipid molecules, the loosely bound proton (H+) in the NH3+ group could be readily transferred either to the P?O bond linking serine to the phosphate group; or to the P?O bond connecting the phosphate to glycerol in a neighboring PS6 molecule. These findings reveal the important roles of serine NH3+ in facilitating hydrolysis of PS, and provide insights for designing novel molecules to accelerate bone regeneration. en-copyright= kn-copyright= en-aut-name=ShibataKeisuke en-aut-sei=Shibata en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiotaniTakahumi en-aut-sei=Shiotani en-aut-mei=Takahumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChenYunhao en-aut-sei=Chen en-aut-mei=Yunhao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuriharaReina en-aut-sei=Kurihara en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamaguchiKatsunori en-aut-sei=Yamaguchi en-aut-mei=Katsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KunioshiN?lson en-aut-sei=Kunioshi en-aut-mei=N?lson kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Materials Science, Waseda University kn-affil= affil-num=2 en-affil=Department of Resources and Environmental Engineering, Waseda University kn-affil= affil-num=3 en-affil=Department of Materials Science, Waseda University kn-affil= affil-num=4 en-affil=Department of Resources and Environmental Engineering, Waseda University kn-affil= affil-num=5 en-affil=Department of Resources and Environmental Engineering, Waseda University kn-affil= affil-num=6 en-affil=Department of Advanced International and Information Dentistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Materials Science, Waseda University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=7 article-no= start-page=102730 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of full-time equivalent allocation on the effectiveness of antimicrobial stewardship activities: A multicenter study in Okayama, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Optimized administration of antimicrobial agents is critical for mitigating the emergence of antimicrobial resistance. This study aimed to elucidate the relationship between antimicrobial stewardship (AS) activities and antimicrobial prescription trends and patterns.
Methods: This retrospective, multicenter, longitudinal study was conducted between April 2014 and March 2023 (9-year fiscal period). A structured, questionnaire survey, regarding institutional infrastructure and environmental parameters, service modalities provided by AS activities, resource allocation and systemic support, and data on the use of broad-spectrum antimicrobial agents, was distributed to co-investigators working at seven hospitals in Okayama, Japan. Full-time equivalent (FTE) allocation for each healthcare facility were calculated and subsequently compared among the hospitals. Temporal variations in the proportional distribution of broad-spectrum antimicrobial agents were statistically evaluated using joinpoint regression analysis.
Results: Two hospitals where pharmacists were exclusively dedicated to AS activities and met the recommended FTE allocation showed a statistically significant reduction in the proportion of broad-spectrum antibiotic administration, with average annual percentage changes of ?8.0 % (95 % confidence interval [CI]: ?10.5 to ?5.8) and ?3.1 % (95 % CI: ?5.5 to ?0.7), respectively. In contrast, two other hospitals with full-time AS members but insufficient FTE allocation exhibited inconsistent and statistically nonuniform trends. The remaining three healthcare institutions with poorly resourced AS teams demonstrated no statistically significant trends in their broad-spectrum antimicrobial prescriptions.
Conclusion: Our findings uncovered that hospitals with adequate FTE staffing metrics for AS activities exhibited statistically significant downward trends in the consumption of broad-spectrum antimicrobial agents. en-copyright= kn-copyright= en-aut-name=KajitaShiho en-aut-sei=Kajita en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkitaAtsushi en-aut-sei=Okita en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HarukiYuto en-aut-sei=Haruki en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaHaruto en-aut-sei=Yamada en-aut-mei=Haruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueYasurou en-aut-sei=Inoue en-aut-mei=Yasurou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashionnaTsukasa en-aut-sei=Higashionna en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatouKana en-aut-sei=Satou en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TorigoeFumihiro en-aut-sei=Torigoe en-aut-mei=Fumihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwamotoShinobu en-aut-sei=Iwamoto en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshidaMika en-aut-sei=Yoshida en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamaneYumiko en-aut-sei=Yamane en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KenmotsuHiroki en-aut-sei=Kenmotsu en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SugimuraSatoru en-aut-sei=Sugimura en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraYutaka en-aut-sei=Fujiwara en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IkedaFusao en-aut-sei=Ikeda en-aut-mei=Fusao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YoshidaChikamasa en-aut-sei=Yoshida en-aut-mei=Chikamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AndouShinichirou en-aut-sei=Andou en-aut-mei=Shinichirou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SuwakiToshimitsu en-aut-sei=Suwaki en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Antimicrobial Stewardship Team, Okayama City Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Setouchi City Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Tsuyama Chuo Hospital kn-affil= affil-num=5 en-affil=Antimicrobial Stewardship Team, Okayama City Hospital kn-affil= affil-num=6 en-affil=Antimicrobial Stewardship Team, Okayama City Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Pharmacy, Kurashiki Central Hospital kn-affil= affil-num=9 en-affil=Division of Pharmacy, Kurashiki Central Hospital kn-affil= affil-num=10 en-affil=Division of Pharmacy, Okayama Kyoritsu Hospital kn-affil= affil-num=11 en-affil=Infection Control Team, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=12 en-affil=Infection Control Team, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=13 en-affil=Division of Pharmacy, Okayama Saiseikai Hospital kn-affil= affil-num=14 en-affil=Department of Internal Medicine, Okayama Kyoritsu Hospital kn-affil= affil-num=15 en-affil=Infection Control Team, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=16 en-affil=Department of Hepatology, Okayama Saiseikai Hospital kn-affil= affil-num=17 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Infection Control Team, Okayama City Hospital kn-affil= affil-num=19 en-affil=Infection Control Team, Okayama City Hospital kn-affil= affil-num=20 en-affil=Infection Control Team, Okayama City Hospital kn-affil= en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=Antimicrobial stewardship kn-keyword=Antimicrobial stewardship en-keyword=Full-time equivalent kn-keyword=Full-time equivalent en-keyword=Infection prevention and control kn-keyword=Infection prevention and control en-keyword=Trend analysis kn-keyword=Trend analysis END start-ver=1.4 cd-journal=joma no-vol=145 cd-vols= no-issue= article-no= start-page=105021 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Assessing the role of folate syntrophy and folate cross-feeding in the pathobiology of infectious-inflamed milieu caused by Fusobacterium nucleatum en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diet and nutrition affect almost every biological process, including multiple chronic diseases, diabetes, and some cancers. However, there are still significant gaps in our understanding of the importance of nutrition and healthy diets in syntrophy with respect to cross-feeding of the microbe-microbe and the microbe-host in the pathobiology of the infectious-inflamed intestinal milieu caused by anaerobic opportunistic bacteria such as Fusobacterium nucleatum (F. nucleatum). We examined the immune outcomes of three-member folate syntrophy and cross-feeding between F. nucleatum bacteria, endogenous folate-producing gut bacteria, and host cells at the host-pathogen interface using a triple co-culture model. T84, THP-1, and Huh7 cells were inoculated with F. nucleatum for 6 h in regular DMEM, DMEM with 9.5 ƒÊM folic acid, or with/without a mixture of Bifidobacterium longum subsp. infantis (B. infantis) and Escherichia coli Nissle 1917 (EcN). Cytokine secretion, cometabolite levels (ammonia, indoles), cell viability, and barrier integrity were assessed. F. nucleatum-induced folate depletion was associated with increased IL-1ƒÀ and IL-6 and decreased IL-22, along with reduced transepithelial electrical resistance (TEER) and cell viability in T84 cells. Folate supplementation mitigated these effects. The mixture of B. infantis and EcN reduced F. nucleatum-induced pro-inflammatory cytokines, increased IL-22, and improved TEER and cell viability. These protective effects were enhanced by the addition of folate. F. nucleatum also elevated ammonia and reduced indoles, effects reversed by B. infantis and EcN. In addition to the intrinsic pathogenicity of harmful bacteria, folate deprivation, microbe?microbe folate syntrophy, and microbe?host folate cross-feeding contribute to the pathobiology of anaerobic opportunistic bacteria and influence the physiological fate of host cells. A combination of B. infantis and EcN modulates the infectious-inflamed interface through a cytoprotective effect and mechanical competitive extrusion of pathogenic F. nucleatum. These results provide potential insights into the mechanisms of early-onset colorectal cancer, and evidently, require future studies using patient-derived organoids and in vivo systems to improve clinical relevance. en-copyright= kn-copyright= en-aut-name=GhadimiDarab en-aut-sei=Ghadimi en-aut-mei=Darab kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Bl?merSophia en-aut-sei=Bl?mer en-aut-mei=Sophia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=?ahin KayaAysel en-aut-sei=?ahin Kaya en-aut-mei=Aysel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Kr?gerSandra en-aut-sei=Kr?ger en-aut-mei=Sandra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=R?ckenChristoph en-aut-sei=R?cken en-aut-mei=Christoph kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Sch?ferHeiner en-aut-sei=Sch?fer en-aut-mei=Heiner kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsuzakiShigenobu en-aut-sei=Matsuzaki en-aut-mei=Shigenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BockelmannWilhelm en-aut-sei=Bockelmann en-aut-mei=Wilhelm kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= affil-num=2 en-affil=Faculty of Medicine, Christian-Albrechts-University of Kiel kn-affil= affil-num=3 en-affil=Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University kn-affil= affil-num=4 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=5 en-affil=Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein kn-affil= affil-num=6 en-affil=Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel kn-affil= affil-num=7 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University kn-affil= affil-num=9 en-affil=Department of Microbiology and Biotechnology, Max Rubner-Institut kn-affil= en-keyword=Nutrition kn-keyword=Nutrition en-keyword=Metaflammation kn-keyword=Metaflammation en-keyword=Folate kn-keyword=Folate en-keyword=Cytokines kn-keyword=Cytokines en-keyword=Infection kn-keyword=Infection en-keyword=Host cells kn-keyword=Host cells END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=1713471 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=Regulatory considerations for developing phage therapy medicinal products for the treatment of antimicrobial resistant bacterial infections en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, there have been growing expectations that treatment of infections with bacteriophages (phages), viruses which specifically infect bacteria, can be used as a treatment option for antimicrobial resistant bacterial infections. In Europe and the United States, in addition to phage therapy as a form of personalized medicine, development of pre-defined phage therapy medicinal products (PTMPs) is progressing, and clinical trials are underway. From October 2024 to July 2025, the Pharmaceuticals and Medical Devices Agency exchanged opinions on trends and points to consider in drug development of PTMPs used for antimicrobial resistant bacterial infections with external experts. Development of PTMPs for regulatory approval requires quality control strategies, establishment of manufacturing methods, non-clinical evaluations, and clinical trial plans based on the characteristics of the phage. In this document, based on the regulatory and development trends in Europe and the United States, the current considerations on quality, non-clinical evaluation, and clinical trial planning including the Cartagena Act in the development of PTMPs in Japan are summarized. The basic concepts presented here are intended to be applied to antimicrobial resistant bacterial infections targeted by PTMPs but can be mostly applicable to bacterial infections in general. We hope that these findings will further accelerate more active development of PTMPs towards timely patient access to innovative products. en-copyright= kn-copyright= en-aut-name=Fukaya-ShibaAi en-aut-sei=Fukaya-Shiba en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgataAkiko en-aut-sei=Ogata en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuribayashiRyosuke en-aut-sei=Kuribayashi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakuraiAkira en-aut-sei=Sakurai en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiKanako en-aut-sei=Suzuki en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakadamaShunsuke en-aut-sei=Takadama en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimuraJihei en-aut-sei=Nishimura en-aut-mei=Jihei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhgeHiroki en-aut-sei=Ohge en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakeuchiTakamasa en-aut-sei=Takeuchi en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TamakiHideyuki en-aut-sei=Tamaki en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsumotoTetsuya en-aut-sei=Matsumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KigaKotaro en-aut-sei=Kiga en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwanoHidetomo en-aut-sei=Iwano en-aut-mei=Hidetomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=2 en-affil=Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=3 en-affil=Office of Cellular and Tissue-based Products, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=4 en-affil=Office of Cellular and Tissue-based Products, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=5 en-affil=Office of Regulatory Science Coordination, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=6 en-affil=Office of New Drug IV, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=7 en-affil=Office of New Drug IV, Pharmaceuticals and Medical Devices Agency kn-affil= affil-num=8 en-affil=Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Infectious Diseases, Hiroshima University Hospital kn-affil= affil-num=10 en-affil=Pathogen Genomics Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=11 en-affil=Biomanufacturing Process Research Center, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=12 en-affil=Department of Infectious Diseases, International University of Health and Welfare kn-affil= affil-num=13 en-affil=Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=14 en-affil=Laboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary Medicine kn-affil= en-keyword=phage therapy kn-keyword=phage therapy en-keyword=bacteriophage kn-keyword=bacteriophage en-keyword=antimicrobial resistance (AMR) kn-keyword=antimicrobial resistance (AMR) en-keyword=quality considerations kn-keyword=quality considerations en-keyword=non-clinical evaluation kn-keyword=non-clinical evaluation en-keyword=clinical trial plan kn-keyword=clinical trial plan en-keyword=the Cartagena Act kn-keyword=the Cartagena Act END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Addition of human platelet lysate to islet culture medium suppresses islet loss and improves transplantation outcomes en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NoguchiHirofumi en-aut-sei=Noguchi en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Miyagi-ShiohiraChika en-aut-sei=Miyagi-Shiohira en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=SaitohIssei en-aut-sei=Saitoh en-aut-mei=Issei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus kn-affil= affil-num=2 en-affil=Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatric Dentistry, Asahi University School of Dentistry kn-affil= END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=11 article-no= start-page=1023 end-page=1032 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=Bioconversion and Metabolic Fate of the n-1 Polyunsaturated Fatty Acids, 6,9,12,15- Hexadecatetraenoic (C16:4 n-1) and 8,11,14,17- Octadecatetraenoic (C18:4 n-1) Acids, in HepG2 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fish oil contains not only major fatty acids with double bonds at the n-3, n-6, n-7, and n-9 positions but also those with a double bond at the n-1 position, such as 6,9,12,15-hexadecatetraenoic acid (C16:4 n-1; HDTA). However, intracellular bioconversion and metabolic fate of n-1 polyunsaturated fatty acids (PUFA) remain unclear. Therefore, in this study, we aimed to assess the intracellular bioconversion and metabolic fate of HDTA and its metabolite, 8,11,14,17- octadecatetraenoic acid (C18:4 n-1; ODTA), using HepG2 cells. Based on the results of cell viability and cytotoxicity assays for HDTA and ODTA, the concentration of each fatty acid supplemented in the experiments was set at 10 ƒÊM. HepG2 cell culture with HDTA revealed C20:4 n-1 as a new HDTA metabolite, along with previously reported ODTA. Our findings suggest that the HDTA taken up by HepG2 cells undergoes elongation to form ODTA and C20:4 n-1. Following supplementation with HDTA, ODTA, and 5,8,11,14,17-eicosapentaenoic acid (C20:5 n-3; EPA), fatty acids disappeared from the culture medium within 24 h. Notably, the total relative level of HDTA and its metabolites, including ODTA and C20:4 n-1 in HDTA- and ODTA-supplemented cells were significantly lower than the total relative level of EPA and its metabolites, including 7,10,13,16,19-docosapentaenoic acid (C22:5 n-3), C24:6 n-3, and 4,7,10,13,16,19-docosahexaenoic acid (C22:6 n-3) in the EPA-supplemented cells. Except for a portion that was intracellularly elongated, most HDTA was taken up by HepG2 cells and may undergo rapid fatty acid ƒÀ-oxidation. However, RNA-sequencing and real-time polymerase chain reaction analysis revealed no significant changes in fatty acid ƒÀ-oxidation?related gene expression levels in HDTA-supplemented cells. Collectively, these results provide novel insights into the intracellular bioconversion mechanisms and metabolic fate of HDTA and ODTA in HepG2 cells, suggesting that the metabolic fate of n-1 PUFA is distinct from that of common PUFA. en-copyright= kn-copyright= en-aut-name=SugimotoKoki en-aut-sei=Sugimoto en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiguchiHideto en-aut-sei=Nishiguchi en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HosomiRyota en-aut-sei=Hosomi en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanizakiToshifumi en-aut-sei=Tanizaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsushimaTadahiro en-aut-sei=Tsushima en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BabaNaomichi en-aut-sei=Baba en-aut-mei=Naomichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MisawaYoshihisa en-aut-sei=Misawa en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MurakamiYuki en-aut-sei=Murakami en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KandaSeiji en-aut-sei=Kanda en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FukunagaKenji en-aut-sei=Fukunaga en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Faculty of Food and Nutritional Sciences, Toyo University kn-affil= affil-num=2 en-affil=Faculty of Chemistry, Materials, and Bioengineering, Kansai University kn-affil= affil-num=3 en-affil=Faculty of Chemistry, Materials, and Bioengineering, Kansai University kn-affil= affil-num=4 en-affil=Bizen Chemical Co., Ltd. kn-affil= affil-num=5 en-affil=Bizen Chemical Co., Ltd. kn-affil= affil-num=6 en-affil=Bizen Chemical Co., Ltd. kn-affil= affil-num=7 en-affil=Bizen Chemical Co., Ltd. kn-affil= affil-num=8 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hygiene and Public Health, Kansai Medical University kn-affil= affil-num=11 en-affil=Department of Hygiene and Public Health, Kansai Medical University kn-affil= affil-num=12 en-affil=Faculty of Chemistry, Materials, and Bioengineering, Kansai University kn-affil= en-keyword=n-1 polyunsaturated fatty acids kn-keyword=n-1 polyunsaturated fatty acids en-keyword=hexadecatetraenoic acid kn-keyword=hexadecatetraenoic acid en-keyword=octadecatetraenoic acid kn-keyword=octadecatetraenoic acid en-keyword=HepG2 kn-keyword=HepG2 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=20251231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficient resuscitation of early-stage viable but non-culturable cells of Vibrio cholerae using treatment with proteolytic enzymes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vibrio cholerae, the etiological agent of cholera, is ubiquitous in environmental brackish waters. Exposure to low water temperatures induces the bacterium to enter a viable but non-culturable (VBNC) state. In this study, a stepwise decrease in water temperature to 4‹C was found to delay the transition to the non-culturable state compared to an abrupt temperature drop, suggesting that V. cholerae cells partially adapt to low temperatures. V. cholerae VBNC cells maintained at 4‹C gradually lost their ability to revert to a culturable state. However, VBNC cells in the early stage of dormancy were efficiently resuscitated following treatment with proteolytic enzymes, including proteinase K. The abundance of culturable V. cholerae cells in brackish estuarine waters was quantified using the most probable number (MPN)?quantitative polymerase chain reaction (qPCR) method. Although culturable cells were undetectable in samples treated with bovine serum albumin, they were estimated at 93 and 1,500 MPN/mL in two water samples collected on different days and pre-incubated with proteinase K. Similarly, the abundance of Vibrio species increased markedly following treatment with this enzyme. Additionally, cells of Vibrio species were enumerated by the plating method using CHROMagar Vibrio plates. Consistent with the results of the MPN?qPCR method, treatment with proteinase K resulted in over a 100-fold increase in colony formation. Collectively, these findings suggest that treatment with proteinase K is effective for resuscitating and quantifying V. cholerae VBNC cells in environmental water samples. en-copyright= kn-copyright= en-aut-name=MiyoshiShin-ichi en-aut-sei=Miyoshi en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgasawaraMona en-aut-sei=Ogasawara en-aut-mei=Mona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NiwakiShiho en-aut-sei=Niwaki en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugiharaRena en-aut-sei=Sugihara en-aut-mei=Rena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MuzemboBasilua Andre en-aut-sei=Muzembo en-aut-mei=Basilua Andre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImamuraDaisuke en-aut-sei=Imamura en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of 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=Research Institute of Nursing Care for People and Community, University of Hyogo kn-affil= affil-num=6 en-affil=Research Center for Intestinal Health Science, Okayama University kn-affil= en-keyword=Vibrio cholerae kn-keyword=Vibrio cholerae en-keyword=viable but non-culturable kn-keyword=viable but non-culturable en-keyword=VBNC kn-keyword=VBNC en-keyword=protease kn-keyword=protease en-keyword=proteolytic enzyme kn-keyword=proteolytic enzyme END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=29639 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Single cell spatial transcriptomics links Wnt signaling disruption to extracellular matrix development in a cleft palate model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Despite advances in understanding the morphological disruptions that lead to defects in palate formation, the precise perturbations within the signaling microenvironment of palatal clefts remain poorly understood. To explore in greater depth the genomic basis of palatal clefts, we designed and implemented the first single cell spatial RNA-sequencing study in a cleft palate model, utilizing the Pax9?/? murine model at multiple developmental timepoints, which exhibits a consistent cleft palate defect. Visium HD, an emerging platform for true single-cell resolution spatially resolved transcriptomics, was employed using custom bins of 2?~?2 ƒÊm spatial gene expression data. Validation of spatial gene expression was then validated using custom designed Xenium In Situ mRNA spatial profiling and RNAscope Multiplex assays. Functional enrichment analysis revealed a palate cell-specific perturbation in Wnt signaling effector function in tandem with disrupted expression of extracellular matrix genes in developing mesenchyme. As a key step toward laying the framework for identifying key molecular targets these data can be used for translational studies aimed at developing effective therapies for human palatal clefts. en-copyright= kn-copyright= en-aut-name=Pi?aJeremie Oliver en-aut-sei=Pi?a en-aut-mei=Jeremie Oliver kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RajuResmi en-aut-sei=Raju en-aut-mei=Resmi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=StipanoEvan en-aut-sei=Stipano en-aut-mei=Evan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MyoAye Chan en-aut-sei=Myo en-aut-mei=Aye Chan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ChattarajParna en-aut-sei=Chattaraj en-aut-mei=Parna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FurukawaMasae en-aut-sei=Furukawa en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DfSouzaRena N. en-aut-sei=DfSouza en-aut-mei=Rena N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=2 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=3 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=4 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=5 en-affil=Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama University kn-affil= affil-num=7 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=8 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= affil-num=9 en-affil=Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) kn-affil= en-keyword=Spatial biology kn-keyword=Spatial biology en-keyword=Cleft palate kn-keyword=Cleft palate en-keyword=Genomics kn-keyword=Genomics en-keyword=Single cell kn-keyword=Single cell en-keyword=Gene expression kn-keyword=Gene expression en-keyword=Profiling kn-keyword=Profiling en-keyword=Extracellular matrix kn-keyword=Extracellular matrix en-keyword=Wnt kn-keyword=Wnt en-keyword=Transcriptome kn-keyword=Transcriptome END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=12 article-no= start-page=102845 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Whole-genome sequencing and in vitro characterization of a disseminated ST398 Staphylococcus aureus infection: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Staphylococcus aureus potentially causes systemic infections such as disseminated abscesses and bloodstream infections, leading to high mortality rates. We herein describe a case of disseminated muscle abscesses caused by sequence type (ST) 398 methicillin-sensitive S. aureus (MSSA), along with in vitro investigation results for potential pathogenic factors. A 67-year-old healthy woman was admitted to our hospital with complaints of systemic body pain. Blood cultures identified MSSA and contrast-enhanced computed tomography revealed multiple muscle abscesses extending from her neck to her soles. She received antibiotic treatment with intravenous cephazolin and underwent repeated surgical drainage, and was finally discharged. Notably, the MSSA strain exclusively affected her muscle tissues, prompting us to perform genetic analysis to uncover the underlying reason. Short-read genome analysis revealed the isolate to be ST398, harboring chp and scn genes known for immune evasion from human immunity. However, no other known pathogenic factors were identified despite rigorous assays for biofilm formation, surface and cell wall proteins, protease production, and hyaluronidase activity. ST398 S. aureus is commonly isolated from livestock, and her prior experience of being flooded could be related to the disease onset. The present case underscores the possibility of severe ST398 MSSA infections in humans, even in the absence of direct animal exposure. en-copyright= kn-copyright= en-aut-name=SazumiYosuke en-aut-sei=Sazumi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatoAtsushi en-aut-sei=Kato en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuyamaAtsuhito en-aut-sei=Suyama en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KutsunoShoko en-aut-sei=Kutsuno en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HisatsuneJunzo en-aut-sei=Hisatsune en-aut-mei=Junzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugaiMotoyuki en-aut-sei=Sugai en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Bacteriology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=9 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=10 en-affil=Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security kn-affil= affil-num=11 en-affil=Department of Bacteriology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Staphylococcus aureus kn-keyword=Staphylococcus aureus en-keyword=Sequence type 398 kn-keyword=Sequence type 398 en-keyword=Disseminated infection kn-keyword=Disseminated infection en-keyword=Immune evasion cluster gene kn-keyword=Immune evasion cluster gene END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=12 article-no= start-page=102853 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and molecular characteristics of urinary catheter-associated Pseudomonas aeruginosa prostatic infection: A case series of four postoperative nosocomial infections en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pseudomonas aeruginosa is a causative pathogen of nosocomial catheter-associated urinary tract infections (CAUTI), but prostate involvement, including prostatitis and prostatic abscess, is rare. The clinical characteristics of P. aeruginosa-associated CAUTI with prostatic lesions, as well as the contribution of genetic backgrounds remain unclear. We describe four cases of urinary catheter-associated prostatic infection caused by P. aeruginosa following postoperative catheterization. All patients developed fever within 10 days after surgery, and three of the four patients developed bacteremia. Three patients were diagnosed with prostatic abscess by contrast-enhanced computed tomography or magnetic resonance imaging, while one case presented with prostatitis without abscess formation. Prostate-specific antigen levels were elevated over 20 ng/mL in all three measured cases. All patients were treated successfully with prolonged antibiotic therapy (28?39 days) without surgical drainage. Notably, all three abscess cases were successfully managed with fluoroquinolone-based combination therapy, highlighting its potential role in the management of prostatic abscesses. Three of four isolates were submitted for molecular investigations. All isolates harbored exoT and exoY, whereas exoU was absent. Biofilm-associated genes were detected in two cases, but not in the remaining case. Our findings suggested that P. aeruginosa strains carrying T3SS genes (exoT and exoY) potentially develop prostatic infections, independent of biofilm-associated genes. Host and iatrogenic factors, such as catheter manipulation, may play more critical roles in the development of prostatic pathology than strain-specific determinants. Assessment of prostate-specific antigen levels and early imaging may facilitate appropriate diagnosis and effective management when P. aeruginosa is detected as a cause of CAUTI. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SanoTakayuki en-aut-sei=Sano en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KashimotoTakashige en-aut-sei=Kashimoto en-aut-mei=Takashige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= affil-num=1 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University kn-affil= affil-num=3 en-affil=Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Pseudomonas aeruginosa kn-keyword=Pseudomonas aeruginosa en-keyword=Catheter-associated urinary tract infection kn-keyword=Catheter-associated urinary tract infection en-keyword=Prostatic abscess kn-keyword=Prostatic abscess en-keyword=Type III secretion system kn-keyword=Type III secretion system END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=2 article-no= start-page=101548 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cerebellar abscess caused by Cladophialophora bantiana involving an elderly Japanese woman en-subtitle= kn-subtitle= en-abstract= kn-abstract=Phaeohyphomycosis is a rare fungal infection that presents significant challenges in diagnosis and treatment. Herein, we document a case of a cerebellar abscess caused by Cladophialophora bantiana. A 77-year-old woman with type 2 diabetes mellitus and a previous history of diffuse large B-cell lymphoma gradually developed ataxia and was transferred to an emergency department. Head imaging investigations indicated a cerebellar mass and the patient underwent an emergent endoscopic drainage. Although bacterial cultures of the drainage specimen yielded no growth, a dematiaceous fungus was isolated and subsequently identified as C. bantiana through ITS sequencing analysis. The patient received antifungal combination therapy, initially with liposomal amphotericin B and voriconazole, and finally posaconazole and 5-fluorocytosine. Brain abscesses caused by C. bantiana are rarely documented, and an optimal treatment strategy has yet to be established. Given the high fatality rate, an early surgical intervention is crucial for both diagnosis and treatment. The present case was successfully treated with minimally invasive surgical intervention alongside the antifungal combination therapy. en-copyright= kn-copyright= en-aut-name=NakamotoKenta en-aut-sei=Nakamoto en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YokoyamaYukika en-aut-sei=Yokoyama en-aut-mei=Yukika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiranoShuichiro en-aut-sei=Hirano en-aut-mei=Shuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YaguchiTakashi en-aut-sei=Yaguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BanSayaka en-aut-sei=Ban en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeAkira en-aut-sei=Watanabe en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkunobuHiroki en-aut-sei=Okunobu en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SuyamaAtsuhito en-aut-sei=Suyama en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KawaguchiMarina en-aut-sei=Kawaguchi en-aut-mei=Marina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SazumiYousuke en-aut-sei=Sazumi en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=5 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=6 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Division of Clinical Research, Medical Mycology Research Center kn-affil= affil-num=9 en-affil=Division of Clinical Research, Medical Mycology Research Center kn-affil= affil-num=10 en-affil=Division of Clinical Research, Medical Mycology Research Center kn-affil= affil-num=11 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Brain abscess kn-keyword=Brain abscess en-keyword=Cladophialophora bantiana kn-keyword=Cladophialophora bantiana en-keyword=Black fungus kn-keyword=Black fungus en-keyword=Phaeohyphomycosis kn-keyword=Phaeohyphomycosis en-keyword=Posaconazole kn-keyword=Posaconazole END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=16 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251229 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=FluoNeRF: Fluorescent Novel-View Synthesis Under Novel Light Source Colors and Spectra en-subtitle= kn-subtitle= en-abstract= kn-abstract=Synthesizing photo-realistic images of a scene from arbitrary viewpoints and under arbitrary lighting environments is one of the important research topics in computer vision and graphics. In this paper, we propose a method for synthesizing photo-realistic images of a scene with fluorescent objects from novel viewpoints and under novel lighting colors and spectra. In general, fluorescent materials absorb light with certain wavelengths and then emit light with longer wavelengths than the absorbed ones, in contrast to reflective materials, which preserve wavelengths of light. Therefore, we cannot reproduce the colors of fluorescent objects under arbitrary lighting colors by combining conventional view synthesis techniques with the white balance adjustment of the RGB channels. Accordingly, we extend the novel-view synthesis based on the neural radiance fields by incorporating the superposition principle of light; our proposed method captures a sparse set of images of a scene from varying viewpoints and under varying lighting colors or spectra with active lighting systems such as a color display or a multi-spectral light stage and then synthesizes photo-realistic images of the scene without explicitly modeling its geometric and photometric models. We conducted a number of experiments using real images captured with an LCD and confirmed that our method works better than the existing methods. Moreover, we showed that the extension of our method using more than three primary colors with a light stage enables us to reproduce the colors of fluorescent objects under common light sources. en-copyright= kn-copyright= en-aut-name=ShiLin en-aut-sei=Shi en-aut-mei=Lin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsufujiKengo en-aut-sei=Matsufuji en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaMichitaka en-aut-sei=Yoshida en-aut-mei=Michitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaharaRyo en-aut-sei=Kawahara en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkabeTakahiro en-aut-sei=Okabe en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Artificial Intelligence, Kyushu Institute of Technology kn-affil= affil-num=2 en-affil=Department of Artificial Intelligence, Kyushu Institute of Technology kn-affil= affil-num=3 en-affil=Department of Computer Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Informatics, Kyoto University kn-affil= affil-num=5 en-affil=Department of Computer Science, Okayama University kn-affil= en-keyword=novel-view synthesis kn-keyword=novel-view synthesis en-keyword=neural radiance fields kn-keyword=neural radiance fields en-keyword=relighting kn-keyword=relighting en-keyword=superposition principle kn-keyword=superposition principle en-keyword=fluorescence kn-keyword=fluorescence en-keyword=Stokes shift kn-keyword=Stokes shift END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=e70066 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=A Procedural Transhiatal Approach for the Thoracic Para]Aortic Lymph Node: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=The thoracic posterior para-aortic lymph node (TPAN) is classified as an extra-regional lymph node in esophageal cancer, with metastasis indicating poor prognosis. However, some cases with suspected TPAN metastasis may benefit from esophagectomy with lymph node dissection, including TPAN. This report presents the case of a 58-year-old man with upper thoracic esophageal squamous cell carcinoma and suspected simultaneous TPAN metastasis who underwent neoadjuvant chemotherapy followed by thoracoscopic subtotal esophagectomy and procedural transhiatal TPAN dissection. This transhiatal approach provided direct access to the lymph node without additional thoracic incisions, ensuring safe resection in coordination with the assistant and following anatomical landmarks systematically. Pathological examination showed a false-positive TPAN finding, though the patient later developed distant recurrence. Compared with conventional approaches, this transhiatal technique allows for procedural and reproducible lymphadenectomy while minimizing respiratory burden. This case highlights the feasibility of a transhiatal approach for TPAN dissection. 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=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoHijiri en-aut-sei=Matsumoto en-aut-mei=Hijiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=112aoP kn-keyword=112aoP en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=thoracic posterior para-aortic lymph node kn-keyword=thoracic posterior para-aortic lymph node END start-ver=1.4 cd-journal=joma no-vol=82 cd-vols= no-issue=2 article-no= start-page=E82 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=Crystal structure of tris[4-(3,4-dimethoxythiophen-2-yl)phenyl]amine en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the title compound tris?[4-(3,4-di?meth?oxy?thio?phen-2-yl)phen?yl]amine (DMOT-TPA), C36H33NO6S3, the central nitro?gen atom shows no pyramidalization, with the three para-phenyl?ene rings arranged in a propeller-like geometry. Each thio?phene ring is twisted by about 25?29‹ relative to the adjacent phenyl?ene ring, giving a distorted ƒÎ-conjugated framework. In the crystal, mol?ecules are linked through multiple C?H?ƒÎ inter?actions into two-dimensional sheets, which extend into a three-dimensional network. A Cambridge Structural Database survey revealed no prior examples of tri?phenyl?amines bearing 3,4-di?meth?oxy?thio?phen units at the para positions. This unique structure provides new insights into the design of redox-active organic materials. en-copyright= kn-copyright= en-aut-name=YanoMasafumi en-aut-sei=Yano en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KashiwagiYukiyasu en-aut-sei=Kashiwagi en-aut-mei=Yukiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OishiKoki en-aut-sei=Oishi en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YanoMinori en-aut-sei=Yano en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsudoKoichi en-aut-sei=Mitsudo en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Kansai University kn-affil= affil-num=2 en-affil=Osaka Research Institute of Industrial Science and Technology kn-affil= affil-num=3 en-affil=Kansai University kn-affil= affil-num=4 en-affil=Kansai University kn-affil= affil-num=5 en-affil=Okayama University kn-affil= en-keyword=crystal structure kn-keyword=crystal structure en-keyword=infrared absorption dye kn-keyword=infrared absorption dye en-keyword=one-electron oxidation kn-keyword=one-electron oxidation END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=4 article-no= start-page=74 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Integrated QGIS-Based Evacuation Route Optimization Approach for Disaster Preparedness Against Urban Flood in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Urban inland flooding has become a serious problem in many cities because heavy rain often exceeds the capacity of drainage systems. In Japan, GIS-based evacuation maps are commonly used to support disaster preparedness, but they still have several limitations. In particular, they do not avoid flooded road segments and cannot generate multiple evacuation options at the same time. This study proposes an improved evacuation route method using the free and open-source software QGIS. The method combines flood-depth data with road network processing to remove roads where the predicted water depth is higher than 0.5 m. It also provides several evacuation paths to different shelters at the same time. A case study in Kurashiki City, Okayama Prefecture, demonstrates that about 1.37% of the road network becomes unusable during an inland-flood scenario. Several existing evacuation routes also pass through hazardous areas, but the QGIS-based method avoids these areas in most cases. Since the workflow uses only built-in QGIS functions and does not require programming or plug-ins, it is easy to reproduce and apply in other regions. This study offers a practical and low-cost method to support inland-flood evacuation planning for local governments. en-copyright= kn-copyright= en-aut-name=PanWenliang en-aut-sei=Pan en-aut-mei=Wenliang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PanShijun en-aut-sei=Pan en-aut-mei=Shijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanetoJunko en-aut-sei=Kaneto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaKeisuke en-aut-sei=Yoshida en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiyamaSatoshi en-aut-sei=Nishiyama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=evacuation route kn-keyword=evacuation route en-keyword=hazard mapping kn-keyword=hazard mapping en-keyword=inland flood kn-keyword=inland flood en-keyword=land use analysis kn-keyword=land use analysis en-keyword=QGIS kn-keyword=QGIS END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=6 article-no= start-page=660 end-page=671 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250914 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electronic Structure of the S1 State Manganese Cluster in Photosystem II Investigated Using Q-Band Selective Hole-Burning en-subtitle= kn-subtitle= en-abstract= kn-abstract=The electronic structure of the S1 state of photosystem II (PSII) was investigated using selective hole burning of Q-band pulsed electron paramagnetic resonance. The free induction decay and spin?echo signals of the tyrosine radical YD? in the plant PSII oscillated because of the magnetic dipole?dipole interaction with the S1 state Mn cluster. The initial period was 410 ns (2.44 MHz) and was assigned to the S = 1 spin state. Based on the oscillation analysis, both Mn1 and Mn4 and both Mn2 and Mn3 were assigned as Mn(III) and Mn(IV), respectively, which is consistent with the quantum chemical calculations. The 410 ns period was accounted for in the simplified model using the isotropic spin density distribution ratio [1.6:?1.1:?1.1:1.6] for Mn1?4 ions. This oscillation was identical with that observed in the presence of methanol. The oscillation decreased in PsbP/Q- and PsbO/P/Q-depleted PSII. In Thermosynechococcus vulcanus, two periods, 390 ns (2.56 MHz) and 630 ns (1.59 MHz), were detected, indicating that the cyanobacterial S1 state includes two isomers, S = 1 and S ? 2 spins. The S ? 2 spin was not detected in PsbO/U/V-depleted PSII without polyethylene glycol. The S ? 2 state was consistent with the reported quantum chemical calculation using S = 3. A simplified model accounted for the S = 1 state as the spin density distribution [1.8:?1.3:?1.3:1.8] and for the S ? 2 state as the isotropic spin density distribution [?0.5:0.5:0.5:0.5] for Mn1?4 ions. In combination with quantum chemical calculations, the most probable protonated structure is W1 = H2O, W2 = H2O, O4 = O2?, and O5 = O2? for the S1 state. These results demonstrate that the selective hole burning method is a powerful tool to complement X-ray studies to determine the valence and protonation structure of manganese clusters, not only in the S1 state but also in higher S-states and general metal clusters, which would provide important insights into the water oxidation mechanism. en-copyright= kn-copyright= en-aut-name=KosakiShinya en-aut-sei=Kosaki en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraNaohiko en-aut-sei=Nakamura en-aut-mei=Naohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MinoHiroyuki en-aut-sei=Mino en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Physics, Graduate School of Science, Nagoya University kn-affil= affil-num=2 en-affil=Department of Physics, Graduate School of Science, Nagoya University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Physics, Graduate School of Science, Nagoya University kn-affil= en-keyword=Photosystem II kn-keyword=Photosystem II en-keyword=Oxygen evolution kn-keyword=Oxygen evolution en-keyword=S1 state kn-keyword=S1 state en-keyword=Mn cluster kn-keyword=Mn cluster en-keyword=EPR kn-keyword=EPR en-keyword=Selective hole-burning kn-keyword=Selective hole-burning END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=5 article-no= start-page=101 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prolonged exposure to axitinib alters the molecular profile of Caki?2 renal cell carcinoma cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Axitinib, an oral second?generation multitargeted tyrosine kinase inhibitor, is used as a second?line treatment for metastatic renal cell carcinoma (RCC). However, patients often develop resistance after initial responsiveness, necessitating the elucidation of the underlying resistance mechanisms. Therefore, the present study aimed to investigate the mechanisms underlying axitinib resistance using the Caki?2 human papillary RCC model cells. Cells tolerating 0.1 ?M axitinib were designated as Caki/AX cells. Cell viability was assessed using the water?soluble tetrazolium salt assay. Notably, the 50% inhibitory concentration (IC50) values of axitinib and sunitinib were significantly higher in Caki/AX cells than those in Caki?2 cells, indicating 2.83? and 1.2?fold resistance, respectively. By contrast, the IC50 values of sorafenib and erlotinib were decreased in Caki/AX cells. Moreover, Caki/AX cells showed resistance to everolimus, temsirolimus and rapamycin, and decreased sensitivity to vinblastine, vincristine, paclitaxel, doxorubicin and SN?38 compared with Caki?2 cells. Notably, etoposide, 5?fluorouracil, cisplatin and carboplatin sensitivities were comparable in both cell types. Reverse transcription?quantitative polymerase chain reaction (PCR) analysis revealed that the mRNA levels of the ATP?binding cassette subfamily B member 1 and subfamily G member 2 were significantly higher in Caki/AX cells than those in Caki?2 cells. A PCR array related to vascular endothelial growth factor signalling showed that the mRNA levels of FIGF (also known as vascular endothelial growth factor D) and sphingosine kinase 1 were upregulated, whereas those of Rac family small GTPase 2 were downregulated in Caki/AX cells. Overall, these findings suggested that the upregulation of the ATP?binding cassette subfamily B member 1, FIGF and sphingosine kinase 1 mRNA levels, and downregulation of the Rac family small GTPase 2 mRNA levels may contribute to acquired resistance in Caki/AX cells. en-copyright= kn-copyright= en-aut-name=NakayamaYuko en-aut-sei=Nakayama en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoAya en-aut-sei=Ino en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakaraKohji en-aut-sei=Takara en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University kn-affil= affil-num=2 en-affil=Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University kn-affil= affil-num=3 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University kn-affil= en-keyword=axitinib kn-keyword=axitinib en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma en-keyword=drug resistance kn-keyword=drug resistance en-keyword=ABC transporter kn-keyword=ABC transporter 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=20251229 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genotype?Phenotype Correlations of Li?Fraumeni Syndrome in Japan Children's Cancer Group LFS20 Study Cohort en-subtitle= kn-subtitle= en-abstract= kn-abstract=Li?Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline pathogenic variants in the TP53 gene. With the increasing use of multi-gene panel testing, TP53 variants have been identified in individuals who do not meet established TP53 testing criteria, such as the Chompret criteria. The term gattenuated LFSh has been proposed for some of these cases, particularly those with adult-onset cancer. We analyzed participants of the Japanese nationwide prospective clinical trial of the cancer surveillance program (Japan Children's Cancer Group LFS-20), along with clinical information including their family histories, to better understand their genotypic and phenotypic characteristics. We identified 32 distinct TP53 variants from 41 families (45 participants), including four missense variants with conflicting classifications of pathogenicity in ClinVar. Among these families, 36 (88%) met the LFS criteria (hereafter referred to as gLFSh in contrast to attenuated LFS), while 5 (12%) were classified as attenuated LFS. Including 30 additional family members carrying the same variant, we analyzed 75 individuals with TP53 variants. Of these, 40 with LFS and 6 with attenuated LFS had cancer. Multiple primary cancers occurred in 22 individuals (21 LFS, 1 attenuated LFS). LFS-core tumors accounted for 66% (58/88) of cancers in the LFS group and 63% (5/8) in the attenuated LFS group; of note, all core tumors in the attenuated group were limited to breast cancer. Hotspot missense variants were detected in 11 of 36 LFS families and in none of 5 attenuated LFS families, and non-hotspot null variants were found in 14 and 1, respectively. Our study revealed genotype?phenotype correlations in several respects. UMIN-CTR: UMIN000045855. en-copyright= kn-copyright= en-aut-name=YamazakiFumito en-aut-sei=Yamazaki en-aut-mei=Fumito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakanoYoshiko en-aut-sei=Nakano en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SanadaMasashi en-aut-sei=Sanada en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurahashiHiroki en-aut-sei=Kurahashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyaiShunsuke en-aut-sei=Miyai en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UekiArisa en-aut-sei=Ueki en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeYuko en-aut-sei=Watanabe en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HasegawaDaisuke en-aut-sei=Hasegawa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KarakawaShuhei en-aut-sei=Karakawa en-aut-mei=Shuhei 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=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=InoueEisuke en-aut-sei=Inoue en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatoMotohiro en-aut-sei=Kato en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HattoriHiroyoshi en-aut-sei=Hattori en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Pediatrics, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Genetic Medicine and Services, National Cancer Center Hospital kn-affil= affil-num=3 en-affil=Department of Advanced Diagnosis, Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=4 en-affil=Division of Molecular Genetics, Center for Medical Science, Fujita Health University kn-affil= affil-num=5 en-affil=Division of Molecular Genetics, Center for Medical Science, Fujita Health University kn-affil= affil-num=6 en-affil=Department of Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=7 en-affil=Department of Pediatric Oncology, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, St. Luke's International Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, Hiroshima University Hospital kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Clinical Research Center, NHO Nagoya Medical Center kn-affil= affil-num=13 en-affil=Showa Medical University Research Administration Center, Showa Medical University kn-affil= affil-num=14 en-affil=Department of Pediatrics, The University of Tokyo kn-affil= affil-num=15 en-affil=Department of Clinical Genetics, NHO Nagoya Medical Center kn-affil= en-keyword=cancer predisposition kn-keyword=cancer predisposition en-keyword=genotype?phenotype correlations kn-keyword=genotype?phenotype correlations en-keyword=hotspot variants kn-keyword=hotspot variants en-keyword=Li?Fraumeni syndrome kn-keyword=Li?Fraumeni syndrome en-keyword=TP53 kn-keyword=TP53 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=20251211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Atezolizumab + Chemotherapy for Advanced Non-Small Cell Lung Cancer in Japanese Clinical Practice (J-TAIL-2) en-subtitle= kn-subtitle= en-abstract= kn-abstract=First-line atezolizumab combination therapies were approved for the treatment of metastatic non-small cell lung cancer (NSCLC) based on results from the global phase 3 trials IMpower130, IMpower132, and IMpower150. These trials reported 12-month overall survival (OS) rates of 60%?67% with atezolizumab combination therapy. J-TAIL-2 (NCT04501497), a prospective, multicenter, observational study, evaluated atezolizumab combination therapy in routine clinical practice in Japan. Patients ??20?years old with NSCLC received atezolizumab plus carboplatin and nab-paclitaxel (atezo + CnP), atezolizumab plus carboplatin or cisplatin plus pemetrexed (atezo + PP), or atezolizumab plus bevacizumab plus carboplatin and paclitaxel (atezo + bev?+?CP) in clinical practice. The primary endpoint was the 12-month OS rate. Secondary endpoints included OS, progression-free survival, and subgroup analyses, including IMpower-unlike (did not meet the main eligibility criteria of each IMpower trial) and IMpower-like patients. In total, 814 patients were enrolled (atezo + CnP, n?=?217; atezo + PP, n?=?211; atezo + bev?+?CP, n?=?386). The IMpower-unlike group included patients with Eastern Cooperative Oncology Group performance status ??2, autoimmune disease, or interstitial lung disease. Twelve-month OS rates (95% confidence interval [CI]) were 62.9% (55.8?69.2), 72.1% (65.2?77.9), and 68.3% (63.2?72.9) with atezo + CnP, atezo + PP, and atezo + bev?+?CP, respectively. OS hazard ratios (95% CI) in the IMpower-unlike vs. -like subgroups were 1.36 (0.91?2.05), 1.08 (0.70?1.68), and 1.49 (1.09?2.06), respectively. No new safety signals were observed. Real-world efficacy and safety for each atezolizumab combination were comparable to those in the relevant IMpower trials. en-copyright= kn-copyright= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishioMakoto en-aut-sei=Nishio en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=OsoegawaAtsushi en-aut-sei=Osoegawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiEiki en-aut-sei=Kikuchi en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimuraHideharu en-aut-sei=Kimura en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuJunichi en-aut-sei=Shimizu en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyauchiEisaku en-aut-sei=Miyauchi en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshinoIchiro en-aut-sei=Yoshino en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MisumiToshihiro en-aut-sei=Misumi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeYasutaka en-aut-sei=Watanabe en-aut-mei=Yasutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HataAkito en-aut-sei=Hata en-aut-mei=Akito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KisoharaAkira en-aut-sei=Kisohara en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamaguchiMasafumi en-aut-sei=Yamaguchi en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MiwaAsako en-aut-sei=Miwa en-aut-mei=Asako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IwasawaShunichiro en-aut-sei=Iwasawa en-aut-mei=Shunichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TanakaMisa en-aut-sei=Tanaka en-aut-mei=Misa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GemmaAkihiko en-aut-sei=Gemma en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, Kansai Medical University kn-affil= affil-num=2 en-affil=Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=10 en-affil=International University of Health and Welfare, Narita Hospital kn-affil= affil-num=11 en-affil=Department of Data Science, National Cancer Center Hospital East kn-affil= affil-num=12 en-affil=Department of Thoracic Oncology, Saitama Cancer Center kn-affil= affil-num=13 en-affil=Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Kasukabe Medical Center kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=16 en-affil=Department of Thoracic Oncology, NHO Kyushu Cancer Center kn-affil= affil-num=17 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=18 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=19 en-affil=Chugai Pharmaceutical Co., Ltd. kn-affil= affil-num=20 en-affil=Nippon Medical School kn-affil= en-keyword=atezolizumab kn-keyword=atezolizumab en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=lung cancer kn-keyword=lung cancer en-keyword=non-small cell kn-keyword=non-small cell en-keyword=observational kn-keyword=observational END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=4 article-no= start-page=1041 end-page=1054 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Asian Subgroup Analysis of Patients in the Phase 2 DeLLphi-301 Study of Tarlatamab for Previously Treated Small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Tarlatamab is a bispecific T-cell engager (BiTE?) immunotherapy that binds delta-like ligand 3 on the surface of small cell lung cancer (SCLC) cells and CD3 on T cells, facilitating T cell-mediated cancer cell lysis. In the primary analysis of the phase 2 DeLLphi-301 study (NCT05060016), tarlatamab showed a favourable benefit-to-risk profile with durable objective responses and promising survival outcomes in patients with previously treated SCLC. Here, phase 2 data for the Asia region subgroup are presented.
Methods: Patients with previously treated, advanced SCLC received 10 mg tarlatamab every 2 weeks. The primary endpoint was objective response rate (ORR) by blinded independent central review (RECIST version 1.1). Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. The present analysis includes patients enrolled at sites in Asia.
Results: A total of 43 patients were enrolled at sites in Asia. ORR was 46.3% (95% confidence interval [CI], 30.7?62.6) and median DOR was 7.2 months (95% CI 3.9 to not estimable). The median follow-up was 16.6 months for PFS and 21.2 months for OS. Median PFS was 5.4 months (95% CI 3.0?8.1) and median OS was 19.0 months (95% CI 11.4 to not estimable). The most common treatment-emergent adverse event (AE) was cytokine release syndrome (48.8%), and all such events were grade 1 or 2. There were no discontinuations due to treatment-related AEs.
Conclusions: Tarlatamab demonstrated durable responses and promising survival outcomes with a manageable safety profile in this post hoc analysis of patients from Asia with previously treated SCLC.
Trial Registration: ClinicalTrials.gov, NCT05060016. en-copyright= kn-copyright= en-aut-name=AhnMyung-Ju en-aut-sei=Ahn en-aut-mei=Myung-Ju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChoByoung Chul en-aut-sei=Cho en-aut-mei=Byoung Chul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IzumiHiroki en-aut-sei=Izumi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LeeJong-Seok en-aut-sei=Lee en-aut-mei=Jong-Seok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HanJi-Youn en-aut-sei=Han en-aut-mei=Ji-Youn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ChiangChi-Lu en-aut-sei=Chiang en-aut-mei=Chi-Lu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HuangShuang en-aut-sei=Huang en-aut-mei=Shuang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HamidiAli en-aut-sei=Hamidi en-aut-mei=Ali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MukherjeeSujoy en-aut-sei=Mukherjee en-aut-mei=Sujoy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=XuKrista Lin en-aut-sei=Xu en-aut-mei=Krista Lin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AkamatsuHiraoki en-aut-sei=Akamatsu en-aut-mei=Hiraoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Hematology-Oncology Department, Samsung Medical Center (SMC), Sungkyunkwan University School of Medicine kn-affil= affil-num=2 en-affil=Medical Oncology Department-501, ABMRC, Yonsei University kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Thoracic Oncology, National Cancer Center Hospital East kn-affil= affil-num=5 en-affil=Hematology/Oncology, Seoul National University Bundang Hospital kn-affil= affil-num=6 en-affil=Center for Lung Cancer, National Cancer Center-Graduate School of Cancer Science and Policy kn-affil= affil-num=7 en-affil=Department of Chest Medicine, Taipei Veterans General Hospital kn-affil= affil-num=8 en-affil=Amgen Inc. kn-affil= affil-num=9 en-affil=Amgen Inc. kn-affil= affil-num=10 en-affil=Amgen Inc. kn-affil= affil-num=11 en-affil=Amgen Asia Pacific Pte. Ltd. kn-affil= affil-num=12 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= en-keyword=Small cell lung cancer (SCLC) kn-keyword=Small cell lung cancer (SCLC) en-keyword=Tarlatamab kn-keyword=Tarlatamab en-keyword=DLL3 kn-keyword=DLL3 en-keyword=Bispecific T-cell engager kn-keyword=Bispecific T-cell engager en-keyword=Asian patients kn-keyword=Asian patients END start-ver=1.4 cd-journal=joma no-vol=193 cd-vols= no-issue= article-no= start-page=118724 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Deciphering the structural impact of norepinephrine analog radiopharmaceuticals on organic cation transporter affinity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: Previous studies have investigated the kinetics and affinities of norepinephrine transporter (NET)-targeting radiotracers, including [123I]MIBG, but the role of organic cation transporters (OCTs) remains unclear. This study aimed to evaluate how the structural design of selective NET-targeting tracers affects OCT-mediated non-specific uptake, identifying factors influencing both NET and OCT affinity.
Methods: Cellular uptake assays were conducted using SK-N-SH cells expressing human NET, and human OCT1-, OCT2-, and OCT3-expressing cells with [3H]norepinephrine, [3H]MPP+, and [131I]MIBG. Competitive uptake assays used non-radioactive reference compounds for several NET-targeting radiopharmaceuticals (MIBG, HED, EPI, PHEN, LMI1195, and PHPG), along with a new PET radiotracer [18F]AF78, and its two analogs with meta-iodide [18F]AF78(I) or hydroxyl group [18F]AF78(OH). Dynamic PET imaging in non-human primates assessed the in vivo uptake of [18F]AF78 after NET inhibition with desipramine.
Results: Monoamine-based tracers (EPI, PHEN, HED) exhibited high NET selectivity with minimal OCTs interaction, while guanidine-containing tracers (e.g., MIBG, LMI1195) displayed substantial OCTs affinity. Lower lipophilicity in guanidine-containing compounds, influenced by substitutions on the benzene ring (e.g., PHPG, AF78), correlated with weaker OCT interactions. PET imaging confirmed that cardiac uptake of [18F]AF78 is sensitive to desipramine pretreatment (***P? Conclusion: This study highlights the critical influence of the compoundsf chemical structure on NET and OCT affinities. Structural modifications that reduce OCT-mediated uptake while maintaining high NET affinity could improve the specificity and theranostic potential of NET-targeting ligands. These findings provide insights for designing next-generation radiotracers with enhanced selectivity and clinical utility. en-copyright= kn-copyright= en-aut-name=M?hligSaskia en-aut-sei=M?hlig en-aut-mei=Saskia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenXinyu en-aut-sei=Chen en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TutovAnna en-aut-sei=Tutov en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NoseNaoko en-aut-sei=Nose en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LapaConstantin en-aut-sei=Lapa en-aut-mei=Constantin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WernerRudolf A. en-aut-sei=Werner en-aut-mei=Rudolf A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DeckerMichael en-aut-sei=Decker en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital W?rzburg kn-affil= affil-num=2 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=3 en-affil=Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of W?rzburg kn-affil= affil-num=4 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=6 en-affil=Department of Nuclear Medicine, LMU Hospital, Ludwig-Maximilians-University of Munich kn-affil= affil-num=7 en-affil=Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of W?rzburg kn-affil= affil-num=8 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Norepinephrine transporter kn-keyword=Norepinephrine transporter en-keyword=Organic cation transporter kn-keyword=Organic cation transporter en-keyword=Neuroendocrine tumor kn-keyword=Neuroendocrine tumor en-keyword=Competitive cell uptake kn-keyword=Competitive cell uptake en-keyword=PET radiotracer kn-keyword=PET radiotracer END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=6 article-no= start-page=00362-2025 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Global trends in idiopathic pulmonary fibrosis mortality rates during 2001?2022 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and ultimately fatal lung disease. Updated global mortality data, especially from underexplored countries, are limited. This study aimed to understand the current global trends in IPF-associated mortality rates.
Methods This observational study used the World Health Organization Mortality Database to analyse data stratified by sex, age and geographic region, encompassing 64 countries between 2001 and 2022. IPF was defined according to the International Code for Diseases-10 code J84.1. Crude and age-standardised mortality rates per 100?000 individuals were calculated to estimate long-term mortality trends. Mortality rates were calculated by dividing IPF-associated deaths by the corresponding population, with age-specific rates determined for each 5-year age group. Trends in the 2001?2022 period were analysed using a locally weighted regression model, and the average annual percentage change in mortality rates between 2010 and 2022 was estimated using joinpoint regression analysis.
Results Overall, 874?998 deaths associated with IPF were analysed. The LOESS-smoothed crude mortality rate increased from 2.10 (95% confidence interval (CI) 1.77?2.43) per 100?000 in 2001 to 3.14 (95% CI 2.71?3.57) per 100?000 by 2022. The LOESS-smoothed age-standardised mortality rates increased overall, peaking at 1.59 (95% CI 1.51?1.67) per 100?000 in 2018 and declining slightly to 1.57 (95% CI 1.35?1.79) per 100?000 in 2022. Mortality was higher among males than females; furthermore, 87.5% of deaths occurred in individuals aged ?65?years. Mortality rates were highest among the American population, with a notable increase in Latin American countries.
Conclusion IPF-associated mortality rates have increased globally, particularly in males. Significant geographical, age and sex disparities were observed, emphasising the need for targeted public health measures and improved disease management. en-copyright= kn-copyright= en-aut-name=HaradaKo en-aut-sei=Harada en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=VuQuynh Thi en-aut-sei=Vu en-aut-mei=Quynh Thi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoMaki en-aut-sei=Yamamoto en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=2 en-affil=Division of Hematology/Oncology, Mayo Clinic kn-affil= affil-num=3 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue= article-no= start-page=100718 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Should Japanese athletes undergo booster vaccination for pertussis? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pertussis, a highly contagious respiratory infection caused by Bordetella pertussis, has demonstrated a global resurgence in the post?COVID-19 era, with the emergence of macrolide-resistant strains. In Japan, the routine immunization schedule for pertussis remains limited compared with international standards, leaving young populations under-immunized and at elevated risk of infection. Despite international recommendations for booster vaccinations during adolescence, Japan currently provides only a four-dose primary series during infancy, without subsequent boosters. This immunization gap possibly increases the vulnerability of Japanese athletes to pertussis. Persistent cough can significantly impair athletic performance for weeks to months, posing substantial challenges to professional sports teams. To protect athletesf health and performance capacity and prevent team-wide outbreaks, it is imperative to consider pertussis booster immunizations in Japan, especially for elite athletes. However, DTaP (diphtheria, tetanus, and acellular pertussis) (TRIBIK?) is the only available vaccine in Japan, which contains higher antigen concentrations than the internationally used Tdap (tetanus, diphtheria, pertussis) vaccines (ADACEL? and BOOSTRIX?): the antigen contents of pertussis toxin, filamentous hemagglutinin, and diphtheria toxin in TRIBIK?, ADACEL?, and BOOSTRIX? are 23.5 ?g/23.5 ?g/?15 ?g, 2.5 ?g/5 ?g/2 ?g, and 8 ?g/8 ?g/2.5 ?g, respectively. These differences result in more severe local adverse effects in vaccinees and would complicate booster strategies in Japan. Aligning Japanfs immunization policies with international practices represents a critical step toward ensuring individual health and public safety in increasingly globalized sports environments. 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= affil-num=1 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= en-keyword=Bordetella pertussis kn-keyword=Bordetella pertussis en-keyword=Vaccination kn-keyword=Vaccination en-keyword=Immunization kn-keyword=Immunization END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=7 article-no= start-page=oyaf201 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pharmacovigilance study for the identification of mogamulizumab-induced immune-related adverse events using a real-world database en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Mogamulizumab is a humanized anti-CCR4 monoclonal antibody used for relapsed/refractory adult T-cell leukemia, cutaneous T-cell lymphoma, and/or S?zary syndrome. Reports of immune-related adverse events (irAEs) in these patients are increasing, and the association between irAEs and mogamulizumab remains to be elucidated. This study aimed to evaluate the association between mogamulizumab and immune-related adverse events (irAEs), as well as to characterize the irAEs associated with mogamulizumab using data from a large-scale spontaneous reporting system.
Methods: We performed an exploratory hypothesis-generating analysis of patients from 1967 to September 2023 using VigiBase, a World Health Organization spontaneous adverse event reporting system database. We performed a disproportionality analysis and determined the reporting odds ratios and information components between the drugs of interest and each irAE.
Results: Mogamulizumab was associated with some irAEs, including myocarditis, severe cutaneous adverse reactions, hepatitis, and myositis. Mogamulizumab exhibited significantly higher reporting rates of these 4 irAEs compared to the anticancer agents other than mogamulizumab. Conversely, the reporting rate of other irAEs, including endocrine autoimmune diseases induced by immune checkpoint inhibitors, was not significant in patients who received mogamulizumab.
Conclusions: Mogamulizumab is associated with irAEs, including myocarditis, severe cutaneous adverse reactions, hepatitis, and myositis. en-copyright= kn-copyright= en-aut-name=MiyataKoji en-aut-sei=Miyata en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Izawa-IshizawaYuki en-aut-sei=Izawa-Ishizawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NiimuraTakahiro en-aut-sei=Niimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiokaToshihiko en-aut-sei=Yoshioka en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HyodoMizusa en-aut-sei=Hyodo en-aut-mei=Mizusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItokazuShuto en-aut-sei=Itokazu en-aut-mei=Shuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyataTatsumi en-aut-sei=Miyata en-aut-mei=Tatsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AizawaFuka en-aut-sei=Aizawa en-aut-mei=Fuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YagiKenta en-aut-sei=Yagi en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawadaKei en-aut-sei=Kawada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GodaMitsuhiro en-aut-sei=Goda en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshizawaKeisuke en-aut-sei=Ishizawa en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=4 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=5 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=6 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=7 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=8 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=9 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=10 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=11 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= affil-num=14 en-affil=Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University kn-affil= en-keyword=irAEs kn-keyword=irAEs en-keyword=mogamulizumab kn-keyword=mogamulizumab en-keyword=VigiBase kn-keyword=VigiBase en-keyword=disproportionality analysis kn-keyword=disproportionality analysis en-keyword=s?zary syndrome kn-keyword=s?zary syndrome END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=2 article-no= start-page=100820 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=2026 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Feasibility and Diagnostic Utility of Mucosal T-Cell Flow Cytometry for Intestinal Graft-Versus-Host Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aims: Timely diagnosis of intestinal complications after hematopoietic stem cell transplantation (HSCT), including graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy, and cytomegalovirus infection, is essential for appropriate management. This study evaluated whether mucosal T-cell profiling from endoscopic biopsies could support the diagnosis of these post-transplant conditions.
Methods: We prospectively analyzed 58 intestinal biopsy specimens from 21 post-HSCT patients. Paired samples were obtained from the stomach and duodenum during upper endoscopy and from the ileum and large intestine during colonoscopy. Lymphocytes were isolated from each specimen and analyzed using flow cytometry. These data were integrated with those of a previously collected cohort (35 patients, 51 samples) for comparative immunophenotypic analysis across histologically defined groups.
Results: Duodenal biopsies yielded more lymphocytes than did gastric biopsies (mean } standard deviation: 532 } 823 vs 233 } 392 cells; P = .070), with comparable yields between the ileum and colon. Among 41 evaluable cases, the CD56+:CD3+ ratio was significantly lower in patients with GVHD (5.5 } 2.2%) than in those with nonspecific or no inflammation (28.4 } 16.3%; P = .006). A cutoff value of <11% provided 85.7% sensitivity and 83.3% specificity for diagnosing GVHD (area under the curve = 0.91).
Conclusion: Mucosal T-cell profiling using endoscopic biopsies is feasible and may aid in the diagnosis of GVHD after HSCT. A decreased CD56+:CD3+ ratio is a promising marker for distinguishing GVHD from other post-transplant intestinal conditions. 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=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HiramatsuMai en-aut-sei=Hiramatsu en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirabataAraki en-aut-sei=Hirabata en-aut-mei=Araki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiTakahide en-aut-sei=Takahashi en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=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 Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, 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=cytomegalovirus infection kn-keyword=cytomegalovirus infection en-keyword=flow cytometry kn-keyword=flow cytometry en-keyword=graft-versus-host disease kn-keyword=graft-versus-host disease en-keyword=hematopoietic stem cell transplantation kn-keyword=hematopoietic stem cell transplantation en-keyword=T lymphocytes kn-keyword=T lymphocytes END start-ver=1.4 cd-journal=joma no-vol=122 cd-vols= no-issue=5 article-no= start-page=733 end-page=743 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic pneumonia syndrome (IPS) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has a poor prognosis. Although IPS is often treated with steroids, the disease can become resistant to or dependent on steroid treatment, and there is no effective cure for patients with refractory or steroid-dependent IPS. This multicenter, open-label, single-arm, phase II clinical trial investigated the efficacy and safety of HLC-001 (allogeneic umbilical cord-derived mesenchymal stromal cells) in patients with progressive steroid-dependent or refractory IPS after HSCT. Seven male patients (all male; mean age: 43.3 years) received HLC-001 and three completed the trial. The survival rate at day 56 (primary endpoint) was 71.4% (5/7 patients; 95% confidence interval: 29.0%?96.3%) and was sustained at day 100, suggesting that HLC-001 was more effective than previously reported treatment. Three of the five patients with ??100 days of follow-up died. Five patients experienced at least one adverse drug reaction, none of which were serious. These findings indicate that HLC-001 was potentially effective and generally well tolerated in Japanese patients with steroid-dependent or refractory IPS after HSCT. Given there is no effective cure for steroid-dependent or refractory IPS, HLC-001 may be a promising treatment option and further clinical evaluation is warranted.
Trial registration: Japan Registry of Clinical Trials identifier: jRCT2063220014. en-copyright= kn-copyright= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KakoShinichi en-aut-sei=Kako en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaidaEmiko en-aut-sei=Sakaida en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=4 en-affil=Department of Hematology, Chiba University Hospital kn-affil= affil-num=5 en-affil=Division of Hematology, Department of Medicine, Jichi Medical University kn-affil= en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Hematopoietic stem cell transplantation kn-keyword=Hematopoietic stem cell transplantation en-keyword=Idiopathic pneumonia syndrome kn-keyword=Idiopathic pneumonia syndrome en-keyword=Overall survival kn-keyword=Overall survival en-keyword=Umbilical cord-derived mesenchymal stromal cells kn-keyword=Umbilical cord-derived mesenchymal stromal cells END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=45 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Magnetic Detection of Cancer Cells Using Tumor-Homing Peptide-Modified Magnetic Nanoparticles en-subtitle= kn-subtitle= en-abstract= kn-abstract=Magnetic nanoparticles (MNPs) provide a platform for target detection because of their magnetic responsiveness to alternating magnetic fields (AMFs). We developed a detection method using MNPs modified with tumor-homing peptides (THPs), PL1 and PL3, which selectively bind to protein components enriched in malignant tissues. THP-MNPs were synthesized using maleimide-PEG-NHS linkers and characterized using transmission electron microscopy. Human glioblastoma cancer U87MG and normal tissue-derived HEK293 cells were incubated with THP-MNPs, and the magnetic signals were measured using a high-temperature superconducting quantum interference device (SQUID) magnetometer under an AMF (1.06 kHz). Dark-field microscopy confirmed the preferential binding of THP-MNPs to U87MG cells. In the absence of cells, THP-MNPs exhibited AMF-dependent signal enhancement, which correlated with particle size reduction due to THP release. This increase was completely suppressed in the presence of U87MG cells, indicating a strong THP-mediated interaction. PL3-MNPs exhibited superior discrimination between malignant and non-malignant cells. These results demonstrate that SQUID-based magnetic measurements using THP-MNPs enable rapid and label-free cancer cell detection. en-copyright= kn-copyright= en-aut-name=ZhouShengli en-aut-sei=Zhou en-aut-mei=Shengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FurutaniYuji en-aut-sei=Furutani en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaKei en-aut-sei=Yamashita en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakoSakuya en-aut-sei=Kako en-aut-mei=Sakuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KiwaToshihiko en-aut-sei=Kiwa en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=magnetic nanoparticle kn-keyword=magnetic nanoparticle en-keyword=tumor-homing peptide kn-keyword=tumor-homing peptide en-keyword=superconducting quantum interference devices kn-keyword=superconducting quantum interference devices END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue= article-no= start-page=100857 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A multi-institutional dummy run on segmentation variability and plan quality of stereotactic body radiotherapy for oligometastatic disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and purpose: Oligometastatic disease represents limited metastatic burden, and local ablative therapies such as stereotactic body radiotherapy (SBRT) may improve survival. However, inter-institutional variability in target segmentation and treatment planning can compromise treatment quality. This study aimed to evaluate the segmentation variability and dose distribution quality of SBRT in oligometastatic settings using a multi-institutional dummy run approach.
Methods and materials: Sixty-nine institutions were provided with two anonymized cases of adrenal and spine metastases to delineate targets and organs at risk (OARs) and create intensity-modulated radiotherapy plans following a protocol. Variability was quantified using the Dice similarity coefficient (DSC), Hausdorff distance, and mean distance to agreement. Plan qualities were assessed using the Paddick conformity index, modified gradient index, and a new three-dimensional conformity?gradient index (3D-CGI). Knowledge-based planning (KBP) was applied to explore potential improvements in OAR sparing.
Results: All submitted plans met protocol dose constraints. However, substantial segmentation variability was observed, particularly for the spine case. Among 136 plans, 79% demonstrated acceptable conformity and dose gradients, with 3D-CGI < 6 correlating with favorable distributions. Mean DSC was 0.93 for the clinical target volume and 0.76 for the cauda equina, which showed the highest variability. KBP reduced OAR doses for the adrenal case but showed limited impact for the spine case.
Conclusions: Although dose constraints were achieved, segmentation variability remained substantial, particularly for the cauda equina in the spine case. These findings emphasize inter-institutional differences and the need for standardization and tools to improve SBRT consistency. en-copyright= kn-copyright= en-aut-name=HirashimaHideaki en-aut-sei=Hirashima en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuoYukinori en-aut-sei=Matsuo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshikuraSatoshi en-aut-sei=Ishikura en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakamuraMitsuhiro en-aut-sei=Nakamura en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishibuchiIkuno en-aut-sei=Nishibuchi en-aut-mei=Ikuno kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawaharaDaisuke en-aut-sei=Kawahara en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimadaYoshihisa en-aut-sei=Shimada en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakaharaYoshiro en-aut-sei=Nakahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishioTeiji en-aut-sei=Nishio en-aut-mei=Teiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShikamaNaoto en-aut-sei=Shikama en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WatanabeShun-ichi en-aut-sei=Watanabe en-aut-mei=Shun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=IshibaToshiyuki en-aut-sei=Ishiba en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HaraFumikata en-aut-sei=Hara en-aut-mei=Fumikata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MizowakiTakashi en-aut-sei=Mizowaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University kn-affil= affil-num=2 en-affil=Department of Radiation Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Radiation Oncology, St. Lukefs International Hospital, St. Lukefs International University kn-affil= affil-num=4 en-affil=Department of Advanced Medical Physics, Graduate School of Medicine, Kyoto University kn-affil= affil-num=5 en-affil=Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University kn-affil= affil-num=7 en-affil=Department of Surgery, Tokyo Medical University kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Kitasato University Hospital kn-affil= affil-num=9 en-affil=Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka kn-affil= affil-num=10 en-affil=Department of Radiation Oncology, Juntendo University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=13 en-affil=Department of Breast Surgery, Institute of Science Tokyo kn-affil= affil-num=14 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=15 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=Oligometastatic disease kn-keyword=Oligometastatic disease en-keyword=Dummy run kn-keyword=Dummy run en-keyword=Segmentation variability kn-keyword=Segmentation variability en-keyword=Dose distribution accuracy kn-keyword=Dose distribution accuracy END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue= article-no= start-page=6009610 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=Small Distance Increment Method for Measuring Complex Permittivity With mmWave Radar en-subtitle= kn-subtitle= en-abstract= kn-abstract=Measuring the complex permittivity of material is essential in many scenarios, such as quality checks in material manufacturing. Generally, measurement methods for characterizing the material are based on the use of a vector network analyzer (VNA), which is large and not easy for on-site measurement, especially in high-frequency range such as millimeter wave (mmWave). In addition, some measurement methods require the destruction of samples, which is not suitable for nondestructive inspection. In this work, a small distance increment (SDI) method is proposed to nondestructively measure the complex permittivity of a material. In SDI, the transmitter and receiver are formed as a monostatic radar, which is facing toward the material under test (MUT). During the measurement, the distance between the radar and the MUT changes with small increments, and the signals are recorded at each position. A mathematical model is formulated to depict the relationship among the complex permittivity, distance increment, and measured signals. By fitting the model, the complex permittivity of MUT is estimated. To implement and evaluate the proposed SDI method, a commercial off-the-shelf (COTS) mmWave radar is utilized, and the measurement system is developed. Then, the evaluation was carried out on the acrylic plate. With the proposed method, the estimated complex permittivity of the acrylic plate shows good agreement with the literature values, demonstrating the efficacy of the SDI method for characterizing the complex permittivity of the material. en-copyright= kn-copyright= en-aut-name=SongHang en-aut-sei=Song en-aut-mei=Hang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimHyun Joon en-aut-sei=Kim en-aut-mei=Hyun Joon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WanMingxia en-aut-sei=Wan en-aut-mei=Mingxia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WeiBo en-aut-sei=Wei en-aut-mei=Bo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikkawaTakamaro en-aut-sei=Kikkawa en-aut-mei=Takamaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakadaJun-Ichi en-aut-sei=Takada en-aut-mei=Jun-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Research Institute for Semiconductor Engineering, Hiroshima University kn-affil= affil-num=2 en-affil=Department of Transdisciplinary Science and Engineering, Institute of Science Tokyo kn-affil= affil-num=3 en-affil=Department of Transdisciplinary Science and Engineering, Institute of Science Tokyo kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Research Institute for Semiconductor Engineering, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Transdisciplinary Science and Engineering, Institute of Science Tokyo kn-affil= en-keyword=Complex permittivity measurement kn-keyword=Complex permittivity measurement en-keyword=material characterization kn-keyword=material characterization en-keyword=millimeter wave (mmWave) radar kn-keyword=millimeter wave (mmWave) radar en-keyword=nondestructive inspection kn-keyword=nondestructive inspection en-keyword=small distance increment (SDI) method kn-keyword=small distance increment (SDI) method END start-ver=1.4 cd-journal=joma no-vol=93 cd-vols= no-issue= article-no= start-page=102631 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=Detection of the nuclear translocation of androgen receptor using quantitative and automatic cell imaging analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Testosterone signaling mediates diseases such as androgenetic alopecia and prostate cancer and is controlled by the activation of the androgen receptor (AR) and nuclear translocation of the ligand-receptor complex. This study established an immortalized dermal papilla cell line that stably expresses the AR labeled with a monomeric green fluorescence marker. The cells expressed the histone H2B protein as visualized using a red fluorescence marker, enabling the Detection of nuclear translocation under live cell conditions using image analysis. The AR was observed to be translocated from the cytoplasm to the nucleus of cells after stimulation with dihydrotestosterone (DHT). The signal intensity of the nuclear/cytoplasm ratio was analyzed using automatic image analysis and a newly developed algorithm. The quantitation method to detect nuclear translocation revealed that the AR nuclear signal plateaued approximately 20?min after DHT exposure. Our developed method has the potential to save human labor by the automatic process of the image. en-copyright= kn-copyright= en-aut-name=BaiLanlan en-aut-sei=Bai en-aut-mei=Lanlan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WuTao en-aut-sei=Wu en-aut-mei=Tao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukasawaMizuki en-aut-sei=Fukasawa en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KashiwagiSayo en-aut-sei=Kashiwagi en-aut-mei=Sayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TateHaruka en-aut-sei=Tate en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzakiTaku en-aut-sei=Ozaki en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuganoEriko en-aut-sei=Sugano en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TomitaHiroshi en-aut-sei=Tomita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiiTsuyoshi en-aut-sei=Ishii en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AkashiTakuya en-aut-sei=Akashi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FukudaTomokazu en-aut-sei=Fukuda en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=2 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=3 en-affil=Neuro-AI Integration Science Laboratory, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Rohto Pharmaceutical Co., Ltd., Basic Research Development Division kn-affil= affil-num=5 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=6 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=7 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=8 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= affil-num=9 en-affil=Rohto Pharmaceutical Co., Ltd., Basic Research Development Division kn-affil= affil-num=10 en-affil=Neuro-AI Integration Science Laboratory, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Science and Engineering, Iwate University kn-affil= en-keyword=Dermal papilla cell kn-keyword=Dermal papilla cell en-keyword=Nuclear translocation kn-keyword=Nuclear translocation en-keyword=Androgen receptor kn-keyword=Androgen receptor en-keyword=Live cell imaging kn-keyword=Live cell imaging en-keyword=Digital image analysis kn-keyword=Digital image analysis en-keyword=Quantitation algorithm kn-keyword=Quantitation algorithm END start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue=1 article-no= start-page=1 end-page=4 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=20260101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural and spectroscopic characterization of keatite (SiO2) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Keatite, a polymorph of silica rare in nature, was synthesized by hydrothermal treatment of silicon and water at 100 MPa and 600 ‹C. The crystal structure of keatite at 24 ‹C was refined by the Rietveld method using synchrotron X-ray diffraction data. The obtained structure is consistent with the results of previous studies in which some constraints were imposed during refinements. The 29Si MAS NMR spectrum of keatite shows two peaks at ?113.9 and ?114.3 ppm, which can be assigned to Si at the Si1 and Si2 sites, respectively. The Raman spectrum of keatite shows a prominent peak at 473 cm?1, which is attributable to the Si?O?Si bending mode of the 5-membered ring. These spectra, reported for the first time, are expected to be valuable for the identification of keatite in synthetic and natural samples. en-copyright= kn-copyright= en-aut-name=KanzakiMasami en-aut-sei=Kanzaki en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=XueXianyu en-aut-sei=Xue en-aut-mei=Xianyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= en-keyword=SiO2 kn-keyword=SiO2 en-keyword=Keatite kn-keyword=Keatite en-keyword=Crystal structure kn-keyword=Crystal structure en-keyword=Raman spectroscopy kn-keyword=Raman spectroscopy en-keyword=NMR spectroscopy kn-keyword=NMR spectroscopy 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=85 cd-vols= no-issue=2 article-no= start-page=3437 end-page=3455 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Spectrum Allocation and Security-Sensitive Task Offloading Algorithm in MEC Using DVS en-subtitle= kn-subtitle= en-abstract= kn-abstract=With the advancements of the next-generation communication networking and Internet of Things (IoT) technologies, a variety of computation-intensive applications (e.g., autonomous driving and face recognition) have emerged. The execution of these IoT applications demands a lot of computing resources. Nevertheless, terminal devices (TDs) usually do not have sufficient computing resources to process these applications. Offloading IoT applications to be processed by mobile edge computing (MEC) servers with more computing resources provides a promising way to address this issue. While a significant number of works have studied task offloading, only a few of them have considered the security issue. This study investigates the problem of spectrum allocation and security-sensitive task offloading in an MEC system. Dynamic voltage scaling (DVS) technology is applied by TDs to reduce energy consumption and computing time. To guarantee data security during task offloading, we use AES cryptographic technique. The studied problem is formulated as an optimization problem and solved by our proposed efficient offloading scheme. The simulation results show that the proposed scheme can reduce system cost while guaranteeing data security. en-copyright= kn-copyright= en-aut-name=LiXianwei en-aut-sei=Li en-aut-mei=Xianwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WeiBo en-aut-sei=Wei en-aut-mei=Bo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YangXiaoying en-aut-sei=Yang en-aut-mei=Xiaoying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TolbaAmr en-aut-sei=Tolba en-aut-mei=Amr kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZengZijian en-aut-sei=Zeng en-aut-mei=Zijian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AlfarrajOsama en-aut-sei=Alfarraj en-aut-mei=Osama kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=School of Computer and Information Engineering, Bengbu University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=School of Information Engineering, Suzhou University kn-affil= affil-num=4 en-affil=Computer Science and Engineering Department, College of Applied Studies, King Saud University kn-affil= affil-num=5 en-affil=Institute of Computer Science and Digital Innovation, UCSI University kn-affil= affil-num=6 en-affil=Computer Science and Engineering Department, College of Applied Studies, King Saud University kn-affil= en-keyword=IoT kn-keyword=IoT en-keyword=DVS kn-keyword=DVS en-keyword=MEC kn-keyword=MEC en-keyword=AES kn-keyword=AES END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=3 article-no= start-page=95 end-page=97 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2024 Incentive Award of the Okayama Medical Association in Cardiovascular and Pulmonary Research (2024 Sunada Prize) kn-title=—ߘa‚U”N“x‰ªŽRˆãŠw‰ïÜ@‹¹•”EzŠÂŒ¤‹†§—ãÜi»“cÜj en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KawanaShinichi en-aut-sei=Kawana en-aut-mei=Shinichi kn-aut-name=ì–¼Lˆê kn-aut-sei=ì–¼ kn-aut-mei=Lˆê aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È ŒÄ‹zŠíE“û‘B“à•ª”åŠO‰ÈŠw END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=3 article-no= start-page=92 end-page=94 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2024 Incentive Award of the Okayama Medical Association in General Medical Science (2024 Yuuki Prize) kn-title=—ߘa‚U”N“x‰ªŽRˆãŠw‰ïÜ@‘‡Œ¤‹†§—ãÜiŒ‹éÜj en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name=“’–{“N–ç kn-aut-sei=“’–{ kn-aut-mei=“N–ç aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È@‹~–½‹~‹}EЊQˆãŠw 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. CaMKKƒ¿/1 is tightly regulated by an autoinhibitory mechanism. CaMKKƒÀ/2 activity is highly Ca2+/CaM-independent (autonomous activity) in vitro and Ca2+/CaM-dependent in cultured cells. Whether these two activity states of CaMKKƒÀ/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 CaMKKƒÀ/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 CaMKKƒÀ/2, which was not affected by Ala mutation of Ser128, Ser132, and Ser136. The two activity forms of CaMKKƒÀ/2 had equivalent Ca2+/CaM-binding ability. The findings demonstrate the presence of autonomous and Ca2+/CaM-dependent forms of CaMKKƒÀ/2 independently in mouse tissues and cultured cells. The transition of these states of CaMKKƒÀ/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=695 cd-vols= no-issue= article-no= start-page=123031 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=Flash vaporization and migration of iodine in the oceanic plate subduction zone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Crustal fluids in subduction zones, such as subsurface aquifers, submarine seeps, and gas hydrate waters, are often rich in iodine (I2) and methane (CH4). Large-scale aquifers in the Kanto subduction zone, where the Pacific Plate (PAC) and the Philippine Sea Plate (PHS) are subducting, also exhibit high concentrations of I2 and CH4. However, the origin and behavior of I2 in the subduction zone are unclear, and its coexistence with CH4 remains unresolved. To investigate this, we compiled the I2 phase diagram under high-pressure and high-temperature (P?T) conditions to predict its physicochemical properties in the subduction zone. We then applied the P?T paths of subducted PAC and PHS sediments to the I2 phase diagram. Our findings reveal that I2 can exist as a liquid in the young and hot PHS subduction zone. Transient decompressions during earthquake ruptures can cause liquid iodine to flash-vaporize and be expelled from subducted sediments. Along with I2, thermogenic CH4 and hydrogen (H2) generated in the subducted sediments are also released and transported upward, likely by slab-dehydrated fluids. Additionally, H2 may enhance microbial CH4 production through hydrogenotrophic methanogenesis. In subduction zones of young and hot oceanic plates such as the PHS, crustal fluids are enriched in I2 and coexist with CH4 owing to the simultaneous expulsion of I2, CH4, and H2 from the same subducted sediments and their migration via deep fluids. Large subsurface aquifers can act as traps and reservoirs for migrating I2 and CH4, forming large-scale I2 and CH4 deposits. en-copyright= kn-copyright= en-aut-name=SuzukiNoriyuki en-aut-sei=Suzuki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KamedaJun en-aut-sei=Kameda en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AmoMiki en-aut-sei=Amo en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Earth and Planetary Sciences, Faculty of Science, Hokkaido University kn-affil= affil-num=2 en-affil=Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=Geology and Geophysics Division, Technology Department, Japan Organization for Metals and Energy Security kn-affil= en-keyword=Iodine circulation kn-keyword=Iodine circulation en-keyword=Flash vaporization kn-keyword=Flash vaporization en-keyword=Microbial methane kn-keyword=Microbial methane en-keyword=Thermogenic methane kn-keyword=Thermogenic methane en-keyword=Thermogenic hydrogen kn-keyword=Thermogenic hydrogen en-keyword=Subducted sediments kn-keyword=Subducted sediments END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=8 article-no= start-page=938 end-page=943 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical outcomes of Japanese patients treated with out-of-specification tisagenlecleucel in a phase 3b trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The final manufactured tisagenlecleucel product should meet the commercial product release specifications to ensure the quality in terms of safety, purity, identity, and potency. However, it may occasionally fail to meet these specifications due to the nature of patient-derived cells with variable properties as starting material and the complex manufacturing process. The final product that does not meet at least one of the commercial release specifications is referred to as gout-of-specificationh (OOS). However, the benefit-risk profile of OOS tisagenlecleucel has not yet been fully elucidated.
Aims: To evaluate the safety and efficacy of OOS tisagenlecleucel in Japanese patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia (B-ALL).
Methods: This is a single-arm, open-label, multicenter phase 3b study (NCT04094311). Patients consistent with label indication were enrolled and followed-up for 3 months.
Results: Of the 29 patients enrolled between December 2019 and May 2022 across 13 qualified sites in Japan, 28 received tisagenlecleucel, and of these, 23 had r/r DLBCL and 5 had r/r B-ALL. The primary reasons for OOS were low cell viability (15 of 24 batches) and low dose (8 of 23 batches) tisagenlecleucel in the r/r DLBCL group, and high dose (4 of 5 batches) in the r/r B-ALL group. In patients with r/r DLBCL, the grade 3 or 4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 3 and 1 patients, respectively. Response assessments were performed for 15 of 23 patients with r/r DLBCL: 6 achieved a complete response, and 1 achieved a partial response as the best response within 3 months.
Conclusions: Despite the limited patient sample size, our findings affirm that the infusion of OOS tisagenlecleucel is a viable option, with no observed increase in toxicity and outcomes comparable to those of in-specification products in clinical and real-world studies. en-copyright= kn-copyright= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoJun en-aut-sei=Kato en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GotoHideki en-aut-sei=Goto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiTakeshi en-aut-sei=Kobayashi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiYoshiyuki en-aut-sei=Takahashi en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakaidaEmiko en-aut-sei=Sakaida en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiramatsuHidefumi en-aut-sei=Hiramatsu en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoMasahide en-aut-sei=Yamamoto en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiharaSatoshi en-aut-sei=Yoshihara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AndoJun en-aut-sei=Ando en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KohKatsuyoshi en-aut-sei=Koh en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FukushimaKentaro en-aut-sei=Fukushima en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IwamotoFumiko en-aut-sei=Iwamoto en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TiwariRanjan en-aut-sei=Tiwari en-aut-mei=Ranjan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University Hospital kn-affil= affil-num=2 en-affil=Division of Hematology, Department of Medicine, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital kn-affil= affil-num=4 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Hematology, Chiba University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatrics, Graduate School of Medicine, Kyoto University kn-affil= affil-num=8 en-affil=Department of Hematology, Institute of Science Tokyo Hospital kn-affil= affil-num=9 en-affil=Department of Hematology, Hyogo Medical University Hospital kn-affil= affil-num=10 en-affil=Department of Cell Therapy and Transfusion Medicine, Juntendo University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Hematology/Oncology, Saitama Childrenfs Medical Center kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Osaka University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Medical Affairs, Novartis Pharma K.K. kn-affil= affil-num=14 en-affil=Development Advance Quantitative Sciences, Novartis Healthcare Private Limited kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=CAR-T kn-keyword=CAR-T en-keyword=DLBCL kn-keyword=DLBCL en-keyword=Out-of-specification kn-keyword=Out-of-specification en-keyword=Safety kn-keyword=Safety en-keyword=Tisagenlecleucel kn-keyword=Tisagenlecleucel END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=11 article-no= start-page=105889 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=Association between adjuvant chemotherapy and outcomes in resected locoregional recurrence of hormone receptor-positive HER2-negative breast cancer: a multi-institutional retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: To evaluate the association of adjuvant chemotherapy and prognosis for locoregional recurrence (LRR) in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative subtype breast cancer.
Patients and methods: We carried out a multi-institutional retrospective cohort study in patients with breast cancer who developed HR-positive HER2-negative LRR. Patients who underwent curative surgery for LRR between 2014 and 2018 were categorized based on whether they received adjuvant chemotherapy for LRR (CTx versus no-CTx). Invasive disease-free survival (iDFS) was evaluated between the groups by Cox proportional hazards analysis. The primary analysis used a double-robust Cox model incorporating inverse probability of treatment weighting, and a sensitivity analysis using propensity score matching was also carried out.
Results: A total of 958 patients were included. The median time from the primary surgery to LRR diagnosis was 9.5 years (interquartile range 3.1-10.1 years). There were 235 patients (25%) in the CTx group and 722 (75%) in the no-CTx group. Among all patients, the 5-year iDFS rate was 75.4% [95% confidence interval (CI) 72.4% to 78.2%]. Multivariate analysis showed better iDFS in the CTx group (hazard ratio 0.70, 95% CI 0.49-0.99, P = 0.045). Sensitivity analysis supported these findings. Subgroup analyses showed that the CTx group had better iDFS in cases with non-ipsilateral breast tumor recurrence (IBTR), recurrences during adjuvant endocrine therapy for primary breast cancer, and without perioperative chemotherapy for primary breast cancer. Secondary analysis showed no significant difference with a worse trend toward overall survival in the CTx group with multivariate Cox proportional hazards analysis.
Conclusion: Adjuvant chemotherapy for HR-positive HER2-negative LRR was associated with better iDFS, particularly in cases of non-IBTR, recurrences during adjuvant endocrine therapy, and no prior perioperative chemotherapy for their primary tumor. However, the retrospective design and inability to distinguish true recurrences from new primary tumors in IBTR warrant cautious interpretation. en-copyright= kn-copyright= en-aut-name=OzakiY. en-aut-sei=Ozaki en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TokudaE. en-aut-sei=Tokuda en-aut-mei=E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SagaraY. en-aut-sei=Sagara en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaraF. en-aut-sei=Hara en-aut-mei=F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasadaS. en-aut-sei=Sasada en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SawakiM. en-aut-sei=Sawaki en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanbayashiC. en-aut-sei=Kanbayashi en-aut-mei=C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamanakaT. en-aut-sei=Yamanaka en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OnishiT. en-aut-sei=Onishi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujikiY. en-aut-sei=Fujiki en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SutoA. en-aut-sei=Suto en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakahashiY. en-aut-sei=Takahashi en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TokunagaE. en-aut-sei=Tokunaga en-aut-mei=E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ArugaT. en-aut-sei=Aruga en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraR. en-aut-sei=Nakamura en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujisawaT. en-aut-sei=Fujisawa en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SajiS. en-aut-sei=Saji en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IwataH. en-aut-sei=Iwata en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShienT. en-aut-sei=Shien en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research kn-affil= affil-num=2 en-affil=Department of Medical Oncology, Fukushima Medical University kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital kn-affil= affil-num=4 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=5 en-affil=Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Breast Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=7 en-affil=Department of Breast Oncology, Niigata Cancer Center Hospital kn-affil= affil-num=8 en-affil=Department of Breast Surgery and Oncology, Kanagawa Cancer Center kn-affil= affil-num=9 en-affil=Department of Breast Oncology, National Cancer Center Hospital East kn-affil= affil-num=10 en-affil=Department of Breast Surgery, Social Medical Corporation Hakuaikai Sagara Hospital kn-affil= affil-num=11 en-affil=Department of Breast Oncology, National Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center kn-affil= affil-num=14 en-affil=Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=15 en-affil=Division of Breast Surgery, Chiba Cancer Center kn-affil= affil-num=16 en-affil=Department of Breast Oncology, Gunma Prefectural Cancer Center kn-affil= affil-num=17 en-affil=Department of Medical Oncology, Fukushima Medical University kn-affil= affil-num=18 en-affil=Department of Advanced Clinical Research and Development, Nagoya City University kn-affil= affil-num=19 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=locoregional recurrence kn-keyword=locoregional recurrence en-keyword=adjuvant chemotherapy kn-keyword=adjuvant chemotherapy en-keyword=inverse probability of treatment weighting kn-keyword=inverse probability of treatment weighting END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=12 article-no= start-page=1811 end-page=1825 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250926 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of Fentanyl-Emerged Adverse Events and Pharmacokinetics in Neonates: A Physiologically Based Pharmacokinetic Modeling Approach en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Despite its common use for analgesia in neonatal intensive care units, the optimal dosing and safety profile of fentanyl, particularly regarding suspected fentanyl-emerged adverse events (FEAEs), such as hypotension, desaturation, and oliguria, are not well-defined.
Objective This study aimed to develop an optimal therapeutic monitoring and dosing strategy for fentanyl for neonates. A physiologically based pharmacokinetic (PBPK) model for predicting fentanyl pharmacokinetics across various populations, including preterm and term neonates, was developed, and the relationship between predicted fentanyl exposure and FEAE incidence in neonates was assessed.
Methods A PBPK model was developed and validated against the observed values in the literature. The modelfs predictive accuracy for fentanyl pharmacokinetics and association with FEAE incidence in an external retrospective cohort of Japanese neonates was evaluated using the predicted concentrations and pharmacokinetic parameters estimated by PBPK simulation.
Results The PBPK model exhibited reasonable predictive performance for serum fentanyl concentrations in actual neonatal patients (mean error: 9.27% [standard error: 5.06%], root mean squared error: 54.7%). The incidence of any FEAE, particularly oxygen desaturation, was associated with the fentanyl concentration-to-dose ratio, but not with some exposure parameters, such as the area under the curve and maximum concentration. The recommended reduced infusion rate allowed serum fentanyl concentrations to fall within the ranges established by the reported values and our data.
Conclusions Our PBPK model and proposed dosing strategy may contribute to safer and more effective fentanyl use in neonates. en-copyright= kn-copyright= en-aut-name=MahdyWalaa Yousef Bassyouni en-aut-sei=Mahdy en-aut-mei=Walaa Yousef Bassyouni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JojiRisa en-aut-sei=Joji en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoMari en-aut-sei=Hashimoto en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakasoneRuka en-aut-sei=Nakasone en-aut-mei=Ruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiokaKazumichi en-aut-sei=Fujioka en-aut-mei=Kazumichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItoharaKotaro en-aut-sei=Itohara en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YanoIkuko en-aut-sei=Yano en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=2 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=4 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Graduate School of Medicine, Kobe University kn-affil= affil-num=6 en-affil=Department of Pediatrics, Graduate School of Medicine, Kobe University kn-affil= affil-num=7 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=9 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=10 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=1 article-no= start-page=69 end-page=84 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=P53-Armed Oncolytic Virotherapy Promotes the Efficacy of PD1 Blockade in Murine Osteosarcoma Tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Osteosarcoma (OS) is refractory to immune checkpoint inhibitors targeting programmed cell death 1 (PD1)/PD ligand 1 (PD-L1) due to poor immune response. We previously developed telomerase-specific, replication-competent oncolytic adenoviruses non-armed OBP-301 and P53-armed OBP-702 that exert antitumor efficacy against human OS cells. Recently, we demonstrated that P53-armed OBP-702 induces more profound immunogenic cell death and antitumor immune response against human and murine OS cells than does non-armed OBP-301. In the present study, we assessed the combined efficacy of PD1 blockade and P53-armed OBP-702 against murine OS cells.
Materials and Methods: Three murine OS cell lines (K7M2, NHOS, NHOS-LM4) were used to assess the cytopathic effect of non-armed OBP-301 and P53-armed OBP-702 by XTT assay. Virus-induced immunogenic cell death was assessed by analyzing the levels of extracellular adenosine triphosphate and high-mobility group box protein B1. The expression of PD-L1 and PD-L2 was analyzed by flow cytometry. The malignant potential of NHOS-LM4 cells was analyzed by a migration and invasion assay. An orthotopic NHOS-LM4 tumor model was used to evaluate the antitumor efficacy of combination therapy with P53-armed OBP-702 and anti-PD1.
Results: P53-armed OBP-702 exhibited antitumor potential for the induction of immunogenic cell death, apoptosis, autophagy, and PD-L1/2 upregulation in K7M2 and NHOS cells. NHOS-LM4 cells showed increased migratory and invasive ability compared to NHOS cells. P53-armed OBP-702 significantly suppressed the malignant potential of NHOS-LM4 cells. Combination dosing showed that P53-armed OBP-702 significantly promoted the antitumor effect of PD1 blockade against NHOS-LM4 tumors.
Conclusion: Our results suggest that P53-armed OBP-702 is a promising agent for improving the antitumor effect of PD1 blockade in treating invasive OS. en-copyright= kn-copyright= en-aut-name=KUREMIHO en-aut-sei=KURE en-aut-mei=MIHO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TAZAWAHIROSHI en-aut-sei=TAZAWA en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DEMIYAKOJI en-aut-sei=DEMIYA en-aut-mei=KOJI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KONDOHIROYA en-aut-sei=KONDO en-aut-mei=HIROYA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MOCHIZUKIYUSUKE en-aut-sei=MOCHIZUKI en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KOMATSUBARATADASHI en-aut-sei=KOMATSUBARA en-aut-mei=TADASHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YOSHIDAAKI en-aut-sei=YOSHIDA en-aut-mei=AKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UOTANIKOJI en-aut-sei=UOTANI en-aut-mei=KOJI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HASEIJOE en-aut-sei=HASEI en-aut-mei=JOE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=KUNISADATOSHIYUKI en-aut-sei=KUNISADA en-aut-mei=TOSHIYUKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=URATAYASUO en-aut-sei=URATA en-aut-mei=YASUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KAGAWASHUNSUKE en-aut-sei=KAGAWA en-aut-mei=SHUNSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OZAKITOSHIFUMI en-aut-sei=OZAKI en-aut-mei=TOSHIFUMI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Orthopaedic 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 Orthopaedic 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= en-keyword=Osteosarcoma kn-keyword=Osteosarcoma en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=P53 kn-keyword=P53 en-keyword=immunogenic cell death kn-keyword=immunogenic cell death en-keyword=PD1 kn-keyword=PD1 END start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=1 article-no= start-page=25 end-page=38 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Near-infrared Photoimmunotherapy Targeting High-risk Human Neuroblastoma Cells Expressing GD2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system in infancy. Despite advances in treatment, the prognosis remains poor for high-risk NB patients. Although immunotherapy using anti-GD2 antibodies is available for high-risk NB, the therapeutic efficacy is insufficient. Near-infrared photoimmunotherapy (NIR-PIT) is an antitumor strategy that induces tumor-specific cytotoxicity by combining an antibody-photoabsorber conjugate (APC) with NIR light irradiation. In this study, we investigated the therapeutic efficacy of GD2-targeted NIR-PIT against human NB cells.
Materials and Methods: GD2 expression was analyzed on the surface of high-risk human NB cells (CHP-134, LA-N-5, IMR-32) and non-high-risk human NB cells (SK-N-SH) by flow cytometry. The APC was synthesized by incubating anti-GD2 antibody and IR700. The cytotoxic effect of GD2-targeted NIR-PIT was evaluated using the XTT assay. The distribution of dead cells within tumor spheres was evaluated using a live/dead assay. The in vivo antitumor effect of GD2-targeted NIR-PIT was assessed using a subcutaneous human NB xenograft tumor model.
Results: GD2 protein was expressed on the surface of CHP-134, LA-N-5, and IMR-32 cells but not SK-N-SH cells. GD2-targeted NIR-PIT significantly suppressed the viability of GD2-positive NB cells but not GD2-negative NB cells, compared to the control and monotherapy groups. GD2-targeted NIR-PIT significantly reduced the volume of GD2-positive CHP-134 tumor spheres by inducing the accumulation of dead cells. Subcutaneous CHP-134 xenograft tumor models demonstrated that GD2-targeted NIR-PIT significantly inhibited tumor growth compared with the control and monotherapy groups.
Conclusion: GD2-targeted NIR-PIT is a promising antitumor strategy for treating high-risk NB tumors expressing GD2. en-copyright= kn-copyright= en-aut-name=NOUSOHIROSHI en-aut-sei=NOUSO en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TAZAWAHIROSHI en-aut-sei=TAZAWA en-aut-mei=HIROSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TANIMOTOTERUTAKA en-aut-sei=TANIMOTO en-aut-mei=TERUTAKA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TANIMORIMICHI en-aut-sei=TANI en-aut-mei=MORIMICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WATANABEHINAKO en-aut-sei=WATANABE en-aut-mei=HINAKO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OYAMATAKANORI en-aut-sei=OYAMA en-aut-mei=TAKANORI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NOMAKAZUHIRO en-aut-sei=NOMA en-aut-mei=KAZUHIRO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=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=KOBAYASHIHISATAKA en-aut-sei=KOBAYASHI en-aut-mei=HISATAKA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NODATAKUO en-aut-sei=NODA en-aut-mei=TAKUO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=FUJIWARATOSHIYOSHI en-aut-sei=FUJIWARA en-aut-mei=TOSHIYOSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Pediatric 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 Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pediatric 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=Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health kn-affil= affil-num=10 en-affil=Department of Pediatric 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= en-keyword=Neuroblastoma kn-keyword=Neuroblastoma en-keyword=GD2 kn-keyword=GD2 en-keyword=near-infrared photoimmunotherapy kn-keyword=near-infrared photoimmunotherapy en-keyword=IR700 kn-keyword=IR700 END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page= 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=Adaptive Topological Mapping With Free Area-Based Node Deletion for Autonomous Mobile Robots en-subtitle= kn-subtitle= en-abstract= kn-abstract=This paper proposes an adaptive topological map building method, called Adaptive Resonance Theory-based Topological Clustering with Different Topologies (ATC-DT), for autonomous mobile robots using 3D point cloud data. ATC-DT framework integrates a novel node deletion mechanism that detects layout changes through free area detection. This allows the robot to update topological maps dynamically, removing outdated nodes caused by environmental changes. Experiments in real environments validate the ability of the method to perform global path planning, free area estimation, and adaptive navigation. The approach significantly improves navigation performance by improving map relevance and reducing redundancy of paths. en-copyright= kn-copyright= en-aut-name=OzakiHaruka en-aut-sei=Ozaki en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TodaYuichiro en-aut-sei=Toda en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MasuyamaNaoki en-aut-sei=Masuyama en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiKai en-aut-sei=Fuji en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsunoTakayuki en-aut-sei=Matsuno en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Informatics, Osaka Metropolitan University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Topological map building kn-keyword=Topological map building en-keyword=navigation system kn-keyword=navigation system en-keyword=autonomous mobile robot kn-keyword=autonomous mobile robot END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=RP99936 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250811 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Redistribution of fragmented mitochondria ensures symmetric organelle partitioning and faithful chromosome segregation in mitotic mouse zygotes en-subtitle= kn-subtitle= en-abstract= kn-abstract=In cleavage-stage embryos, preexisting organelles partition evenly into daughter blastomeres without signi?cant cell growth after symmetric cell division. The presence of mitochondrial DNA within mitochondria and its restricted replication during preimplantation development makes their inheritance particularly important. While chromosomes are precisely segregated by the mitotic spindle, the mechanisms controlling mitochondrial partitioning remain poorly understood. In this study, we investigate the mechanism by which Dynamin-related protein 1 (Drp1) controls the mitochondrial redistribution and partitioning during embryonic cleavage. Depletion of Drp1 in mouse zygotes causes marked mitochondrial aggregation, and the majority of embryos arrest at the 2 cell stage. Clumped mitochondria are located in the center of mitotic Drp1-depleted zygotes with less uniform distribution, thereby preventing their symmetric partitioning. Asymmetric mitochondrial inheritance is accompanied by functionally inequivalent blastomeres with biased ATP and endoplasmic reticulum Ca2+ levels. We also find that marked mitochondrial centration in Drp1-depleted zygotes prevents the assembly of parental chromosomes, resulting in chromosome segregation defects and binucleation. Thus, mitochondrial fragmentation mediated by Drp1 ensures proper organelle positioning and partitioning into functional daughters during the first embryonic cleavage. en-copyright= kn-copyright= en-aut-name=GekkoHaruna en-aut-sei=Gekko en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomuraRuri en-aut-sei=Nomura en-aut-mei=Ruri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuzuharaDaiki en-aut-sei=Kuzuhara en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KaneyasuMasato en-aut-sei=Kaneyasu en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KosekiGenpei en-aut-sei=Koseki en-aut-mei=Genpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AdhikariDeepak en-aut-sei=Adhikari en-aut-mei=Deepak kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MioYasuyuki en-aut-sei=Mio en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CarrollJohn en-aut-sei=Carroll en-aut-mei=John kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KonoTomohiro en-aut-sei=Kono en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FunahashiHiroaki en-aut-sei=Funahashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Reproductive Centre, Mio Fertility Clinic kn-affil= affil-num=4 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Development and Stem Cell Program and Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University kn-affil= affil-num=7 en-affil=Reproductive Centre, Mio Fertility Clinic kn-affil= affil-num=8 en-affil=Development and Stem Cell Program and Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University kn-affil= affil-num=9 en-affil=Department of Bioscience, Tokyo University of Agriculture kn-affil= affil-num=10 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=11 en-affil=Department of Animal Science, Graduate School of Environment and Life Science, Okayama University kn-affil= 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=38 cd-vols= no-issue=2 article-no= start-page=222 end-page=225 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ethical Use of Cadaveric Images in Anatomical Textbooks, Atlases, and Journals: A Consensus Response From Authors and Editors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, consent to use donor bodies for medical education and research is obtained from the body donors and their families before the donation. Recently, the International Federation of Associations of Anatomists (IFAA) published guidelines that could restrict the appearance of cadaveric images in commercial anatomical resources such as textbooks and other educational products. These guidelines state that the donor must expressly consent to using such images for this purpose. Cadaveric photos and drawings made from dissections of cadavers have been used in anatomy textbooks and atlases for hundreds of years. They are invaluable for anatomy students and clinical/surgical practitioners. The IFAA guidelines should not restrict the use of those older books; to do so would infringe the rights of those seeking knowledge from these resources. As the images in such textbooks and atlases are anonymized and are used for teaching and research, and the donors and their families are informed about this before the donation, we believe no additional consent is needed. It is impossible to separate educational from gcommercialh usage entirely in any situation, e.g., publications from publishers and the use of cadavers in medical schools. Therefore, our best efforts to avoid unethical use of cadaveric images by following traditional consent processes are still needed so that more people will reap the benefits from them. As senior textbook/atlas authors/editors from over 10 countries, we believe that using cadaveric images in anatomy textbooks is appropriate, and no additional consent should be necessary. Such usage falls within the good faith of professionals using these invaluable gifts. en-copyright= kn-copyright= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimHee]Jin en-aut-sei=Kim en-aut-mei=Hee]Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkitaKeiichi en-aut-sei=Akita en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LoganBari M. en-aut-sei=Logan en-aut-mei=Bari M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HutchingsRalph T. en-aut-sei=Hutchings en-aut-mei=Ralph T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OttoneNicol?s en-aut-sei=Ottone en-aut-mei=Nicol?s kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NonakaYoichi en-aut-sei=Nonaka en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AnandMahindra en-aut-sei=Anand en-aut-mei=Mahindra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BurnsDanny en-aut-sei=Burns en-aut-mei=Danny kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SinghVishram en-aut-sei=Singh en-aut-mei=Vishram kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Peris]CeldaMaria en-aut-sei=Peris]Celda en-aut-mei=Maria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=Martinez]SorianoFrancisco en-aut-sei=Martinez]Soriano en-aut-mei=Francisco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ApaydinNihal en-aut-sei=Apaydin en-aut-mei=Nihal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HannaAmgad en-aut-sei=Hanna en-aut-mei=Amgad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YoshiokaNobutaka en-aut-sei=Yoshioka en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Fernandez]MirandaJuan en-aut-sei=Fernandez]Miranda en-aut-mei=Juan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HurMi]Sun en-aut-sei=Hur en-aut-mei=Mi]Sun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShojaMohammadali M. en-aut-sei=Shoja en-aut-mei=Mohammadali M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SaremiFarhood en-aut-sei=Saremi en-aut-mei=Farhood kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ReinaFrancisco en-aut-sei=Reina en-aut-mei=Francisco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TabiraYoko en-aut-sei=Tabira en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=CarreraAnna en-aut-sei=Carrera en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SprattJonathan D. en-aut-sei=Spratt en-aut-mei=Jonathan D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HoS. Yen en-aut-sei=Ho en-aut-mei=S. Yen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=MoriShumpei en-aut-sei=Mori en-aut-mei=Shumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KomuneNoritaka en-aut-sei=Komune en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=WatanabeKoichi en-aut-sei=Watanabe en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=Prats]GalinoAlberto en-aut-sei=Prats]Galino en-aut-mei=Alberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=De Andr?sJose en-aut-sei=De Andr?s en-aut-mei=Jose kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ReinaMiguel Angel en-aut-sei=Reina en-aut-mei=Miguel Angel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=AbrahamsPeter H. en-aut-sei=Abrahams en-aut-mei=Peter H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=AndersonRobert H. en-aut-sei=Anderson en-aut-mei=Robert H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=LoukasMarios en-aut-sei=Loukas en-aut-mei=Marios kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=TubbsR. Shane en-aut-sei=Tubbs en-aut-mei=R. Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= affil-num=1 en-affil=Department of Neurosurgery, Tulane University School of Medicine kn-affil= affil-num=2 en-affil=Division in Anatomy & Development Biology, Department of Oral Biology, Yonsei University College of Dentistry kn-affil= affil-num=3 en-affil=Department of Clinical Anatomy, Tokyo Medical and Dental University (TMDU) kn-affil= affil-num=4 en-affil=UK kn-affil= affil-num=5 en-affil=UK kn-affil= affil-num=6 en-affil=Department of Integral Adult Dentistry, Center for Research in Dental Sciences (CICO), Dental School, Universidad de La Frontera kn-affil= affil-num=7 en-affil=Department of Neurosurgery, Tokai University School of Medicine kn-affil= affil-num=8 en-affil=Department of Anatomy, Rama Medical College & Research Centre kn-affil= affil-num=9 en-affil=Department of Anatomical Sciences, School of Medicine, St. George's University kn-affil= affil-num=10 en-affil=Department of Anatomy, Kasturba Medical College Mangalore, Manipal Academy of Higher Education kn-affil= affil-num=11 en-affil=Department of Neurologic Surgery, Mayo Clinic kn-affil= affil-num=12 en-affil=Department of Anatomy, University of Valencia kn-affil= affil-num=13 en-affil=Department of Anatomy, Faculty of Medicine, Ankara University kn-affil= affil-num=14 en-affil=Department of Neurological Surgery, University of Wisconsin kn-affil= affil-num=15 en-affil=Department of Neuroplastic and Reconstructive Surgery Social Medical Corporation Kotobukikai Tominaga Hospital kn-affil= affil-num=16 en-affil=Department of Neurosurgery, Stanford University School of Medicine kn-affil= affil-num=17 en-affil=Department of Anatomy, Daegu Catholic University School of Medicine kn-affil= affil-num=18 en-affil=Department of Medical Education, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University (NSU) kn-affil= affil-num=19 en-affil=Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Ronald Reagan UCLA Medical Center kn-affil= affil-num=20 en-affil=Medical Sciences Department, Faculty of Medicine, Clinical Anatomy, Embryology and Neuroscience Research Group, University of Girona kn-affil= affil-num=21 en-affil=Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine kn-affil= affil-num=22 en-affil=Medical Sciences Department, Faculty of Medicine, Clinical Anatomy, Embryology and Neuroscience Research Group, University of Girona kn-affil= affil-num=23 en-affil=University Hospital of North Durham kn-affil= affil-num=24 en-affil=Cardiac Morphology, Royal Brompton & Harefield Hospitals kn-affil= affil-num=25 en-affil=University of California Los Angeles (UCLA) Cardiac Arrhythmia Center, Cardiovascular and Interventional Programs, UCLA Health System, David Geffen School of Medicine at UCLA kn-affil= affil-num=26 en-affil=Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=27 en-affil=Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine kn-affil= affil-num=28 en-affil=Laboratory of Surgical NeuroAnatomy (LSNA), director of the Body Donation and Dissection Rooms Service, Faculty of Medicine and Health of Science, University of Barcelona kn-affil= affil-num=29 en-affil=Surgery Specialties Department, University of Valencia kn-affil= affil-num=30 en-affil=CEU]San]Pablo University School of Medicine kn-affil= affil-num=31 en-affil=Warwick Medical School kn-affil= affil-num=32 en-affil=Biosciences Institute, Newcastle University kn-affil= affil-num=33 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=34 en-affil=Department of Anatomical Sciences, School of Medicine, St. George's University kn-affil= affil-num=35 en-affil=Department of Neurosurgery, Tulane University School of Medicine kn-affil= en-keyword=anatomy kn-keyword=anatomy en-keyword=cadaver kn-keyword=cadaver en-keyword=commercial kn-keyword=commercial en-keyword=consent kn-keyword=consent en-keyword=dissection kn-keyword=dissection en-keyword=donors kn-keyword=donors en-keyword=medical education kn-keyword=medical education en-keyword=medical ethics kn-keyword=medical ethics en-keyword=publishing kn-keyword=publishing END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=489 end-page=492 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=Favorable outcomes of epilepsy with gait-induced seizures after resection of the unilateral supplementary motor area en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Gait-induced seizures are a rare manifestation of reflex epilepsy. Pathophysiology of this phenomenon has not been fully understood.
Case presentation: A 28-year-old woman presented with a long history of gfallsh following paroxysmal bilateral leg stiffness triggered by walking. Scalp electroencephalogram (EEG) revealed low-amplitude rhythmic beta activity, maximal at the Cz electrode, during these events. Magnetoencephalography demonstrated repetitive sharp waves source-localized to the right primary motor cortex. Multiple anti-seizure medications failed to improve her symptoms; however, the clinical manifestation was consistent with epilepsy with gait-induced seizures. Intracranial subdural EEG recording was performed and confirmed ictal activity originating from the right supplementary motor area. Resection of this area resulted in complete resolution of her symptoms.
Discussion: This is the first reported case of successful resective surgery for epilepsy with gait-induced seizure. Brain networks involving cortical regions responsible for the initiation or execution of walking presumably played a key role in the generation of gait-induced seizures. Careful assessment using non-invasive neurophysiological studies facilitated accurate diagnosis, successful intracranial recordings, and effective resective surgery. en-copyright= kn-copyright= en-aut-name=KodamaSatoshi en-aut-sei=Kodama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuniiNaoto en-aut-sei=Kunii en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShirotaYuichiro en-aut-sei=Shirota en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChouTakusei en-aut-sei=Chou en-aut-mei=Takusei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiMizuho en-aut-sei=Kawai en-aut-mei=Mizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimadaSeijiro en-aut-sei=Shimada en-aut-mei=Seijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaedaMeiko en-aut-sei=Maeda en-aut-mei=Meiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=HamadaMasashi en-aut-sei=Hamada en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IkemuraMasako en-aut-sei=Ikemura en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaitoYuko en-aut-sei=Saito en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AkamatsuNaoki en-aut-sei=Akamatsu en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UeharaTaira en-aut-sei=Uehara en-aut-mei=Taira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SaitoNobuhito en-aut-sei=Saito en-aut-mei=Nobuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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 Neurosurgery, Jichi Medical University kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Pathology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Neuropahtology (Brain Bank for Aging Research), Tokyo Metropoliran Institute for Geriatrics and Gerontology kn-affil= affil-num=12 en-affil=Department of Neurology, International University of Health and Walfare Narita Hospital kn-affil= affil-num=13 en-affil=Department of Neurology, International University of Health and Walfare Narita Hospital kn-affil= affil-num=14 en-affil=Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=15 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= en-keyword=Reflex epilepsy kn-keyword=Reflex epilepsy en-keyword=Intracranial electroencephalogram (EEG) kn-keyword=Intracranial electroencephalogram (EEG) en-keyword=Electrocorticogram kn-keyword=Electrocorticogram en-keyword=magnetoencephalogram (MEG) kn-keyword=magnetoencephalogram (MEG) en-keyword=SMA kn-keyword=SMA END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=13 article-no= start-page=1863 end-page=1872 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Activated CD4+ T Cell Proportion in the Peripheral Blood Correlates with the Duration of Cytokine Release Syndrome and Predicts Clinical Outcome after Chimeric Antigen Receptor T Cell Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Chimeric antigen receptor (CAR) T cell therapy is an emerging and effective therapy for relapsed or refractory diffuse large B cell lymphoma (R/R DLBCL). The characteristic toxicities of CAR T cell therapy include cytokine release syndrome (CRS) and prolonged cytopenia. We investigated the factors associated with these complications after CAR T cell therapy by analyzing lymphocyte subsets following CAR T cell infusion.
Methods We retrospectively analyzed peripheral blood samples on days 7, 14, and 28 after tisagenlecleucel (tisa-cel) infusion by flow cytometry at our institution between June 2020 and September 2022.
Patients Thirty-five patients with R/R DLBCL who received tisa-cel therapy were included.
Results A flow cytometry-based analysis of blood samples from these patients revealed that the proportion of CD4+CD25+CD127+ T cells (hereafter referred to as "activated CD4+ T cells" ) among the total CD4+ T cells on day 7 after tisa-cel infusion correlated with the duration of CRS (r=0.79, p<0.01). In addition, a prognostic analysis of the overall survival (OS) using time-dependent receiver operating characteristic curves indicated a significantly more favorable OS and progression-free survival of patients with a proportion of activated CD4+ T cells among the total CD4+ T cells <0.73 (p=0.01, and p<0.01, respectively).
Conclusion These results suggest that the proportion of activated CD4+ T cells on day 7 after tisa-cel infusion correlates with the CRS duration and predicts clinical outcomes after CAR T cell therapy. Further studies with a larger number of patients are required to validate these observations. en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkegawaShuntaro en-aut-sei=Ikegawa en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamoiChihiro en-aut-sei=Kamoi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= 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=10 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Japan kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=9 en-affil=Division of Blood Transfusion, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=chimeric antigen receptor T cell therapy kn-keyword=chimeric antigen receptor T cell therapy en-keyword=diffuse large B cell lymphoma kn-keyword=diffuse large B cell lymphoma en-keyword=flow cytometry kn-keyword=flow cytometry en-keyword=cytokine release syndrome kn-keyword=cytokine release syndrome en-keyword=prolonged cytopenia kn-keyword=prolonged cytopenia END start-ver=1.4 cd-journal=joma no-vol=194 cd-vols= no-issue= article-no= start-page=50 end-page=62 dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Increasing visual uncertainty modulates multisensory decision-making en-subtitle= kn-subtitle= en-abstract= kn-abstract=The brain integrates and transforms information from multiple senses to make optimal decisions, a process that is critical for navigating complex environments with perceptual uncertainty. Despite a growing consensus that individuals adapt flexibly to uncertain sensory input, whether increasing visual uncertainty influences the decision process itself or other, non-decision sensory processes during multisensory decision-making are unclear. Here, an audiovisual categorization task was used to examine the responses of human participants (N = 30) to visual and audiovisual stimuli under low-, medium-, and high-uncertainty conditions. Modeling the behavioral data using a drift?diffusion model indicated that increased visual uncertainty in the audiovisual context decreased the evidence accumulation rate but had no effect on non-decision processes. Electrophysiological recordings confirmed and expanded upon these results: increased visual uncertainty in the audiovisual context reduced the amplitude during the late decision-making stage (300?380 msec) but had no effect on the amplitude during the early sensory encoding stage (140?220 msec). More importantly, electroencephalography analyses revealed that audiovisual integration in the early sensory encoding stage occurred robustly across all visual uncertainty conditions, whereas audiovisual integration in the late stage occurred only under medium and high visual uncertainty conditions. This study demonstrated that increased visual uncertainty modulates the decision process itself rather than early sensory encoding during multisensory decision-making. Moreover, multisensory integration strategies dynamically adapt to increasing visual uncertainty by engaging different mechanisms to maintain effective decision-making. en-copyright= kn-copyright= en-aut-name=YangXiangfu en-aut-sei=Yang en-aut-mei=Xiangfu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YangWeiping en-aut-sei=Yang en-aut-mei=Weiping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Psychology, Faculty of Education, Hubei University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Multisensory decision-making kn-keyword=Multisensory decision-making en-keyword=Visual uncertainty kn-keyword=Visual uncertainty en-keyword=Audiovisual integration kn-keyword=Audiovisual integration en-keyword=Event-related potential kn-keyword=Event-related potential en-keyword=Drift?diffusion model kn-keyword=Drift?diffusion model END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=4 article-no= start-page=e70051 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Interaction between nuclear]translocated cellular communication network factor 2 and purine]rich box 1 regulates the expression of fibrosis]related genes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cellular communication network factor 2 (CCN2) with a nuclear localization signal-like peptide is known to promote fibrosis. However, translocation of CCN2 into the nucleus and its role in fibrosis remain unclear. We hypothesized that nuclear-translocated CCN2 is associated with purine-rich box 1 (PU.1), which is a transcription factor regulating the differentiation of myofibroblasts. Western blot analysis of the cytoplasmic and nuclear fractions of cell lysate and immunofluorescence analysis revealed that CCN2 was detectable in both the cytoplasm and nuclei of murine fibroblastic NIH3T3 cells. Additionally, chromatin immunoprecipitation (IP)-PCR and an electrophoretic mobility shift assay revealed that recombinant CCN2 protein bound to the regulatory region of Spi1, which encodes PU.1. Furthermore, IP-Western blot analysis showed that CCN2 interacted with PU.1. Finally, the forced expression of both Ccn2 and Spi1 significantly promoted the production of angiotensin II, and increased fibrosis-related molecules, such as Col1a1 and Acta2, at the gene and protein levels. These findings indicate that CCN2 translocated to the nucleus interacts with PU.1 and that the complex promotes the markers of myofibroblast differentiation, suggesting that CCN2 plays an important role in fibrosis via cooperation with PU.1, as a transcription co-factor. en-copyright= kn-copyright= en-aut-name=NguyenXuan Thi en-aut-sei=Nguyen en-aut-mei=Xuan Thi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=NishidaTakashi en-aut-sei=Nishida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan kn-affil= affil-num=4 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cellular communication network factor 2 (CCN2) kn-keyword=cellular communication network factor 2 (CCN2) en-keyword=fibrosis kn-keyword=fibrosis en-keyword=myofibroblast kn-keyword=myofibroblast en-keyword=purine]rich box 1 (PU.1) kn-keyword=purine]rich box 1 (PU.1) en-keyword=transcription co]factor kn-keyword=transcription co]factor END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=4 article-no= start-page=e70082 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Retinopathy?Sensory Neuropathy Syndrome With a Novel Compound Heterozygous FLVCR1 Variant en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aims: Retinopathy?sensory neuropathy syndrome (RETSNS), also known as posterior column ataxia with retinitis pigmentosa (PCARP), is a rare neurodegenerative disorder that is caused by biallelic pathogenic variants in FLVCR1. Here, we report a case of a Japanese patient with RETSNS.
Methods: Clinical, neuroradiological, and electrophysiological findings were documented. Whole-genome sequencing was performed. Subcloning was carried out to confirm compound heterozygosity. A functional assay was performed to assess the pathogenicity of the variants.
Results: The patient showed retinitis pigmentosa and sensory ataxia. Over the course of the disease, autonomic dysfunction has become increasingly evident. Despite consanguinity in the family, whole-genome sequencing identified two heterozygous variants in FLVCR1 (c.369T>G, p.Phe123Leu and c.733A>G, p.Asn245Asp). Cloning of the PCR product followed by Sanger sequencing indicated compound heterozygosity of the variants. Immunocytochemistry of HEK293FT cells transfected with plasmids containing wild-type or variant FLVCR1 cDNA demonstrated altered subcellular localization of the variant FLVCR1 proteins, characterized by reduced membrane localization.
Interpretation: We report a novel variant in FLVCR1 causing RETSNS. The functional assay supports the pathogenicity of the variants. en-copyright= kn-copyright= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanoTomohito en-aut-sei=Kawano en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TairaYuki en-aut-sei=Taira en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuoAyaka en-aut-sei=Matsuo en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=YunokiTaijun en-aut-sei=Yunoki en-aut-mei=Taijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NomuraEmi en-aut-sei=Nomura en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama City General Medical Center kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=FLCVR1 kn-keyword=FLCVR1 en-keyword=functional analysis kn-keyword=functional analysis en-keyword=posterior column ataxia with retinitis pigmentosa kn-keyword=posterior column ataxia with retinitis pigmentosa en-keyword=subcellular localization kn-keyword=subcellular localization END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=2 article-no= start-page=25-00212 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=DNS analysis on the correlation between local burning velocity and flame displacement speed of turbulent premixed flames en-subtitle= kn-subtitle= en-abstract= kn-abstract=The local burning velocity and flame displacement speed are the major properties of premixed flames. The local burning velocity, which is the instantaneous quantity based on the local consumption rate of the unburnt mixture, is considered to be the most appropriate burning velocity in terms of the definition. The local burning velocity can be evaluated theoretically and numerically; however, it is almost impossible to obtain it experimentally using the current technology of measurement. The flame displacement speed can be evaluated more easily than the local burning velocity and compared with the flame displacement speed obtained from experiments. However, the local burning velocity and flame displacement speed have been discussed separately in turbulent premixed flames. In this study, to clarify the relation between the local burning velocity and the flame displacement speed, numerical analyses were performed using the DNS database of statistically steady and fully developed turbulent premixed flames with different density ratios of the unburnt mixture to the burnt product and with different Lewis numbers. It was found that for different density ratios, the local burning velocity was little sensitive to the flame displacement speed in any case under the unity Lewis number. This means the correlation between the local burning velocity and the flame displacement speed is little affected by the dilation of a flame. For different Lewis numbers, the correlation between the local burning velocity and the flame displacement speed was negative in Le = 0.8, and positive in Le = 1.2. This can be explained by the effect of the Lewis number on the local burning velocity, and the flame displacement speed was little affected by the Lewis number in the correlation between the local burning velocity and the flame displacement speed. en-copyright= kn-copyright= en-aut-name=TSUBOIKazuya en-aut-sei=TSUBOI en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Direct Numerical Simulation (DNS) kn-keyword=Direct Numerical Simulation (DNS) en-keyword=Turbulent premixed flame kn-keyword=Turbulent premixed flame en-keyword=Local burning velocity kn-keyword=Local burning velocity en-keyword=Flame displacement speed kn-keyword=Flame displacement speed en-keyword=Density ratio kn-keyword=Density ratio en-keyword=Dilation kn-keyword=Dilation en-keyword=Lewis number kn-keyword=Lewis number END start-ver=1.4 cd-journal=joma no-vol=992 cd-vols= no-issue=1 article-no= start-page=27 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251003 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Observing Supernova Neutrino Light Curves with Super-Kamiokande. VI. A Practical Data Analysis Technique Considering Realistic Experimental Backgrounds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neutrinos from supernovae, especially those emitted during the late phase of core collapse, are essential for understanding the final stages of massive star evolution. We have been dedicated to developing methods for the analysis of neutrinos emitted during the late phase and observed at Super-Kamiokande (SK). Our previous studies have successfully demonstrated the potential of various analysis methods in extracting essential physical properties; however, the lack of background consideration has limited their practical application. In this study, we address this issue by incorporating a realistic treatment of the experimental signal and background events with the on-going SK experiment. We therefore optimize our analysis framework to reflect realistic observational conditions, including both signal and background events. Using this framework we study several long-time supernova models, simulating the late phase neutrino observation in SK and focusing in particular on the identification of the last observed event. We discuss the possibility of model discrimination methods using timing information from this last observed event. en-copyright= kn-copyright= en-aut-name=NakanishiFumi en-aut-sei=Nakanishi en-aut-mei=Fumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakazatoKenfichiro en-aut-sei=Nakazato en-aut-mei=Kenfichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaMasayuki en-aut-sei=Harada en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KoshioYusuke en-aut-sei=Koshio en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkahoRyuichiro en-aut-sei=Akaho en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AshidaYosuke en-aut-sei=Ashida en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaradaAkira en-aut-sei=Harada en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoriMasamitsu en-aut-sei=Mori en-aut-mei=Masamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SumiyoshiKohsuke en-aut-sei=Sumiyoshi en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SuwaYudai en-aut-sei=Suwa en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WendellRoger A. en-aut-sei=Wendell en-aut-mei=Roger A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ZaizenMasamichi en-aut-sei=Zaizen en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Physics, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Arts and Science, Kyushu University kn-affil= affil-num=3 en-affil=Kamioka Observatory, Institute for Cosmic Ray Research, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Physics, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Science and Engineering, Waseda University kn-affil= affil-num=6 en-affil=Department of Physics, Tohoku University kn-affil= affil-num=7 en-affil=National Institute of Technology, Ibaraki College kn-affil= affil-num=8 en-affil=Division of Science, National Astronomical Observatory of Japan kn-affil= affil-num=9 en-affil=National Institute of Technology, Numazu College kn-affil= affil-num=10 en-affil=Department of Earth Science and Astronomy, The University of Tokyo kn-affil= affil-num=11 en-affil=Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU, WPI), Todai Institutes for Advanced Study, The University of Tokyo kn-affil= affil-num=12 en-affil=Department of Earth Science and Astronomy, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=469 end-page=474 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ileus Tube-Related Intussusception: A Case Report and Review of 80 Previously Reported Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a rare case of ileus tube-related intussusception in an adult. A 56-year-old man with adhesive bowel obstruction was treated with a nasointestinal ileus tube. Although his condition initially improved, persistent abdominal pain led to the diagnosis of intussusception via CT imaging. Manual repositioning of the tube resolved the intussusception without the need for bowel resection. A review of 80 previously reported cases of ileus tube-associated intussusception (total 81 cases, 95 lesions) highlighted the timing of onset, treatment strategies, and precautions. Early detection and diagnosis are crucial to prevent severe complications and preserve bowel function. en-copyright= kn-copyright= en-aut-name=TsujiiTeruyuki en-aut-sei=Tsujii en-aut-mei=Teruyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsudaTatsuo en-aut-sei=Matsuda en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraYuji en-aut-sei=Kimura en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsubeRyoichi en-aut-sei=Katsube en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwadouHironori en-aut-sei=Iwadou en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FunabikiSadami en-aut-sei=Funabiki en-aut-mei=Sadami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamikawaYasuaki en-aut-sei=Kamikawa en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsudaTadakazu en-aut-sei=Matsuda en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=6 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Matsuda Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Matsuda Hospital kn-affil= en-keyword=nasointestinal ileus tube kn-keyword=nasointestinal ileus tube en-keyword=intussusception kn-keyword=intussusception en-keyword=small bowel obstruction kn-keyword=small bowel obstruction en-keyword=enterectomy kn-keyword=enterectomy en-keyword=conservative treatment kn-keyword=conservative treatment END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=463 end-page=468 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MRI Images of a Case of Adenocarcinoma, Human Papillomavirus-Independent, Mesonephric Type, of the Uterine Cervix en-subtitle= kn-subtitle= en-abstract= kn-abstract=We present a case of a woman in her 70s who was diagnosed with mesonephric adenocarcinoma of the uterine cervix, following biopsy and surgery. Preoperative MRI revealed a 7-cm, well-defined circumferential cervical mass with left lateral wall predominance, bulging into the uterine cavity and vagina. The lesion showed intermediate signal intensity on T2-weighted images, diffusion restriction, and early contrast enhancement weaker than that of the myometrium, followed by washout on contrast-enhanced imaging. The circumferential growth pattern with the lateral wall predominance and its imaging characteristics may suggest this rare entity be routinely included in the differential diagnosis of cervical cancers. en-copyright= kn-copyright= en-aut-name=AsanoYudai en-aut-sei=Asano en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiharaChika en-aut-sei=Nishihara en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KitayamaTakahiro en-aut-sei=Kitayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkawaNanako en-aut-sei=Okawa en-aut-mei=Nanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakimotoSatoko en-aut-sei=Makimoto en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigakiFumiyo en-aut-sei=Higaki en-aut-mei=Fumiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=SugiharaHanako en-aut-sei=Sugihara en-aut-mei=Hanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IdaNaoyuki en-aut-sei=Ida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=mesonephric adenocarcinoma kn-keyword=mesonephric adenocarcinoma en-keyword=cervical cancer kn-keyword=cervical cancer en-keyword=MRI imaging characteristics kn-keyword=MRI imaging characteristics en-keyword=HPV-independent adenocarcinoma kn-keyword=HPV-independent adenocarcinoma END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=451 end-page=455 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recurrence of FVIII Inhibitor during Surgery in a Patient with Severe Hemophilia A Receiving Emicizumab Prophylaxis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Emicizumab, a bispecific monoclonal antibody, benefits patients with severe hemophilia A. It alters laboratory assessments of coagulation activity, requiring anti-idiotype monoclonal antibodies for accurate monitoring. A 64-year-old man, receiving emicizumab regularly, was admitted for laminoplasty. We planned to use FVIII replacement during the perioperative period after confirming the disappearance of inhibitors, monitoring coagulation activity with anti-idiotype monoclonal antibodies. Activated partial thromboplastin time was prolonged on postoperative day 2, prompting an immediate switch to eptacog alfa. The patient recovered without bleeding. This case underscores the necessity of anti-idiotype monoclonal antibodies for accurate monitoring. en-copyright= kn-copyright= en-aut-name=HagiharaMoe en-aut-sei=Hagihara en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HayashinoKenta en-aut-sei=Hayashino en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KinKyohei en-aut-sei=Kin en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=emicizumab kn-keyword=emicizumab en-keyword=eptacog alfa kn-keyword=eptacog alfa en-keyword=hemophilia A kn-keyword=hemophilia A en-keyword=inhibitor kn-keyword=inhibitor en-keyword=anti-idiotype monoclonal antibodies to emicizumab kn-keyword=anti-idiotype monoclonal antibodies to emicizumab END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=437 end-page=444 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Frailty at 1 Month before ICU Admission Poses a Hospital Mortality Risk in Cancer Survivors whose Condition Has Deteriorated due to Medical Factors en-subtitle= kn-subtitle= en-abstract= kn-abstract=The optimal indications for intensive care unit (ICU) treatment for critically ill cancer survivors whose condition has deteriorated due to medical factors are unclear. To test our hypothesis that frailty before deterioration was associated with hospital mortality in this patient population, we retrospective analyzed the cases of the patients admitted to the ICU at the National Cancer Center Hospital, Japan (April 2014-March 2022). We excluded patients who underwent surgery within 28 days or were denied critical care within 24 h or admitted after cardiopulmonary arrest. Their Clinical Frailty Scale (CFS) scores at 1 month before ICU admission (Pre-ICU) were obtained. Frailty was defined as CFS scores ?4 points. We analyzed 298 admissions and observed that the mortality rate at hospital discharge was significantly higher in the frailty group (n=119). A multivariate analysis demonstrated that the following factors were significantly associated with hospital mortality: Pre-ICU frailty (OR 2.00, 95%CI: 1.19-3.36, p=0.009), cancer type (hematological: OR 2.93, 95%CI: 1.42-6.05, p=0.004), and Sequential Organ Failure Assessment score at ICU admission (OR 0.88, 95%CI: 0.82-0.95, p=0.0008). Frailty retrospectively assessed using the CFS at 1 month pre-ICU admission is a risk factor for hospital mortality in these cancer survivors. 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=SatoTetsufumi en-aut-sei=Sato en-aut-mei=Tetsufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Intensive Care Medicine, National Cancer Center Hospital kn-affil= en-keyword=frailty kn-keyword=frailty en-keyword=cancer survivor kn-keyword=cancer survivor en-keyword=clinical frailty scale kn-keyword=clinical frailty scale en-keyword=cancer kn-keyword=cancer en-keyword=critically ill kn-keyword=critically ill END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=421 end-page=429 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Thoron Inhalation and Cyclosporin A Treatment on Dextran Sulfate Sodium-Induced Oxidative Damage in Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Radon (222Rn; Rn) and thoron (220Rn; Tn) inhalation have been reported to enhance antioxidant activity in various organs. However, the effects of Tn on the colon have not been investigated. This study aimed to clarify the effects of Tn inhalation, alone and in combination with cyclosporin A (CsA), on dextran sulfate sodium (DSS)-induced colitis, and the accompanying oxidative stress, in mice. Male BALB/c mice were subjected to continuous 8-day Tn inhalation (c-Tn, 533}128 Bq/m3) or alternate-day Tn inhalation over the same period (f-Tn, 577}63Bq/m3), followed by treatment with 3% DSS and either CsA or vehicle for 7 days. Although the disease activity index (DAI) decreased significantly by day 2 in the c-Tn group, scores remained significantly higher than those in the f-Tn group. In the c-Tn group, superoxide dismutase and catalase activity in the colon were significantly elevated compared with those in sham controls. Thus, DSS-induced damage was effectively inhibited in the earlier stages by the c-Tn mode of inhalation than by the f-Tn mode. These findings suggest that continuous Tn inhalation more effectively attenuated early colitis symptoms than alternate-day inhalation, potentially through upregulation of antioxidant defenses. Tn and CsA showed no combined effects. en-copyright= kn-copyright= en-aut-name=TanakaAyumi en-aut-sei=Tanaka en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaoeShota en-aut-sei=Naoe en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakenakaReiju en-aut-sei=Takenaka en-aut-mei=Reiju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanzakiNorie en-aut-sei=Kanzaki en-aut-mei=Norie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakodaAkihiro en-aut-sei=Sakoda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamaokaKiyonori en-aut-sei=Yamaoka en-aut-mei=Kiyonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KataokaTakahiro en-aut-sei=Kataoka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=5 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=6 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Health Sciences, Okayama University kn-affil= en-keyword=thoron kn-keyword=thoron en-keyword=DSS kn-keyword=DSS en-keyword=antioxidant activity kn-keyword=antioxidant activity en-keyword=CsA kn-keyword=CsA en-keyword=colon kn-keyword=colon END